Neuroproteomics pp 65-99

Part of the Methods in Molecular Biology book series (MIMB, volume 1598) | Cite as

Degradomics in Neurotrauma: Profiling Traumatic Brain Injury

  • Hadi Abou-El-Hassan
  • Fares Sukhon
  • Edwyn Jeremy Assaf
  • Hisham Bahmad
  • Hussein Abou-Abbass
  • Hussam Jourdi
  • Firas H. Kobeissy
Protocol

Abstract

Degradomics has recently emerged as a subdiscipline in the omics era with a focus on characterizing signature breakdown products implicated in various disease processes. Driven by promising experimental findings in cancer, neuroscience, and metabolomic disorders, degradomics has significantly promoted the notion of disease-specific “degradome.” A degradome arises from the activation of several proteases that target specific substrates and generate signature protein fragments. Several proteases such as calpains, caspases, cathepsins, and matrix metalloproteinases (MMPs) are involved in the pathogenesis of numerous diseases that disturb the physiologic balance between protein synthesis and protein degradation. While regulated proteolytic activities are needed for development, growth, and regeneration, uncontrolled proteolysis initiated under pathological conditions ultimately culminates into apoptotic and necrotic processes. In this chapter, we aim to review the protease-substrate repertoires in neural injury concentrating on traumatic brain injury. A striking diversity of protease substrates, essential for neuronal and brain structural and functional integrity, namely, encryptic biomarker neoproteins, have been characterized in brain injury. These include cytoskeletal proteins, transcription factors, cell cycle regulatory proteins, synaptic proteins, and cell junction proteins. As these substrates are subject to proteolytic fragmentation, they are ceaselessly exposed to activated proteases. Characterization of these molecules allows for a surge of “possible” therapeutic approaches of intervention at various levels of the proteolytic cascade.

Key words

Degradomics Degradome Degradation Proteolysis Breakdown Biomarkers Protease Calpain Caspase Big data Brain Trauma Injury 

References

  1. 1.
    McQuibban GA, Gong JH, Tam EM, McCulloch CA, Clark-Lewis I, Overall CM (2000) Inflammation dampened by gelatinase A cleavage of monocyte chemoattractant protein-3. Science 289:1202–1206PubMedCrossRefGoogle Scholar
  2. 2.
    Lee AY, Park BC, Jang M, Cho S, Lee DH, Lee SC, Myung PK, Park SG (2004) Identification of caspase-3 degradome by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight analysis. Proteomics 4:3429–3436PubMedCrossRefGoogle Scholar
  3. 3.
    Lopez-Otin C, Overall CM (2002) Protease degradomics: a new challenge for proteomics. Nat Rev Mol Cell Biol 3:509–519PubMedCrossRefGoogle Scholar
  4. 4.
    Yu Y, Prassas I, Dimitromanolakis A, Diamandis EP (2015) Novel biological substrates of human kallikrein 7 identified through degradomics. J Biol Chem 290:17762–17775PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Butler GS, Overall CM (2009) Updated biological roles for matrix metalloproteinases and new “intracellular” substrates revealed by degradomics. Biochemistry 48:10830–10845PubMedCrossRefGoogle Scholar
  6. 6.
    Plasman K, Maurer-Stroh S, Gevaert K, Van Damme P (2014) Holistic view on the extended substrate specificities of orthologous granzymes. J Proteome Res 13:1785–1793PubMedCrossRefGoogle Scholar
  7. 7.
    Wang KK (2000) Calpain and caspase: can you tell the difference? Trends Neurosci 23:20–26PubMedCrossRefGoogle Scholar
  8. 8.
    Rawlings ND, Barrett AJ, Finn R (2016) Twenty years of the MEROPS database of proteolytic enzymes, their substrates and inhibitors. Nucleic Acids Res 44:D343–D350PubMedCrossRefGoogle Scholar
  9. 9.
    Turk B (2006) Targeting proteases: successes, failures and future prospects. Nat Rev Drug Discov 5:785–799PubMedCrossRefGoogle Scholar
  10. 10.
    Turk B, Turk D, Turk V (2012) Protease signalling: the cutting edge. EMBO J 31:1630–1643PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Kobeissy FH, Sadasivan S, Liu J, Gold MS, Wang KK (2008) Psychiatric research: psychoproteomics, degradomics and systems biology. Expert Rev Proteomics 5:293–314PubMedCrossRefGoogle Scholar
  12. 12.
    Kim JH, Kwon SJ, Stankewich MC, Huh GY, Glantz SB, Morrow JS (2016) Reactive protoplasmic and fibrous astrocytes contain high levels of calpain-cleaved alpha 2 spectrin. Exp Mol Pathol 100:1–7PubMedCrossRefGoogle Scholar
  13. 13.
    Du J, Wang X, Miereles C, Bailey JL, Debigare R, Zheng B, Price SR, Mitch WE (2004) Activation of caspase-3 is an initial step triggering accelerated muscle proteolysis in catabolic conditions. J Clin Invest 113:115–123PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Brana C, Benham CD, Sundstrom LE (1999) Calpain activation and inhibition in organotypic rat hippocampal slice cultures deprived of oxygen and glucose. Eur J Neurosci 11:2375–2384PubMedCrossRefGoogle Scholar
  15. 15.
    Trindade F, Ferreira R, Amado F, Vitorino R (2015) Biofluid proteases profiling in diabetes mellitus. Adv Clin Chem 69:161–207PubMedCrossRefGoogle Scholar
  16. 16.
    Agard NJ, Wells JA (2009) Methods for the proteomic identification of protease substrates. Curr Opin Chem Biol 13:503–509PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Doucet A, Butler GS, Rodriguez D, Prudova A, Overall CM (2008) Metadegradomics: toward in vivo quantitative degradomics of proteolytic post-translational modifications of the cancer proteome. Mol Cell Proteomics 7:1925–1951PubMedCrossRefGoogle Scholar
  18. 18.
    Overall CM, Dean RA (2006) Degradomics: systems biology of the protease web. Pleiotropic roles of MMPs in cancer. Cancer Metastasis Rev 25:69–75PubMedCrossRefGoogle Scholar
  19. 19.
    Overall CM, Tam EM, Kappelhoff R, Connor A, Ewart T, Morrison CJ, Puente X, Lopez-Otin C, Seth A (2004) Protease degradomics: mass spectrometry discovery of protease substrates and the CLIP-CHIP, a dedicated DNA microarray of all human proteases and inhibitors. Biol Chem 385:493–504PubMedCrossRefGoogle Scholar
  20. 20.
    Vizovisek M, Vidmar R, Fonovic M, Turk B (2016) Current trends and challenges in proteomic identification of protease substrates. Biochimie 122:77–87PubMedCrossRefGoogle Scholar
  21. 21.
    van den Berg BH, Tholey A (2012) Mass spectrometry-based proteomics strategies for protease cleavage site identification. Proteomics 12:516–529PubMedCrossRefGoogle Scholar
  22. 22.
    van den Broek I, Sparidans RW, Schellens JH, Beijnen JH (2010) Quantitative assay for six potential breast cancer biomarker peptides in human serum by liquid chromatography coupled to tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 878:590–602PubMedCrossRefGoogle Scholar
  23. 23.
    Impens F, Colaert N, Helsens K, Plasman K, Van Damme P, Vandekerckhove J, Gevaert K (2010) MS-driven protease substrate degradomics. Proteomics 10:1284–1296PubMedCrossRefGoogle Scholar
  24. 24.
    van Domselaar R, de Poot SA, Bovenschen N (2010) Proteomic profiling of proteases: tools for granzyme degradomics. Expert Rev Proteomics 7:347–359PubMedCrossRefGoogle Scholar
  25. 25.
    Doucet A, Overall CM (2008) Protease proteomics: revealing protease in vivo functions using systems biology approaches. Mol Aspects Med 29:339–358PubMedCrossRefGoogle Scholar
  26. 26.
    Patterson NL, Iyer RP, de Castro Bras LE, Li Y, Andrews TG, Aune GJ, Lange RA, Lindsey ML (2013) Using proteomics to uncover extracellular matrix interactions during cardiac remodeling. Proteomics Clin Appl 7:516–527PubMedCrossRefGoogle Scholar
  27. 27.
    Zamilpa R, Lopez EF, Chiao YA, Dai Q, Escobar GP, Hakala K, Weintraub ST, Lindsey ML (2010) Proteomic analysis identifies in vivo candidate matrix metalloproteinase-9 substrates in the left ventricle post-myocardial infarction. Proteomics 10:2214–2223PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Mukherjee R, Snipes JM, Saunders SM, Zavadzkas JA, Spinale FG (2012) Discordant activation of gene promoters for matrix metalloproteinases and tissue inhibitors of the metalloproteinases following myocardial infarction. J Surg Res 172:59–67PubMedCrossRefGoogle Scholar
  29. 29.
    Lindsey ML, Zamilpa R (2012) Temporal and spatial expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases following myocardial infarction. Cardiovasc Ther 30:31–41PubMedCrossRefGoogle Scholar
  30. 30.
    Lauhio A, Farkkila E, Pietilainen KH, Astrom P, Winkelmann A, Tervahartiala T, Pirila E, Rissanen A, Kaprio J, Sorsa TA, Salo T (2016) Association of MMP-8 with obesity, smoking and insulin resistance. Eur J Clin Invest 46(9):757–765PubMedCrossRefGoogle Scholar
  31. 31.
    Riddick AC, Shukla CJ, Pennington CJ, Bass R, Nuttall RK, Hogan A, Sethia KK, Ellis V, Collins AT, Maitland NJ, Ball RY, Edwards DR (2005) Identification of degradome components associated with prostate cancer progression by expression analysis of human prostatic tissues. Br J Cancer 92:2171–2180PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Noel A, Jost M, Maquoi E (2008) Matrix metalloproteinases at cancer tumor-host interface. Semin Cell Dev Biol 19:52–60PubMedCrossRefGoogle Scholar
  33. 33.
    Egeblad M, Werb Z (2002) New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2:161–174PubMedCrossRefGoogle Scholar
  34. 34.
    van Winden AW, van den Broek I, Gast MC, Engwegen JY, Sparidans RW, van Dulken EJ, Depla AC, Cats A, Schellens JH, Peeters PH, Beijnen JH, van Gils CH (2010) Serum degradome markers for the detection of breast cancer. J Proteome Res 9:3781–3788PubMedCrossRefGoogle Scholar
  35. 35.
    Villanueva J, Shaffer DR, Philip J, Chaparro CA, Erdjument-Bromage H, Olshen AB, Fleisher M, Lilja H, Brogi E, Boyd J, Sanchez-Carbayo M, Holland EC, Cordon-Cardo C, Scher HI, Tempst P (2006) Differential exoprotease activities confer tumor-specific serum peptidome patterns. J Clin Invest 116:271–284PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Kowluru RA, Zhong Q, Santos JM (2012) Matrix metalloproteinases in diabetic retinopathy: potential role of MMP-9. Expert Opin Investig Drugs 21:797–805PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Choi J, Lin A, Shrier E, Lau LF, Grant MB, Chaqour B (2013) Degradome products of the matricellular protein CCN1 as modulators of pathological angiogenesis in the retina. J Biol Chem 288:23075–23089PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Hadler-Olsen E, Winberg JO, Reinholt FP, Larsen T, Uhlin-Hansen L, Jenssen T, Berg E, Kolset SO (2011) Proteases in plasma and kidney of db/db mice as markers of diabetes-induced nephropathy. ISRN Endocrinol 2011:832642PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Korpos E, Kadri N, Kappelhoff R, Wegner J, Overall CM, Weber E, Holmberg D, Cardell S, Sorokin L (2013) The peri-islet basement membrane, a barrier to infiltrating leukocytes in type 1 diabetes in mouse and human. Diabetes 62:531–542PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Ren RJ, Dammer EB, Wang G, Seyfried NT, Levey AI (2014) Proteomics of protein post-translational modifications implicated in neurodegeneration. Transl Neurodegener 3:23PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Kleifeld O, Doucet A, auf dem Keller U, Prudova A, Schilling O, Kainthan RK, Starr AE, Foster LJ, Kizhakkedathu JN, Overall CM (2010) Isotopic labeling of terminal amines in complex samples identifies protein N-termini and protease cleavage products. Nat Biotechnol 28:281–288PubMedCrossRefGoogle Scholar
  42. 42.
    Bains M, Cebak JE, Gilmer LK, Barnes CC, Thompson SN, Geddes JW, Hall ED (2013) Pharmacological analysis of the cortical neuronal cytoskeletal protective efficacy of the calpain inhibitor SNJ-1945 in a mouse traumatic brain injury model. J Neurochem 125:125–132PubMedCrossRefGoogle Scholar
  43. 43.
    Thompson SN, Carrico KM, Mustafa AG, Bains M, Hall ED (2010) A pharmacological analysis of the neuroprotective efficacy of the brain- and cell-permeable calpain inhibitor MDL-28170 in the mouse controlled cortical impact traumatic brain injury model. J Neurotrauma 27:2233–2243PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Knoblach SM, Alroy DA, Nikolaeva M, Cernak I, Stoica BA, Faden AI (2004) Caspase inhibitor z-DEVD-fmk attenuates calpain and necrotic cell death in vitro and after traumatic brain injury. J Cereb Blood Flow Metab 24:1119–1132PubMedCrossRefGoogle Scholar
  45. 45.
    Kupina NC, Nath R, Bernath EE, Inoue J, Mitsuyoshi A, Yuen PW, Wang KK, Hall ED (2001) The novel calpain inhibitor SJA6017 improves functional outcome after delayed administration in a mouse model of diffuse brain injury. J Neurotrauma 18:1229–1240PubMedCrossRefGoogle Scholar
  46. 46.
    Posmantur R, Kampfl A, Siman R, Liu J, Zhao X, Clifton GL, Hayes RL (1997) A calpain inhibitor attenuates cortical cytoskeletal protein loss after experimental traumatic brain injury in the rat. Neuroscience 77:875–888PubMedCrossRefGoogle Scholar
  47. 47.
    Saatman KE, Murai H, Bartus RT, Smith DH, Hayward NJ, Perri BR, McIntosh TK (1996) Calpain inhibitor AK295 attenuates motor and cognitive deficits following experimental brain injury in the rat. Proc Natl Acad Sci U S A 93:3428–3433PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Zhang Z, Larner SF, Liu MC, Zheng W, Hayes RL, Wang KK (2009) Multiple alphaII-spectrin breakdown products distinguish calpain and caspase dominated necrotic and apoptotic cell death pathways. Apoptosis 14:1289–1298PubMedCrossRefGoogle Scholar
  49. 49.
    Warren MW, Kobeissy FH, Liu MC, Hayes RL, Gold MS, Wang KK (2006) Ecstasy toxicity: a comparison to methamphetamine and traumatic brain injury. J Addict Dis 25:115–123PubMedCrossRefGoogle Scholar
  50. 50.
    Warren MW, Zheng W, Kobeissy FH, Cheng Liu M, Hayes RL, Gold MS, Larner SF, Wang KK (2007) Calpain- and caspase-mediated alphaII-spectrin and tau proteolysis in rat cerebrocortical neuronal cultures after ecstasy or methamphetamine exposure. Int J Neuropsychopharmacol 10:479–489PubMedCrossRefGoogle Scholar
  51. 51.
    Warren MW, Larner SF, Kobeissy FH, Brezing CA, Jeung JA, Hayes RL, Gold MS, Wang KK (2007) Calpain and caspase proteolytic markers co-localize with rat cortical neurons after exposure to methamphetamine and MDMA. Acta Neuropathol 114:277–286PubMedCrossRefGoogle Scholar
  52. 52.
    Warren MW, Kobeissy FH, Liu MC, Hayes RL, Gold MS, Wang KK (2005) Concurrent calpain and caspase-3 mediated proteolysis of alpha II-spectrin and tau in rat brain after methamphetamine exposure: a similar profile to traumatic brain injury. Life Sci 78:301–309PubMedCrossRefGoogle Scholar
  53. 53.
    Bromme D, Lecaille F (2009) Cathepsin K inhibitors for osteoporosis and potential off-target effects. Expert Opin Investig Drugs 18:585–600PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Drag M, Salvesen GS (2010) Emerging principles in protease-based drug discovery. Nat Rev Drug Discov 9:690–701PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Fonovic M, Turk B (2014) Cysteine cathepsins and their potential in clinical therapy and biomarker discovery. Proteomics Clin Appl 8:416–426PubMedCrossRefGoogle Scholar
  56. 56.
    Demeestere D, Dejonckheere E, Steeland S, Hulpiau P, Haustraete J, Devoogdt N, Wichert R, Becker-Pauly C, Van Wonterghem E, Dewaele S, Van Imschoot G, Aerts J, Arckens L, Saeys Y, Libert C, Vandenbroucke RE (2016) Development and validation of a small single-domain antibody that effectively inhibits matrix metalloproteinase 8. Mol Ther 24:890–902PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Ganguly K, Rejmak E, Mikosz M, Nikolaev E, Knapska E, Kaczmarek L (2013) Matrix metalloproteinase (MMP) 9 transcription in mouse brain induced by fear learning. J Biol Chem 288:20978–20991PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Wright JW, Meighan PC, Brown TE, Wiediger RV, Sorg BA, Harding JW (2009) Habituation-induced neural plasticity in the hippocampus and prefrontal cortex mediated by MMP-3. Behav Brain Res 203:27–34PubMedCrossRefGoogle Scholar
  59. 59.
    Brown TE, Wilson AR, Cocking DL, Sorg BA (2009) Inhibition of matrix metalloproteinase activity disrupts reconsolidation but not consolidation of a fear memory. Neurobiol Learn Mem 91:66–72PubMedCrossRefGoogle Scholar
  60. 60.
    Gingrich MB, Traynelis SF (2000) Serine proteases and brain damage—is there a link? Trends Neurosci 23:399–407PubMedCrossRefGoogle Scholar
  61. 61.
    Guroff G (1964) A neutral, calcium-activated proteinase from the soluble fraction of rat brain. J Biol Chem 239:149–155PubMedGoogle Scholar
  62. 62.
    Ishiura S, Murofushi H, Suzuki K, Imahori K (1978) Studies of a calcium-activated neutral protease from chicken skeletal muscle: I. Purification and characterization. J Biochem 84:225–230PubMedCrossRefGoogle Scholar
  63. 63.
    Croall DE, DeMartino GN (1991) Calcium-activated neutral protease (calpain) system: structure, function, and regulation. Physiol Rev 71:813–847PubMedGoogle Scholar
  64. 64.
    Diepenbroek M, Casadei N, Esmer H, Saido TC, Takano J, Kahle PJ, Nixon RA, Rao MV, Melki R, Pieri L, Helling S, Marcus K, Krueger R, Masliah E, Riess O, Nuber S (2014) Overexpression of the calpain-specific inhibitor calpastatin reduces human alpha-Synuclein processing, aggregation and synaptic impairment in [A30P]alphaSyn transgenic mice. Hum Mol Genet 23:3975–3989PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Rao MV, McBrayer MK, Campbell J, Kumar A, Hashim A, Sershen H, Stavrides PH, Ohno M, Hutton M, Nixon RA (2014) Specific calpain inhibition by calpastatin prevents tauopathy and neurodegeneration and restores normal lifespan in tau P301L mice. J Neurosci 34:9222–9234PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Vosler PS, Brennan CS, Chen J (2008) Calpain-mediated signaling mechanisms in neuronal injury and neurodegeneration. Mol Neurobiol 38:78–100PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Cong J, Goll DE, Peterson AM, Kapprell HP (1989) The role of autolysis in activity of the Ca2+-dependent proteinases (mu-calpain and m-calpain). J Biol Chem 264:10096–10103PubMedGoogle Scholar
  68. 68.
    Ohno S, Minoshima S, Kudoh J, Fukuyama R, Shimizu Y, Ohmi-Imajoh S, Shimizu N, Suzuki K (1990) Four genes for the calpain family locate on four distinct human chromosomes. Cytogenet Cell Genet 53:225–229PubMedCrossRefGoogle Scholar
  69. 69.
    Mitsios N, Gaffney J, Kumar P, Krupinski J, Kumar S, Slevin M (2006) Pathophysiology of acute ischaemic stroke: an analysis of common signalling mechanisms and identification of new molecular targets. Pathobiology 73:159–175PubMedCrossRefGoogle Scholar
  70. 70.
    MacDonald JF, Xiong ZG, Jackson MF (2006) Paradox of Ca2+ signaling, cell death and stroke. Trends Neurosci 29:75–81PubMedCrossRefGoogle Scholar
  71. 71.
    Urazaev AK, Magsumov ST, Poletayev GI, Nikolsky EE, Vyskocil F (1995) Muscle NMDA receptors regulate the resting membrane potential through NO-synthase. Physiol Res 44:205–208PubMedGoogle Scholar
  72. 72.
    Berridge MJ (1993) Inositol trisphosphate and calcium signalling. Nature 361:315–325PubMedCrossRefGoogle Scholar
  73. 73.
    Nakashima Y, Nishimura S, Maeda A, Barsoumian EL, Hakamata Y, Nakai J, Allen PD, Imoto K, Kita T (1997) Molecular cloning and characterization of a human brain ryanodine receptor. FEBS Lett 417:157–162PubMedCrossRefGoogle Scholar
  74. 74.
    Shcherbatko A, Ono F, Mandel G, Brehm P (1999) Voltage-dependent sodium channel function is regulated through membrane mechanics. Biophys J 77:1945–1959PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Wolf JA, Stys PK, Lusardi T, Meaney D, Smith DH (2001) Traumatic axonal injury induces calcium influx modulated by tetrodotoxin-sensitive sodium channels. J Neurosci 21:1923–1930PubMedGoogle Scholar
  76. 76.
    Casado M, Ascher P (1998) Opposite modulation of NMDA receptors by lysophospholipids and arachidonic acid: common features with mechanosensitivity. J Physiol 513(Pt 2):317–330PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Brittain MK, Brustovetsky T, Sheets PL, Brittain JM, Khanna R, Cummins TR, Brustovetsky N (2012) Delayed calcium dysregulation in neurons requires both the NMDA receptor and the reverse Na+/Ca2+ exchanger. Neurobiol Dis 46:109–117PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Zhou M, Xu W, Liao G, Bi X, Baudry M (2009) Neuroprotection against neonatal hypoxia/ischemia-induced cerebral cell death by prevention of calpain-mediated mGluR1alpha truncation. Exp Neurol 218:75–82PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Ahmed SM, Weber JT, Liang S, Willoughby KA, Sitterding HA, Rzigalinski BA, Ellis EF (2002) NMDA receptor activation contributes to a portion of the decreased mitochondrial membrane potential and elevated intracellular free calcium in strain-injured neurons. J Neurotrauma 19:1619–1629PubMedCrossRefGoogle Scholar
  80. 80.
    Dhillon HS, Carman HM, Prasad RM (1999) Regional activities of phospholipase C after experimental brain injury in the rat. Neurochem Res 24:751–755PubMedCrossRefGoogle Scholar
  81. 81.
    Weber JT (2012) Altered calcium signaling following traumatic brain injury. Front Pharmacol 3:60PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Launay S, Hermine O, Fontenay M, Kroemer G, Solary E, Garrido C (2005) Vital functions for lethal caspases. Oncogene 24:5137–5148PubMedCrossRefGoogle Scholar
  83. 83.
    Toescu EC (1998) Apoptosis and cell death in neuronal cells: where does Ca2+ fit in? Cell Calcium 24:387–403PubMedCrossRefGoogle Scholar
  84. 84.
    Krajewska M, Kim H, Shin E, Kennedy S, Duffy MJ, Wong YF, Marr D, Mikolajczyk J, Shabaik A, Meinhold-Heerlein I, Huang X, Banares S, Hedayat H, Reed JC, Krajewski S (2005) Tumor-associated alterations in caspase-14 expression in epithelial malignancies. Clin Cancer Res 11:5462–5471PubMedCrossRefGoogle Scholar
  85. 85.
    Jian Z, Ding S, Deng H, Wang J, Yi W, Wang L, Zhu S, Gu L, Xiong X (2016) Probenecid protects against oxygen-glucose deprivation injury in primary astrocytes by regulating inflammasome activity. Brain Res 1643:123–129PubMedCrossRefGoogle Scholar
  86. 86.
    de Rivero Vaccari JP, Brand F 3rd, Adamczak S, Lee SW, Perez-Barcena J, Wang MY, Bullock MR, Dietrich WD, Keane RW (2016) Exosome-mediated inflammasome signaling after central nervous system injury. J Neurochem 136(Suppl 1):39–48PubMedCrossRefGoogle Scholar
  87. 87.
    Wang YC, Li WZ, Wu Y, Yin YY, Dong LY, Chen ZW, Wu WN (2015) Acid-sensing ion channel 1a contributes to the effect of extracellular acidosis on NLRP1 inflammasome activation in cortical neurons. J Neuroinflammation 12:246PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Fann DY, Lee SY, Manzanero S, Tang SC, Gelderblom M, Chunduri P, Bernreuther C, Glatzel M, Cheng YL, Thundyil J, Widiapradja A, Lok KZ, Foo SL, Wang YC, Li YI, Drummond GR, Basta M, Magnus T, Jo DG, Mattson MP, Sobey CG, Arumugam TV (2013) Intravenous immunoglobulin suppresses NLRP1 and NLRP3 inflammasome-mediated neuronal death in ischemic stroke. Cell Death Dis 4:e790PubMedCrossRefGoogle Scholar
  89. 89.
    Fan TJ, Han LH, Cong RS, Liang J (2005) Caspase family proteases and apoptosis. Acta Biochim Biophys Sin 37:719–727PubMedCrossRefGoogle Scholar
  90. 90.
    Kuwana T, Mackey MR, Perkins G, Ellisman MH, Latterich M, Schneiter R, Green DR, Newmeyer DD (2002) Bid, Bax, and lipids cooperate to form supramolecular openings in the outer mitochondrial membrane. Cell 111:331–342PubMedCrossRefGoogle Scholar
  91. 91.
    Martinon F, Tschopp J (2004) Inflammatory caspases: linking an intracellular innate immune system to autoinflammatory diseases. Cell 117:561–574PubMedCrossRefGoogle Scholar
  92. 92.
    Blomgren K, Zhu C, Wang X, Karlsson JO, Leverin AL, Bahr BA, Mallard C, Hagberg H (2001) Synergistic activation of caspase-3 by m-calpain after neonatal hypoxia-ischemia: a mechanism of "pathological apoptosis"? J Biol Chem 276:10191–10198PubMedCrossRefGoogle Scholar
  93. 93.
    Mandic A, Hansson J, Linder S, Shoshan MC (2003) Cisplatin induces endoplasmic reticulum stress and nucleus-independent apoptotic signaling. J Biol Chem 278:9100–9106PubMedCrossRefGoogle Scholar
  94. 94.
    Turk V, Turk B, Guncar G, Turk D, Kos J (2002) Lysosomal cathepsins: structure, role in antigen processing and presentation, and cancer. Adv Enzyme Regul 42:285–303PubMedCrossRefGoogle Scholar
  95. 95.
    Vasiljeva O, Reinheckel T, Peters C, Turk D, Turk V, Turk B (2007) Emerging roles of cysteine cathepsins in disease and their potential as drug targets. Curr Pharm Des 13:387–403PubMedCrossRefGoogle Scholar
  96. 96.
    Tanaka M, Yamada H, Nishikawa S, Mori H, Ochi Y, Horai N, Li M, Amizuka N (2016) Joint degradation in a monkey model of collagen-induced arthritis: role of cathepsin K based on biochemical markers and histological evaluation. Int J Rheumatol 2016:8938916PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Stoeckle C, Gouttefangeas C, Hammer M, Weber E, Melms A, Tolosa E (2009) Cathepsin W expressed exclusively in CD8+ T cells and NK cells, is secreted during target cell killing but is not essential for cytotoxicity in human CTLs. Exp Hematol 37:266–275PubMedCrossRefGoogle Scholar
  98. 98.
    McMahon PJ, Panczykowski DM, Yue JK, Puccio AM, Inoue T, Sorani MD, Lingsma HF, Maas AI, Valadka AB, Yuh EL, Mukherjee P, Manley GT, Okonkwo DO, Investigators T-T (2015) Measurement of the glial fibrillary acidic protein and its breakdown products GFAP-BDP biomarker for the detection of traumatic brain injury compared to computed tomography and magnetic resonance imaging. J Neurotrauma 32:527–533PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Droga-Mazovec G, Bojic L, Petelin A, Ivanova S, Romih R, Repnik U, Salvesen GS, Stoka V, Turk V, Turk B (2008) Cysteine cathepsins trigger caspase-dependent cell death through cleavage of bid and antiapoptotic Bcl-2 homologues. J Biol Chem 283:19140–19150PubMedCrossRefGoogle Scholar
  100. 100.
    Centers for Disease Control and Prevention (2013) CDC grand rounds: reducing severe traumatic brain injury in the United States. MMWR Morb Mortal Wkly Rep 62:549–552Google Scholar
  101. 101.
    Langlois JA, Rutland-Brown W, Wald MM (2006) The epidemiology and impact of traumatic brain injury: a brief overview. J Head Trauma Rehabil 21:375–378PubMedCrossRefGoogle Scholar
  102. 102.
    Gean AD, Fischbein NJ (2010) Head trauma. Neuroimaging Clin N Am 20:527–556PubMedCrossRefGoogle Scholar
  103. 103.
    Rusnak M (2013) Traumatic brain injury: giving voice to a silent epidemic. Nat Rev Neurol 9:186–187PubMedCrossRefGoogle Scholar
  104. 104.
    Vaishnavi S, Rao V, Fann JR (2009) Neuropsychiatric problems after traumatic brain injury: unraveling the silent epidemic. Psychosomatics 50:198–205PubMedCrossRefGoogle Scholar
  105. 105.
    Laskowski RA, Creed JA, Raghupathi R (2015) Pathophysiology of mild TBI: implications for altered signaling pathways. In: Kobeissy FH (ed) Brain neurotrauma: molecular, neuropsychological, and rehabilitation aspects. CRC Press/Taylor & Francis, Boca Raton, FL, pp 35–42Google Scholar
  106. 106.
    Ziebell JM, Morganti-Kossmann MC (2010) Involvement of pro- and anti-inflammatory cytokines and chemokines in the pathophysiology of traumatic brain injury. Neurotherapeutics 7:22–30PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Semple BD, Bye N, Rancan M, Ziebell JM, Morganti-Kossmann MC (2010) Role of CCL2 (MCP-1) in traumatic brain injury (TBI): evidence from severe TBI patients and CCL2−/− mice. J Cereb Blood Flow Metab 30:769–782PubMedCrossRefGoogle Scholar
  108. 108.
    Woodcock T, Morganti-Kossmann MC (2013) The role of markers of inflammation in traumatic brain injury. Front Neurol 4:18PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Di Battista AP, Rhind SG, Hutchison MG, Hassan S, Shiu MY, Inaba K, Topolovec-Vranic J, Neto AC, Rizoli SB, Baker AJ (2016) Inflammatory cytokine and chemokine profiles are associated with patient outcome and the hyperadrenergic state following acute brain injury. J Neuroinflammation 13:40PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Mayeux JP, Katz PS, Edwards S, Middleton J, Molina P (2016) Inhibition of endocannabinoid degradation improves outcomes from mild traumatic brain injury: a mechanistic role for synaptic hyperexcitability. J Neurotrauma 34(2):436–443PubMedCrossRefGoogle Scholar
  111. 111.
    Kobeissy FH, Ottens AK, Zhang Z, Liu MC, Denslow ND, Dave JR, Tortella FC, Hayes RL, Wang KK (2006) Novel differential neuroproteomics analysis of traumatic brain injury in rats. Mol Cell Proteomics 5:1887–1898PubMedCrossRefGoogle Scholar
  112. 112.
    Witkowski C, Harkins J (2009) Using the GELFREE 8100 Fractionation System for molecular weight-based fractionation with liquid phase recovery. J Vis Exp (39):1842Google Scholar
  113. 113.
    Abou-Abbass H, Bahmad H, Abou-El-Hassan H, Zhu R, Zhou S, Dong X, Hamade E, Mallah K, Zebian A, Ramadan N, Mondello S, Fares J, Comair Y, Atweh S, Darwish H, Zibara K, Mechref Y, Kobeissy F (2016) Deciphering glycomics and neuroproteomic alterations in experimental traumatic brain injury: Comparative analysis of aspirin and clopidogrel treatment. Electrophoresis 37:1562–1576PubMedCrossRefGoogle Scholar
  114. 114.
    Hui H, Rao W, Zhang L, Xie Z, Peng C, Su N, Wang K, Wang L, Luo P, Hao YL, Zhang S, Fei Z (2016) Inhibition of Na(+)-K(+)-2Cl(−) Cotransporter-1 attenuates traumatic brain injury-induced neuronal apoptosis via regulation of Erk signaling. Neurochem Int 94:23–31PubMedCrossRefGoogle Scholar
  115. 115.
    Stoica BA, Faden AI (2010) Cell death mechanisms and modulation in traumatic brain injury. Neurotherapeutics 7:3–12PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Saatman KE, Creed J, Raghupathi R (2010) Calpain as a therapeutic target in traumatic brain injury. Neurotherapeutics 7:31–42PubMedPubMedCentralCrossRefGoogle Scholar
  117. 117.
    Yamada KH, Kozlowski DA, Seidl SE, Lance S, Wieschhaus AJ, Sundivakkam P, Tiruppathi C, Chishti I, Herman IM, Kuchay SM, Chishti AH (2012) Targeted gene inactivation of calpain-1 suppresses cortical degeneration due to traumatic brain injury and neuronal apoptosis induced by oxidative stress. J Biol Chem 287:13182–13193PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Kobeissy FH, Liu MC, Yang Z, Zhang Z, Zheng W, Glushakova O, Mondello S, Anagli J, Hayes RL, Wang KK (2015) Degradation of betaII-spectrin protein by calpain-2 and caspase-3 under neurotoxic and traumatic brain injury conditions. Mol Neurobiol 52:696–709PubMedCrossRefGoogle Scholar
  119. 119.
    Kobeissy FH et al (2006) Novel differential neuroproteomics analysis of traumatic brain injury in rats. Mol Cell Proteomics 5(10):1887–1898PubMedCrossRefGoogle Scholar
  120. 120.
    Schober ME et al (2014) Alpha II Spectrin breakdown products in immature Sprague Dawley rat hippocampus and cortex after traumatic brain injury. Brain Res 1574:105–112PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Pike BR et al (2001) Accumulation of non-erythroid alpha II-spectrin and calpain-cleaved alpha II-spectrin breakdown products in cerebrospinal fluid after traumatic brain injury in rats. J Neurochem 78(6):1297–1306PubMedCrossRefGoogle Scholar
  122. 122.
    Aikman J et al (2006) Alpha-II-spectrin after controlled cortical impact in the immature rat brain. Dev Neurosci 28(4–5):457–465PubMedCrossRefGoogle Scholar
  123. 123.
    McGinn MJ et al (2009) Biochemical, structural, and biomarker evidence for calpain-mediated cytoskeletal change after diffuse brain injury uncomplicated by contusion. J Neuropathol Exp Neurol 68(3):241–249PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Valiyaveettil M et al (2014) Cytoskeletal protein alpha-II spectrin degradation in the brain of repeated blast exposed mice. Brain Res 1549:32–41PubMedCrossRefGoogle Scholar
  125. 125.
    Chen S et al (2016) Role of alpha-II-spectrin breakdown products in the prediction of the severity and clinical outcome of acute traumatic brain injury. Exp Ther Med 11(5):2049–2053PubMedPubMedCentralGoogle Scholar
  126. 126.
    Farkas O et al (2005) Spectrin breakdown products in the cerebrospinal fluid in severe head injury—preliminary observations. Acta Neurochir 147(8):855–861PubMedCrossRefGoogle Scholar
  127. 127.
    Cardali S, Maugeri R (2006) Detection of alphaII-spectrin and breakdown products in humans after severe traumatic brain injury. J Neurosurg Sci 50(2):25–31PubMedGoogle Scholar
  128. 128.
    Conti A et al (2004) Proteome study of human cerebrospinal fluid following traumatic brain injury indicates fibrin(ogen) degradation products as trauma-associated markers. J Neurotrauma 21(7):854–863PubMedCrossRefGoogle Scholar
  129. 129.
    Pineda JA et al (2007) Clinical significance of alphaII-spectrin breakdown products in cerebrospinal fluid after severe traumatic brain injury. J Neurotrauma 24(2):354–366PubMedCrossRefGoogle Scholar
  130. 130.
    Brophy GM et al (2009) alphaII-Spectrin breakdown product cerebrospinal fluid exposure metrics suggest differences in cellular injury mechanisms after severe traumatic brain injury. J Neurotrauma 26(4):471–479PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Mondello S et al (2010) alphaII-spectrin breakdown products (SBDPs): diagnosis and outcome in severe traumatic brain injury patients. J Neurotrauma 27(7):1203–1213PubMedPubMedCentralCrossRefGoogle Scholar
  132. 132.
    Berger RP et al (2012) Serum concentrations of ubiquitin C-terminal hydrolase-L1 and alphaII-spectrin breakdown product 145 kDa correlate with outcome after pediatric TBI. J Neurotrauma 29(1):162–167PubMedPubMedCentralCrossRefGoogle Scholar
  133. 133.
    Kobeissy FH et al (2015) Degradation of betaII-spectrin protein by calpain-2 and caspase-3 under neurotoxic and traumatic brain injury conditions. Mol Neurobiol 52(1):696–709PubMedCrossRefGoogle Scholar
  134. 134.
    Liu MC et al (2006) Comparing calpain- and caspase-3-mediated degradation patterns in traumatic brain injury by differential proteome analysis. Biochem J 394(Pt 3):715–725PubMedPubMedCentralCrossRefGoogle Scholar
  135. 135.
    Reeves TM et al (2010) Proteolysis of submembrane cytoskeletal proteins ankyrin-G and alphaII-spectrin following diffuse brain injury: a role in white matter vulnerability at Nodes of Ranvier. Brain Pathol 20(6):1055–1068PubMedPubMedCentralCrossRefGoogle Scholar
  136. 136.
    Liu MC et al (2011) Dual vulnerability of tau to calpains and caspase-3 proteolysis under neurotoxic and neurodegenerative conditions. ASN Neuro 3(1):e00051PubMedGoogle Scholar
  137. 137.
    Cartagena CM et al (2016) Subacute changes in cleavage processing of amyloid precursor protein and tau following penetrating traumatic brain injury. PLoS One 11(7):e0158576PubMedPubMedCentralCrossRefGoogle Scholar
  138. 138.
    Lee YB et al (2000) Rapid increase in immunoreactivity to GFAP in astrocytes in vitro induced by acidic pH is mediated by calcium influx and calpain I. Brain Res 864(2):220–229PubMedCrossRefGoogle Scholar
  139. 139.
    Zhang Z et al (2014) Human traumatic brain injury induces autoantibody response against glial fibrillary acidic protein and its breakdown products. PLoS One 9(3):e92698PubMedPubMedCentralCrossRefGoogle Scholar
  140. 140.
    Bermpohl D et al (2006) Traumatic brain injury in mice deficient in Bid: effects on histopathology and functional outcome. J Cereb Blood Flow Metab 26(5):625–633PubMedCrossRefGoogle Scholar
  141. 141.
    Xiong Y et al (2001) Appearance of shortened Bcl-2 and Bax proteins and lack of evidence for apoptosis in rat forebrain after severe experimental traumatic brain injury. Biochem Biophys Res Commun 286(2):401–405PubMedCrossRefGoogle Scholar
  142. 142.
    Lau A et al (2006) Inhibition of caspase-mediated apoptosis by peroxynitrite in traumatic brain injury. J Neurosci 26(45):11540–11553PubMedCrossRefGoogle Scholar
  143. 143.
    Yang Z et al (2014) Dual vulnerability of TDP-43 to calpain and caspase-3 proteolysis after neurotoxic conditions and traumatic brain injury. J Cereb Blood Flow Metab 34(9):1444–1452PubMedPubMedCentralCrossRefGoogle Scholar
  144. 144.
    Thompson SN et al (2006) Relationship of calpain-mediated proteolysis to the expression of axonal and synaptic plasticity markers following traumatic brain injury in mice. Exp Neurol 201(1):253–265PubMedCrossRefGoogle Scholar
  145. 145.
    Ottens AK et al (2008) Proteolysis of multiple myelin basic protein isoforms after neurotrauma: characterization by mass spectrometry. J Neurochem 104(5):1404–1414PubMedCrossRefGoogle Scholar
  146. 146.
    Liu MC et al (2006) Extensive degradation of myelin basic protein isoforms by calpain following traumatic brain injury. J Neurochem 98(3):700–712PubMedCrossRefGoogle Scholar
  147. 147.
    Zhang C et al (1999) Regional and temporal alterations in DNA fragmentation factor (DFF)-like proteins following experimental brain trauma in the rat. J Neurochem 73(4):1650–1659PubMedCrossRefGoogle Scholar
  148. 148.
    Robinson S et al (2016) Imaging and serum biomarkers reflecting the functional efficacy of extended erythropoietin treatment in rats following infantile traumatic brain injury. J Neurosurg Pediatr 17(6):739–755PubMedPubMedCentralCrossRefGoogle Scholar
  149. 149.
    Puskarjov M et al (2012) Activity-dependent cleavage of the K-Cl cotransporter KCC2 mediated by calcium-activated protease calpain. J Neurosci 32(33):11356–11364PubMedCrossRefGoogle Scholar
  150. 150.
    Hadass O et al (2013) Selective inhibition of matrix metalloproteinase-9 attenuates secondary damage resulting from severe traumatic brain injury. PLoS One 8(10):e76904PubMedPubMedCentralCrossRefGoogle Scholar
  151. 151.
    Bajor M et al (2012) Synaptic cell adhesion molecule-2 and collapsin response mediator protein-2 are novel members of the matrix metalloproteinase-9 degradome. J Neurochem 122(4):775–788PubMedCrossRefGoogle Scholar
  152. 152.
    Zhang Z et al (2007) Calpain-mediated collapsin response mediator protein-1, -2, and -4 proteolysis after neurotoxic and traumatic brain injury. J Neurotrauma 24(3):460–472PubMedCrossRefGoogle Scholar
  153. 153.
    Warren KM, Reeves TM, Phillips LL (2012) MT5-MMP, ADAM-10, and N-cadherin act in concert to facilitate synapse reorganization after traumatic brain injury. J Neurotrauma 29(10):1922–1940PubMedPubMedCentralCrossRefGoogle Scholar
  154. 154.
    Smani T, Dionisio N, Lopez JJ, Berna-Erro A, Rosado JA (2014) Cytoskeletal and scaffolding proteins as structural and functional determinants of TRP channels. Biochim Biophys Acta 1838:658–664PubMedCrossRefGoogle Scholar
  155. 155.
    Dominguez R, Holmes KC (2011) Actin structure and function. Annu Rev Biophys 40:169–186PubMedPubMedCentralCrossRefGoogle Scholar
  156. 156.
    Reeves TM, Greer JE, Vanderveer AS, Phillips LL (2010) Proteolysis of submembrane cytoskeletal proteins ankyrin-G and alphaII-spectrin following diffuse brain injury: a role in white matter vulnerability at Nodes of Ranvier. Brain Pathol 20:1055–1068PubMedPubMedCentralCrossRefGoogle Scholar
  157. 157.
    Kevenaar JT, Hoogenraad CC (2015) The axonal cytoskeleton: from organization to function. Front Mol Neurosci 8:44PubMedPubMedCentralCrossRefGoogle Scholar
  158. 158.
    He J, Zhou R, Wu Z, Carrasco MA, Kurshan PT, Farley JE, Simon DJ, Wang G, Han B, Hao J, Heller E, Freeman MR, Shen K, Maniatis T, Tessier-Lavigne M, Zhuang X (2016) Prevalent presence of periodic actin-spectrin-based membrane skeleton in a broad range of neuronal cell types and animal species. Proc Natl Acad Sci U S A 113:6029–6034PubMedPubMedCentralCrossRefGoogle Scholar
  159. 159.
    Cheng G, Kong RH, Zhang LM, Zhang JN (2012) Mitochondria in traumatic brain injury and mitochondrial-targeted multipotential therapeutic strategies. Br J Pharmacol 167:699–719PubMedPubMedCentralCrossRefGoogle Scholar
  160. 160.
    Uchino H, Ogihara Y, Fukui H, Chijiiwa M, Sekine S, Hara N, Elmer E (2016) Brain injury following cardiac arrest: pathophysiology for neurocritical care. J Intensive Care 4:31PubMedPubMedCentralCrossRefGoogle Scholar
  161. 161.
    Lin SC, Gou GH, Hsia CW, Ho CW, Huang KL, Wu YF, Lee SY, Chen YH (2016) Simulated microgravity disrupts cytoskeleton organization and increases apoptosis of rat neural crest stem cells via upregulating CXCR4 expression and RhoA-ROCK1-p38 MAPK-p53 signaling. Stem Cells Dev 25(15):1172–1193PubMedCrossRefGoogle Scholar
  162. 162.
    Aktug H, Acikgoz E, Uysal A, Oltulu F, Oktem G, Yigitturk G, Demir K, Yavasoglu A, Bozok Cetintas V (2016) Comparison of cell cycle components, apoptosis and cytoskeleton-related molecules and therapeutic effects of flavopiridol and geldanamycin on the mouse fibroblast, lung cancer and embryonic stem cells. Tumour Biol 37(9):12423–12440PubMedCrossRefGoogle Scholar
  163. 163.
    Desouza M, Gunning PW, Stehn JR (2012) The actin cytoskeleton as a sensor and mediator of apoptosis. Bioarchitecture 2:75–87PubMedPubMedCentralCrossRefGoogle Scholar
  164. 164.
    Gourlay CW, Ayscough KR (2005) The actin cytoskeleton: a key regulator of apoptosis and ageing? Nat Rev Mol Cell Biol 6:583–589PubMedCrossRefGoogle Scholar
  165. 165.
    Liu MC, Akle V, Zheng W, Dave JR, Tortella FC, Hayes RL, Wang KK (2006) Comparing calpain- and caspase-3-mediated degradation patterns in traumatic brain injury by differential proteome analysis. Biochem J 394:715–725PubMedPubMedCentralCrossRefGoogle Scholar
  166. 166.
    Schober ME, Requena DF, Davis LJ, Metzger RR, Bennett KS, Morita D, Niedzwecki C, Yang Z, Wang KK (2014) Alpha II Spectrin breakdown products in immature Sprague Dawley rat hippocampus and cortex after traumatic brain injury. Brain Res 1574:105–112PubMedPubMedCentralCrossRefGoogle Scholar
  167. 167.
    McGinn MJ, Kelley BJ, Akinyi L, Oli MW, Liu MC, Hayes RL, Wang KK, Povlishock JT (2009) Biochemical, structural, and biomarker evidence for calpain-mediated cytoskeletal change after diffuse brain injury uncomplicated by contusion. J Neuropathol Exp Neurol 68:241–249PubMedPubMedCentralCrossRefGoogle Scholar
  168. 168.
    Pike BR, Flint J, Dutta S, Johnson E, Wang KK, Hayes RL (2001) Accumulation of non-erythroid alpha II-spectrin and calpain-cleaved alpha II-spectrin breakdown products in cerebrospinal fluid after traumatic brain injury in rats. J Neurochem 78:1297–1306PubMedCrossRefGoogle Scholar
  169. 169.
    Aikman J, O'Steen B, Silver X, Torres R, Boslaugh S, Blackband S, Padgett K, Wang KK, Hayes R, Pineda J (2006) Alpha-II-spectrin after controlled cortical impact in the immature rat brain. Dev Neurosci 28:457–465PubMedCrossRefGoogle Scholar
  170. 170.
    Chen S, Shi Q, Zheng S, Luo L, Yuan S, Wang X, Cheng Z, Zhang W (2016) Role of alpha-II-spectrin breakdown products in the prediction of the severity and clinical outcome of acute traumatic brain injury. Exp Ther Med 11:2049–2053PubMedPubMedCentralGoogle Scholar
  171. 171.
    Farkas O, Polgar B, Szekeres-Bartho J, Doczi T, Povlishock JT, Buki A (2005) Spectrin breakdown products in the cerebrospinal fluid in severe head injury—preliminary observations. Acta Neurochir 147:855–861PubMedCrossRefGoogle Scholar
  172. 172.
    Cardali S, Maugeri R (2006) Detection of alphaII-spectrin and breakdown products in humans after severe traumatic brain injury. J Neurosurg Sci 50:25–31PubMedGoogle Scholar
  173. 173.
    Conti A, Sanchez-Ruiz Y, Bachi A, Beretta L, Grandi E, Beltramo M, Alessio M (2004) Proteome study of human cerebrospinal fluid following traumatic brain injury indicates fibrin(ogen) degradation products as trauma-associated markers. J Neurotrauma 21:854–863PubMedCrossRefGoogle Scholar
  174. 174.
    Pineda JA, Lewis SB, Valadka AB, Papa L, Hannay HJ, Heaton SC, Demery JA, Liu MC, Aikman JM, Akle V, Brophy GM, Tepas JJ, Wang KK, Robertson CS, Hayes RL (2007) Clinical significance of alphaII-spectrin breakdown products in cerebrospinal fluid after severe traumatic brain injury. J Neurotrauma 24:354–366PubMedCrossRefGoogle Scholar
  175. 175.
    Brophy GM, Pineda JA, Papa L, Lewis SB, Valadka AB, Hannay HJ, Heaton SC, Demery JA, Liu MC, Tepas JJ 3rd, Gabrielli A, Robicsek S, Wang KK, Robertson CS, Hayes RL (2009) alphaII-Spectrin breakdown product cerebrospinal fluid exposure metrics suggest differences in cellular injury mechanisms after severe traumatic brain injury. J Neurotrauma 26:471–479PubMedPubMedCentralCrossRefGoogle Scholar
  176. 176.
    Mondello S, Robicsek SA, Gabrielli A, Brophy GM, Papa L, Tepas J, Robertson C, Buki A, Scharf D, Jixiang M, Akinyi L, Muller U, Wang KK, Hayes RL (2010) alphaII-spectrin breakdown products (SBDPs): diagnosis and outcome in severe traumatic brain injury patients. J Neurotrauma 27:1203–1213PubMedPubMedCentralCrossRefGoogle Scholar
  177. 177.
    Berger RP, Hayes RL, Richichi R, Beers SR, Wang KK (2012) Serum concentrations of ubiquitin C-terminal hydrolase-L1 and alphaII-spectrin breakdown product 145 kDa correlate with outcome after pediatric TBI. J Neurotrauma 29:162–167PubMedPubMedCentralCrossRefGoogle Scholar
  178. 178.
    Bennett V, Lorenzo DN (2013) Spectrin- and ankyrin-based membrane domains and the evolution of vertebrates. Curr Top Membr 72:1–37PubMedCrossRefGoogle Scholar
  179. 179.
    Du X, West MB, Cheng W, Ewert DL, Li W, Saunders D, Towner RA, Floyd RA, Kopke RD (2016) Ameliorative effects of antioxidants on the hippocampal accumulation of pathologic tau in a rat model of blast-induced traumatic brain injury. Oxid Med Cell Longev 2016:4159357PubMedCrossRefGoogle Scholar
  180. 180.
    Smith DH, Johnson VE, Stewart W (2013) Chronic neuropathologies of single and repetitive TBI: substrates of dementia? Nat Rev Neurol 9:211–221PubMedPubMedCentralCrossRefGoogle Scholar
  181. 181.
    Lau DH, Hogseth M, Phillips EC, O'Neill MJ, Pooler AM, Noble W, Hanger DP (2016) Critical residues involved in tau binding to fyn: implications for tau phosphorylation in Alzheimer’s disease. Acta Neuropathol Commun 4:49PubMedPubMedCentralCrossRefGoogle Scholar
  182. 182.
    Siman R, McIntosh TK, Soltesz KM, Chen Z, Neumar RW, Roberts VL (2004) Proteins released from degenerating neurons are surrogate markers for acute brain damage. Neurobiol Dis 16:311–320PubMedCrossRefGoogle Scholar
  183. 183.
    Marklund N, Blennow K, Zetterberg H, Ronne-Engstrom E, Enblad P, Hillered L (2009) Monitoring of brain interstitial total tau and beta amyloid proteins by microdialysis in patients with traumatic brain injury. J Neurosurg 110:1227–1237PubMedCrossRefGoogle Scholar
  184. 184.
    Lucke-Wold BP, Smith KE, Nguyen L, Turner RC, Logsdon AF, Jackson GJ, Huber JD, Rosen CL, Miller DB (2015) Sleep disruption and the sequelae associated with traumatic brain injury. Neurosci Biobehav Rev 55:68–77PubMedPubMedCentralCrossRefGoogle Scholar
  185. 185.
    Liu MC, Kobeissy F, Zheng W, Zhang Z, Hayes RL, Wang KK (2011) Dual vulnerability of tau to calpains and caspase-3 proteolysis under neurotoxic and neurodegenerative conditions. ASN Neuro 3:e00051PubMedGoogle Scholar
  186. 186.
    Cartagena CM, Mountney A, Hwang H, Swiercz A, Rammelkamp Z, Boutte AM, Shear DA, Tortella FC, Schmid KE (2016) Subacute changes in cleavage processing of amyloid precursor protein and tau following penetrating traumatic brain injury. PLoS One 11:e0158576PubMedPubMedCentralCrossRefGoogle Scholar
  187. 187.
    Amadoro G, Corsetti V, Florenzano F, Atlante A, Ciotti MT, Mongiardi MP, Bussani R, Nicolin V, Nori SL, Campanella M, Calissano P (2014) AD-linked, toxic NH2 human tau affects the quality control of mitochondria in neurons. Neurobiol Dis 62:489–507PubMedCrossRefGoogle Scholar
  188. 188.
    Amadoro G, Corsetti V, Sancesario GM, Lubrano A, Melchiorri G, Bernardini S, Calissano P, Sancesario G (2014) Cerebrospinal fluid levels of a 20–22 kDa NH2 fragment of human tau provide a novel neuronal injury biomarker in Alzheimer’s disease and other dementias. J Alzheimers Dis 42:211–226PubMedGoogle Scholar
  189. 189.
    Sofroniew MV, Vinters HV (2010) Astrocytes: biology and pathology. Acta Neuropathol 119:7–35PubMedCrossRefGoogle Scholar
  190. 190.
    Lee YB, Du S, Rhim H, Lee EB, Markelonis GJ, Oh TH (2000) Rapid increase in immunoreactivity to GFAP in astrocytes in vitro induced by acidic pH is mediated by calcium influx and calpain I. Brain Res 864:220–229PubMedCrossRefGoogle Scholar
  191. 191.
    Okonkwo DO, Yue JK, Puccio AM, Panczykowski DM, Inoue T, McMahon PJ, Sorani MD, Yuh EL, Lingsma HF, Maas AI, Valadka AB, Manley GT, Transforming R, Clinical Knowledge in Traumatic Brain Injury, I (2013) GFAP-BDP as an acute diagnostic marker in traumatic brain injury: results from the prospective transforming research and clinical knowledge in traumatic brain injury study. J Neurotrauma 30:1490–1497PubMedPubMedCentralCrossRefGoogle Scholar
  192. 192.
    Papa L, Lewis LM, Falk JL, Zhang Z, Silvestri S, Giordano P, Brophy GM, Demery JA, Dixit NK, Ferguson I, Liu MC, Mo J, Akinyi L, Schmid K, Mondello S, Robertson CS, Tortella FC, Hayes RL, Wang KK (2012) Elevated levels of serum glial fibrillary acidic protein breakdown products in mild and moderate traumatic brain injury are associated with intracranial lesions and neurosurgical intervention. Ann Emerg Med 59:471–483PubMedCrossRefGoogle Scholar
  193. 193.
    Mondello S, Papa L, Buki A, Bullock MR, Czeiter E, Tortella FC, Wang KK, Hayes RL (2011) Neuronal and glial markers are differently associated with computed tomography findings and outcome in patients with severe traumatic brain injury: a case control study. Crit Care 15:R156PubMedPubMedCentralCrossRefGoogle Scholar
  194. 194.
    Papa L, Zonfrillo MR, Ramirez J, Silvestri S, Giordano P, Braga CF, Tan CN, Ameli NJ, Lopez M, Mittal MK (2015) Performance of glial fibrillary acidic protein in detecting traumatic intracranial lesions on computed tomography in children and youth with mild head trauma. Acad Emerg Med 22:1274–1282PubMedPubMedCentralCrossRefGoogle Scholar
  195. 195.
    Takala RS, Posti JP, Runtti H, Newcombe VF, Outtrim J, Katila AJ, Frantzen J, Ala-Seppala H, Kyllonen A, Maanpaa HR, Tallus J, Hossain MI, Coles JP, Hutchinson P, van Gils M, Menon DK, Tenovuo O (2016) Glial fibrillary acidic protein and ubiquitin C-terminal hydrolase-L1 as outcome predictors in traumatic brain injury. World Neurosurg 87:8–20PubMedCrossRefGoogle Scholar
  196. 196.
    Mondello S, Jeromin A, Buki A, Bullock R, Czeiter E, Kovacs N, Barzo P, Schmid K, Tortella F, Wang KK, Hayes RL (2012) Glial neuronal ratio: a novel index for differentiating injury type in patients with severe traumatic brain injury. J Neurotrauma 29:1096–1104PubMedPubMedCentralCrossRefGoogle Scholar
  197. 197.
    Zhang Z, Zoltewicz JS, Mondello S, Newsom KJ, Yang Z, Yang B, Kobeissy F, Guingab J, Glushakova O, Robicsek S, Heaton S, Buki A, Hannay J, Gold MS, Rubenstein R, Lu XC, Dave JR, Schmid K, Tortella F, Robertson CS, Wang KK (2014) Human traumatic brain injury induces autoantibody response against glial fibrillary acidic protein and its breakdown products. PLoS One 9:e92698PubMedPubMedCentralCrossRefGoogle Scholar
  198. 198.
    Wang KK, Yang Z, Yue JK, Zhang Z, Winkler EA, Puccio AM, Diaz-Arrastia R, Lingsma HF, Yuh EL, Mukherjee P, Valadka AB, Gordon WA, Okonkwo DO, Manley GT, Cooper SR, Dams-O'Connor K, Hricik AJ, Inoue T, Maas AI, Menon DK, Schnyer DM, Sinha TK, Vassar MJ (2016) Plasma anti-glial fibrillary acidic protein autoantibody levels during the acute and chronic phases of traumatic brain injury: a transforming research and clinical knowledge in traumatic brain injury pilot study. J Neurotrauma 33:1270–1277PubMedCrossRefGoogle Scholar
  199. 199.
    Porter AG, Janicke RU (1999) Emerging roles of caspase-3 in apoptosis. Cell Death Differ 6:99–104PubMedCrossRefGoogle Scholar
  200. 200.
    Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35:495–516PubMedPubMedCentralCrossRefGoogle Scholar
  201. 201.
    Li H, Zhu H, Xu CJ, Yuan J (1998) Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 94:491–501PubMedCrossRefGoogle Scholar
  202. 202.
    Zou H, Li Y, Liu X, Wang X (1999) An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9. J Biol Chem 274:11549–11556PubMedCrossRefGoogle Scholar
  203. 203.
    Lau A, Arundine M, Sun HS, Jones M, Tymianski M (2006) Inhibition of caspase-mediated apoptosis by peroxynitrite in traumatic brain injury. J Neurosci 26:11540–11553PubMedCrossRefGoogle Scholar
  204. 204.
    Lazebnik YA, Kaufmann SH, Desnoyers S, Poirier GG, Earnshaw WC (1994) Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE. Nature 371:346–347PubMedCrossRefGoogle Scholar
  205. 205.
    Tao X, Chen X, Hao S, Hou Z, Lu T, Sun M, Liu B (2015) Protective actions of PJ34, a poly(ADP-ribose)polymerase inhibitor, on the blood-brain barrier after traumatic brain injury in mice. Neuroscience 291:26–36PubMedCrossRefGoogle Scholar
  206. 206.
    Stoica BA, Loane DJ, Zhao Z, Kabadi SV, Hanscom M, Byrnes KR, Faden AI (2014) PARP-1 inhibition attenuates neuronal loss, microglia activation and neurological deficits after traumatic brain injury. J Neurotrauma 31:758–772PubMedPubMedCentralCrossRefGoogle Scholar
  207. 207.
    Wang Y, Lopez D, Davey PG, Cameron DJ, Nguyen K, Tran J, Marquez E, Liu Y, Bi X, Baudry M (2016) Calpain-1 and calpain-2 play opposite roles in retinal ganglion cell degeneration induced by retinal ischemia/reperfusion injury. Neurobiol Dis 93:121–128PubMedCrossRefGoogle Scholar
  208. 208.
    Wang Y, Briz V, Chishti A, Bi X, Baudry M (2013) Distinct roles for mu-calpain and m-calpain in synaptic NMDAR-mediated neuroprotection and extrasynaptic NMDAR-mediated neurodegeneration. J Neurosci 33:18880–18892PubMedPubMedCentralCrossRefGoogle Scholar
  209. 209.
    Morrison RS, Kinoshita Y, Johnson MD, Ghatan S, Ho JT, Garden G (2002) Neuronal survival and cell death signaling pathways. Adv Exp Med Biol 513:41–86PubMedCrossRefGoogle Scholar
  210. 210.
    Stoica BA, Byrnes KR, Faden AI (2009) Cell cycle activation and CNS injury. Neurotox Res 16:221–237PubMedCrossRefGoogle Scholar
  211. 211.
    Di Giovanni S, Movsesyan V, Ahmed F, Cernak I, Schinelli S, Stoica B, Faden AI (2005) Cell cycle inhibition provides neuroprotection and reduces glial proliferation and scar formation after traumatic brain injury. Proc Natl Acad Sci U S A 102:8333–8338PubMedPubMedCentralCrossRefGoogle Scholar
  212. 212.
    Cernak I, Stoica B, Byrnes KR, Di Giovanni S, Faden AI (2005) Role of the cell cycle in the pathobiology of central nervous system trauma. Cell Cycle 4:1286–1293PubMedCrossRefGoogle Scholar
  213. 213.
    Dammer EB, Fallini C, Gozal YM, Duong DM, Rossoll W, Xu P, Lah JJ, Levey AI, Peng J, Bassell GJ, Seyfried NT (2012) Coaggregation of RNA-binding proteins in a model of TDP-43 proteinopathy with selective RGG motif methylation and a role for RRM1 ubiquitination. PLoS One 7:e38658PubMedPubMedCentralCrossRefGoogle Scholar
  214. 214.
    Arai T, Mackenzie IR, Hasegawa M, Nonoka T, Niizato K, Tsuchiya K, Iritani S, Onaya M, Akiyama H (2009) Phosphorylated TDP-43 in Alzheimer’s disease and dementia with Lewy bodies. Acta Neuropathol 117:125–136PubMedCrossRefGoogle Scholar
  215. 215.
    Schwab C, Arai T, Hasegawa M, Yu S, McGeer PL (2008) Colocalization of transactivation-responsive DNA-binding protein 43 and huntingtin in inclusions of Huntington disease. J Neuropathol Exp Neurol 67:1159–1165PubMedCrossRefGoogle Scholar
  216. 216.
    Yokota O, Tsuchiya K, Arai T, Yagishita S, Matsubara O, Mochizuki A, Tamaoka A, Kawamura M, Yoshida H, Terada S, Ishizu H, Kuroda S, Akiyama H (2009) Clinicopathological characterization of Pick’s disease versus frontotemporal lobar degeneration with ubiquitin/TDP-43-positive inclusions. Acta Neuropathol 117:429–444PubMedCrossRefGoogle Scholar
  217. 217.
    van Eersel J, Ke YD, Gladbach A, Bi M, Gotz J, Kril JJ, Ittner LM (2011) Cytoplasmic accumulation and aggregation of TDP-43 upon proteasome inhibition in cultured neurons. PLoS One 6:e22850PubMedPubMedCentralCrossRefGoogle Scholar
  218. 218.
    Yang Z, Lin F, Robertson CS, Wang KK (2014) Dual vulnerability of TDP-43 to calpain and caspase-3 proteolysis after neurotoxic conditions and traumatic brain injury. J Cereb Blood Flow Metab 34:1444–1452PubMedPubMedCentralCrossRefGoogle Scholar
  219. 219.
    Rohn TT (2008) Caspase-cleaved TAR DNA-binding protein-43 is a major pathological finding in Alzheimer’s disease. Brain Res 1228:189–198PubMedPubMedCentralCrossRefGoogle Scholar
  220. 220.
    Rohn TT, Kokoulina P (2009) Caspase-cleaved TAR DNA-binding protein-43 in Pick’s disease. Int J Physiol Pathophysiology Pharmacol 1:25–32Google Scholar
  221. 221.
    Thompson SN, Gibson TR, Thompson BM, Deng Y, Hall ED (2006) Relationship of calpain-mediated proteolysis to the expression of axonal and synaptic plasticity markers following traumatic brain injury in mice. Exp Neurol 201:253–265PubMedCrossRefGoogle Scholar
  222. 222.
    Thomas DG, Palfreyman JW, Ratcliffe JG (1978) Serum-myelin-basic-protein assay in diagnosis and prognosis of patients with head injury. Lancet 1:113–115PubMedCrossRefGoogle Scholar
  223. 223.
    Ottens AK, Golden EC, Bustamante L, Hayes RL, Denslow ND, Wang KK (2008) Proteolysis of multiple myelin basic protein isoforms after neurotrauma: characterization by mass spectrometry. J Neurochem 104:1404–1414PubMedCrossRefGoogle Scholar
  224. 224.
    Liu MC, Akle V, Zheng W, Kitlen J, O'Steen B, Larner SF, Dave JR, Tortella FC, Hayes RL, Wang KK (2006) Extensive degradation of myelin basic protein isoforms by calpain following traumatic brain injury. J Neurochem 98:700–712PubMedCrossRefGoogle Scholar
  225. 225.
    Liu X, Zou H, Slaughter C, Wang X (1997) DFF, a heterodimeric protein that functions downstream of caspase-3 to trigger DNA fragmentation during apoptosis. Cell 89:175–184PubMedCrossRefGoogle Scholar
  226. 226.
    Liu X, Li P, Widlak P, Zou H, Luo X, Garrard WT, Wang X (1998) The 40-kDa subunit of DNA fragmentation factor induces DNA fragmentation and chromatin condensation during apoptosis. Proc Natl Acad Sci U S A 95:8461–8466PubMedPubMedCentralCrossRefGoogle Scholar
  227. 227.
    Zhang C, Raghupathi R, Saatman KE, LaPlaca MC, McIntosh TK (1999) Regional and temporal alterations in DNA fragmentation factor (DFF)-like proteins following experimental brain trauma in the rat. J Neurochem 73:1650–1659PubMedCrossRefGoogle Scholar
  228. 228.
    Feng Y, Cui Y, Gao JL, Li R, Jiang XH, Tian YX, Wang KJ, Li MH, Zhang HA, Cui JZ (2016) Neuroprotective effects of resveratrol against traumatic brain injury in rats: Involvement of synaptic proteins and neuronal autophagy. Mol Med Rep 13:5248–5254PubMedGoogle Scholar
  229. 229.
    Park K, Biederer T (2013) Neuronal adhesion and synapse organization in recovery after brain injury. Future Neurol 8:555–567PubMedPubMedCentralCrossRefGoogle Scholar
  230. 230.
    Walker KR, Tesco G (2013) Molecular mechanisms of cognitive dysfunction following traumatic brain injury. Front Aging Neurosci 5:29PubMedPubMedCentralCrossRefGoogle Scholar
  231. 231.
    Yin TC, Britt JK, De Jesus-Cortes H, Lu Y, Genova RM, Khan MZ, Voorhees JR, Shao J, Katzman AC, Huntington PJ, Wassink C, McDaniel L, Newell EA, Dutca LM, Naidoo J, Cui H, Bassuk AG, Harper MM, McKnight SL, Ready JM, Pieper AA (2014) P7C3 neuroprotective chemicals block axonal degeneration and preserve function after traumatic brain injury. Cell Rep 8:1731–1740PubMedPubMedCentralCrossRefGoogle Scholar
  232. 232.
    Harish G, Mahadevan A, Pruthi N, Sreenivasamurthy SK, Puttamallesh VN, Keshava Prasad TS, Shankar SK, Srinivas Bharath MM (2015) Characterization of traumatic brain injury in human brains reveals distinct cellular and molecular changes in contusion and pericontusion. J Neurochem 134:156–172PubMedCrossRefGoogle Scholar
  233. 233.
    Bales JW, Wagner AK, Kline AE, Dixon CE (2009) Persistent cognitive dysfunction after traumatic brain injury: A dopamine hypothesis. Neurosci Biobehav Rev 33:981–1003PubMedPubMedCentralCrossRefGoogle Scholar
  234. 234.
    Gao X, Deng P, Xu ZC, Chen J (2011) Moderate traumatic brain injury causes acute dendritic and synaptic degeneration in the hippocampal dentate gyrus. PLoS One 6:e24566PubMedPubMedCentralCrossRefGoogle Scholar
  235. 235.
    Zhang B, Chen X, Lin Y, Tan T, Yang Z, Dayao C, Liu L, Jiang R, Zhang J (2011) Impairment of synaptic plasticity in hippocampus is exacerbated by methylprednisolone in a rat model of traumatic brain injury. Brain Res 1382:165–172PubMedCrossRefGoogle Scholar
  236. 236.
    Jourdi H, Lu X, Yanagihara T, Lauterborn JC, Bi X, Gall CM, Baudry M (2005) Prolonged positive modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors induces calpain-mediated PSD-95/Dlg/ZO-1 protein degradation and AMPA receptor down-regulation in cultured hippocampal slices. J Pharmacol Exp Ther 314:16–26PubMedCrossRefGoogle Scholar
  237. 237.
    Xu W, Tse YC, Dobie FA, Baudry M, Craig AM, Wong TP, Wang YT (2013) Simultaneous monitoring of presynaptic transmitter release and postsynaptic receptor trafficking reveals an enhancement of presynaptic activity in metabotropic glutamate receptor-mediated long-term depression. J Neurosci 33:5867–5877PubMedPubMedCentralCrossRefGoogle Scholar
  238. 238.
    Amini M, Ma CL, Farazifard R, Zhu G, Zhang Y, Vanderluit J, Zoltewicz JS, Hage F, Savitt JM, Lagace DC, Slack RS, Beique JC, Baudry M, Greer PA, Bergeron R, Park DS (2013) Conditional disruption of calpain in the CNS alters dendrite morphology, impairs LTP, and promotes neuronal survival following injury. J Neurosci 33:5773–5784PubMedPubMedCentralCrossRefGoogle Scholar
  239. 239.
    Jourdi H (2014) Biomarkers for differential calpain activation in healthy and diseased brains: a systematic review. In: Kevin KW, Wang ZZ, Kobeissy FH (eds) Biomarkers of brain injury and neurological disorders. CRC Press, USA, pp 154–218Google Scholar
  240. 240.
    Robinson S, Winer JL, Berkner J, Chan LA, Denson JL, Maxwell JR, Yang Y, Sillerud LO, Tasker RC, Meehan WP 3rd, Mannix R, Jantzie LL (2016) Imaging and serum biomarkers reflecting the functional efficacy of extended erythropoietin treatment in rats following infantile traumatic brain injury. J Neurosurg Pediatr 17(6):739–745PubMedPubMedCentralCrossRefGoogle Scholar
  241. 241.
    Puskarjov M, Ahmad F, Kaila K, Blaesse P (2012) Activity-dependent cleavage of the K-Cl cotransporter KCC2 mediated by calcium-activated protease calpain. J Neurosci 32:11356–11364PubMedCrossRefGoogle Scholar
  242. 242.
    Cao W, Duan J, Wang X, Zhong X, Hu Z, Huang F, Wang H, Zhang J, Li F, Zhang J, Luo X, Li CQ (2014) Early enriched environment induces an increased conversion of proBDNF to BDNF in the adult rat’s hippocampus. Behav Brain Res 265:76–83PubMedCrossRefGoogle Scholar
  243. 243.
    Jia F, Pan YH, Mao Q, Liang YM, Jiang JY (2010) Matrix metalloproteinase-9 expression and protein levels after fluid percussion injury in rats: the effect of injury severity and brain temperature. J Neurotrauma 27:1059–1068PubMedCrossRefGoogle Scholar
  244. 244.
    Hadass O, Tomlinson BN, Gooyit M, Chen S, Purdy JJ, Walker JM, Zhang C, Giritharan AB, Purnell W, Robinson CR 2nd, Shin D, Schroeder VA, Suckow MA, Simonyi A, Sun GY, Mobashery S, Cui J, Chang M, Gu Z (2013) Selective inhibition of matrix metalloproteinase-9 attenuates secondary damage resulting from severe traumatic brain injury. PLoS One 8:e76904PubMedPubMedCentralCrossRefGoogle Scholar
  245. 245.
    Grossetete M, Phelps J, Arko L, Yonas H, Rosenberg GA (2009) Elevation of matrix metalloproteinases 3 and 9 in cerebrospinal fluid and blood in patients with severe traumatic brain injury. Neurosurgery 65:702–708PubMedPubMedCentralCrossRefGoogle Scholar
  246. 246.
    Shigemori Y, Katayama Y, Mori T, Maeda T, Kawamata T (2006) Matrix metalloproteinase-9 is associated with blood-brain barrier opening and brain edema formation after cortical contusion in rats. Acta Neurochir Suppl 96:130–133PubMedCrossRefGoogle Scholar
  247. 247.
    Bajor M, Michaluk P, Gulyassy P, Kekesi AK, Juhasz G, Kaczmarek L (2012) Synaptic cell adhesion molecule-2 and collapsin response mediator protein-2 are novel members of the matrix metalloproteinase-9 degradome. J Neurochem 122:775–788PubMedCrossRefGoogle Scholar
  248. 248.
    Zhang Z, Ottens AK, Sadasivan S, Kobeissy FH, Fang T, Hayes RL, Wang KK (2007) Calpain-mediated collapsin response mediator protein-1, -2, and -4 proteolysis after neurotoxic and traumatic brain injury. J Neurotrauma 24:460–472PubMedCrossRefGoogle Scholar
  249. 249.
    Thal SC, Luh C, Schaible EV, Timaru-Kast R, Hedrich J, Luhmann HJ, Engelhard K, Zehendner CM (2012) Volatile anesthetics influence blood-brain barrier integrity by modulation of tight junction protein expression in traumatic brain injury. PLoS One 7:e50752PubMedPubMedCentralCrossRefGoogle Scholar
  250. 250.
    Manaenko A, Lekic T, Sozen T, Tsuchiyama R, Zhang JH, Tang J (2009) Effect of gap junction inhibition on intracerebral hemorrhage-induced brain injury in mice. Neurol Res 31:173–178PubMedCrossRefGoogle Scholar
  251. 251.
    Unterberg AW, Stover J, Kress B, Kiening KL (2004) Edema and brain trauma. Neuroscience 129:1021–1029PubMedCrossRefGoogle Scholar
  252. 252.
    McAllister TW (2011) Neurobiological consequences of traumatic brain injury. Dialogues Clin Neurosci 13:287–300PubMedPubMedCentralGoogle Scholar
  253. 253.
    Reichardt HM, Gold R, Luhder F (2006) Glucocorticoids in multiple sclerosis and experimental autoimmune encephalomyelitis. Expert Rev Neurother 6:1657–1670PubMedCrossRefGoogle Scholar
  254. 254.
    Li YH, Zhang CL, Zhang XY, Zhou HX, Meng LL (2015) Effects of mild induced hypothermia on hippocampal connexin 43 and glutamate transporter 1 expression following traumatic brain injury in rats. Mol Med Rep 11:1991–1996PubMedGoogle Scholar
  255. 255.
    Avila MA, Sell SL, Hawkins BE, Hellmich HL, Boone DR, Crookshanks JM, Prough DS, DeWitt DS (2011) Cerebrovascular connexin expression: effects of traumatic brain injury. J Neurotrauma 28:1803–1811PubMedPubMedCentralCrossRefGoogle Scholar
  256. 256.
    Iyyathurai J, Decuypere JP, Leybaert L, D'Hondt C, Bultynck G (2016) Connexins: substrates and regulators of autophagy. BMC Cell Biol 17(Suppl 1):20PubMedPubMedCentralCrossRefGoogle Scholar
  257. 257.
    Sun LQ, Gao JL, Cui CM, Cui Y, Jing XB, Zhao MM, Wang YC, Tian YX, Wang KJ, Cui JZ (2014) Astrocytic p-connexin 43 regulates neuronal autophagy in the hippocampus following traumatic brain injury in rats. Mol Med Rep 9:77–82PubMedGoogle Scholar
  258. 258.
    Sun LQ, Gao JL, Cui Y, Zhao MM, Jing XB, Li R, Tian YX, Cui JZ, Wu ZX (2015) Neuronic autophagy contributes to p-connexin 43 degradation in hippocampal astrocytes following traumatic brain injury in rats. Mol Med Rep 11:4419–4423PubMedGoogle Scholar
  259. 259.
    Thal SC, Schaible EV, Neuhaus W, Scheffer D, Brandstetter M, Engelhard K, Wunder C, Forster CY (2013) Inhibition of proteasomal glucocorticoid receptor degradation restores dexamethasone-mediated stabilization of the blood-brain barrier after traumatic brain injury. Crit Care Med 41:1305–1315PubMedCrossRefGoogle Scholar
  260. 260.
    Sun KJ, Zhu L, Wang HD, Ji XJ, Pan H, Chen M, Lu TJ, Fan YW, Cheng HL, Hang CH, Shi JX (2013) Zinc as mediator of ubiquitin conjugation following traumatic brain injury. Brain Res 1506:132–141PubMedCrossRefGoogle Scholar
  261. 261.
    Zhu L, Ji XJ, Wang HD, Pan H, Chen M, Lu TJ (2012) Zinc neurotoxicity to hippocampal neurons in vitro induces ubiquitin conjugation that requires p38 activation. Brain Res 1438:1–7PubMedCrossRefGoogle Scholar
  262. 262.
    Park Y, Liu C, Luo T, Dietrich WD, Bramlett H, Hu B (2015) Chaperone-mediated autophagy after traumatic brain injury. J Neurotrauma 32:1449–1457PubMedPubMedCentralCrossRefGoogle Scholar
  263. 263.
    Takeichi M, Abe K (2005) Synaptic contact dynamics controlled by cadherin and catenins. Trends Cell Biol 15:216–221PubMedCrossRefGoogle Scholar
  264. 264.
    Lee JH, Lee EO, Kang JL, Chong YH (2008) Concomitant degradation of beta-catenin and GSK-3 beta potently contributes to glutamate-induced neurotoxicity in rat hippocampal slice cultures. J Neurochem 106:1066–1077PubMedCrossRefGoogle Scholar
  265. 265.
    Okabe T, Nakamura T, Nishimura YN, Kohu K, Ohwada S, Morishita Y, Akiyama T (2003) RICS, a novel GTPase-activating protein for Cdc42 and Rac1, is involved in the beta-catenin-N-cadherin and N-methyl-d-aspartate receptor signaling. J Biol Chem 278:9920–9927PubMedCrossRefGoogle Scholar
  266. 266.
    Warren KM, Reeves TM, Phillips LL (2012) MT5-MMP, ADAM-10, and N-cadherin act in concert to facilitate synapse reorganization after traumatic brain injury. J Neurotrauma 29:1922–1940PubMedPubMedCentralCrossRefGoogle Scholar
  267. 267.
    Jang YN, Jung YS, Lee SH, Moon CH, Kim CH, Baik EJ (2009) Calpain-mediated N-cadherin proteolytic processing in brain injury. J Neurosci 29:5974–5984PubMedCrossRefGoogle Scholar
  268. 268.
    Covault J, Liu QY, el-Deeb S (1991) Calcium-activated proteolysis of intracellular domains in the cell adhesion molecules NCAM and N-cadherin. Brain Res Mol Brain Res 11:11–16PubMedCrossRefGoogle Scholar
  269. 269.
    Zhu H, Yoshimoto T, Yamashima T (2014) Heat shock protein 70.1 (Hsp70.1) affects neuronal cell fate by regulating lysosomal acid sphingomyelinase. J Biol Chem 289:27432–27443PubMedPubMedCentralCrossRefGoogle Scholar
  270. 270.
    Yamashima T (2012) Hsp70.1 and related lysosomal factors for necrotic neuronal death. J Neurochem 120:477–494PubMedCrossRefGoogle Scholar
  271. 271.
    Yamashima, T. (2016) Can ‘calpain-cathepsin hypothesis’ explain Alzheimer neuronal death? . Ageing Res Rev. 32:169-179Google Scholar
  272. 272.
    Luo CL, Chen XP, Li LL, Li QQ, Li BX, Xue AM, Xu HF, Dai DK, Shen YW, Tao LY, Zhao ZQ (2013) Poloxamer 188 attenuates in vitro traumatic brain injury-induced mitochondrial and lysosomal membrane permeabilization damage in cultured primary neurons. J Neurotrauma 30:597–607PubMedCrossRefGoogle Scholar
  273. 273.
    Choi JH, Kim DH, Yun IJ, Chang JH, Chun BG, Choi SH (2007) Zaprinast inhibits hydrogen peroxide-induced lysosomal destabilization and cell death in astrocytes. Eur J Pharmacol 571:106–115PubMedCrossRefGoogle Scholar
  274. 274.
    Choi SH, Choi DH, Lee JJ, Park MS, Chun BG (2002) Imidazoline drugs stabilize lysosomes and inhibit oxidative cytotoxicity in astrocytes. Free Radic Biol Med 32:394–405PubMedCrossRefGoogle Scholar
  275. 275.
    Luo C-L, Chen X-P, Yang R, Sun Y-X, Li Q-Q, Bao H-J, Cao Q-Q, Ni H, Qin Z-H, Tao L-Y (2010) Cathepsin B contributes to traumatic brain injury-induced cell death through a mitochondria-mediated apoptotic pathway. J Neurosci Res 88:2847–2858PubMedGoogle Scholar
  276. 276.
    Hook GR, Yu J, Sipes N, Pierschbacher MD, Hook V, Kindy MS (2014) The cysteine protease cathepsin B is a key drug target and cysteine protease inhibitors are potential therapeutics for traumatic brain injury. J Neurotrauma 31:515–529PubMedPubMedCentralCrossRefGoogle Scholar
  277. 277.
    Hook G, Jacobsen JS, Grabstein K, Kindy M, Hook V (2015) Cathepsin B is a new drug target for traumatic brain injury therapeutics: evidence for E64d as a promising lead drug candidate. Front Neurol 6:178PubMedPubMedCentralCrossRefGoogle Scholar
  278. 278.
    Martinez-Vargas M, Soto-Nunez M, Tabla-Ramon E, Solis B, Gonzalez-Rivera R, Perez-Arredondo A, Estrada-Rojo F, Castell A, Molina-Guarneros J, Navarro L (2014) Cystatin C has a dual role in post-traumatic brain injury recovery. Int J Mol Sci 15:5807–5820PubMedPubMedCentralCrossRefGoogle Scholar
  279. 279.
    Lafrenaye AD, McGinn MJ, Povlishock JT (2012) Increased intracranial pressure after diffuse traumatic brain injury exacerbates neuronal somatic membrane poration but not axonal injury: evidence for primary intracranial pressure-induced neuronal perturbation. J Cereb Blood Flow Metab 32:1919–1932PubMedPubMedCentralCrossRefGoogle Scholar
  280. 280.
    Zhang YB, Chen XP, Tao LY, Qin ZH, Li SX, Yang L, Yang J, Zhang YG, Liu R (2006) Expression of cathepsin-B and -D in rat’s brain after traumatic brain injury. Fa Yi Xue Za Zhi 22:404–406. 410PubMedGoogle Scholar
  281. 281.
    Sarkar C, Zhao Z, Aungst S, Sabirzhanov B, Faden AI, Lipinski MM (2014) Impaired autophagy flux is associated with neuronal cell death after traumatic brain injury. Autophagy 10:2208–2222PubMedCrossRefGoogle Scholar
  282. 282.
    Yu Z, Persson HL, Eaton JW, Brunk UT (2003) Intralysosomal iron: a major determinant of oxidant-induced cell death. Free Radic Biol Med 34:1243–1252PubMedCrossRefGoogle Scholar
  283. 283.
    Yu ZQ, Jia Y, Chen G (2014) Possible involvement of cathepsin B/D and caspase-3 in deferoxamine-related neuroprotection of early brain injury after subarachnoid haemorrhage in rats. Neuropathol Appl Neurobiol 40:270–283PubMedCrossRefGoogle Scholar
  284. 284.
    Kontoghiorghes GJ, Pattichi K, Hadjigavriel M, Kolnagou A (2000) Transfusional iron overload and chelation therapy with deferoxamine and deferiprone (L1). Transfus Sci 23:211–223PubMedCrossRefGoogle Scholar
  285. 285.
    Seifert A, von Herrath D, Schaefer K (1987) Iron overload, but not treatment with desferrioxamine favours the development of septicemia in patients on maintenance hemodialysis. Q J Med 65:1015–1024PubMedGoogle Scholar
  286. 286.
    Xu J, Wang H, Ding K, Lu X, Li T, Wang J, Wang C, Wang J (2013) Inhibition of cathepsin S produces neuroprotective effects after traumatic brain injury in mice. Mediators Inflamm 2013:11Google Scholar
  287. 287.
    Ni J, Wu Z, Peterts C, Yamamoto K, Qing H, Nakanishi H (2015) The critical role of proteolytic relay through cathepsins B and E in the phenotypic change of microglia/macrophage. J Neurosci 35:12488–12501PubMedCrossRefGoogle Scholar
  288. 288.
    Zhang L, Dittmer MR, Blackwell K, Workman LM, Hostager B, Habelhah H (2015) TRAIL activates JNK and NF-kappaB through RIP1-dependent and -independent pathways. Cell Signal 27:306–314PubMedCrossRefGoogle Scholar
  289. 289.
    Rao NV, Rao GV, Hoidal JR (1997) Human dipeptidyl-peptidase I. Gene characterization, localization, and expression. J Biol Chem 272:10260–10265PubMedCrossRefGoogle Scholar
  290. 290.
    Fan K, Wu X, Fan B, Li N, Lin Y, Yao Y, Ma J (2012) Up-regulation of microglial cathepsin C expression and activity in lipopolysaccharide-induced neuroinflammation. J Neuroinflammation 9:96PubMedPubMedCentralCrossRefGoogle Scholar
  291. 291.
    Koike M, Shibata M, Ezaki J, Peters C, Saftig P, Kominami E, Uchiyama Y (2013) Differences in expression patterns of cathepsin C/dipeptidyl peptidase I in normal, pathological and aged mouse central nervous system. Eur J Neurosci 37:816–830PubMedCrossRefGoogle Scholar
  292. 292.
    Kanbak G, Kartkaya K, Ozcelik E, Guvenal AB, Kabay SC, Arslan G, Durmaz R (2013) The neuroprotective effect of acute moderate alcohol consumption on caspase-3 mediated neuroapoptosis in traumatic brain injury: the role of lysosomal cathepsin L and nitric oxide. Gene 512:492–495PubMedCrossRefGoogle Scholar
  293. 293.
    Ma Y, Matsuwaki T, Yamanouchi K, Nishihara M (2016) Progranulin protects hippocampal neurogenesis via suppression of neuroinflammatory responses under acute immune stress. Mol Neurobiol. doi:10.1007/s12035-016-9939-6Google Scholar
  294. 294.
    Tanaka Y, Matsuwaki T, Yamanouchi K, Nishihara M (2013) Increased lysosomal biogenesis in activated microglia and exacerbated neuronal damage after traumatic brain injury in progranulin-deficient mice. Neuroscience 250:8–19PubMedCrossRefGoogle Scholar
  295. 295.
    Raabe A, Seifert V (1999) Fatal secondary increase in serum S-100B protein after severe head injury. Report of three cases. J Neurosurg 91:875–877PubMedCrossRefGoogle Scholar
  296. 296.
    Vos PE, Lamers KJ, Hendriks JC, van Haaren M, Beems T, Zimmerman C, van Geel W, de Reus H, Biert J, Verbeek MM (2004) Glial and neuronal proteins in serum predict outcome after severe traumatic brain injury. Neurology 62:1303–1310PubMedCrossRefGoogle Scholar
  297. 297.
    Inao S, Marmarou A, Clarke GD, Andersen BJ, Fatouros PP, Young HF (1988) Production and clearance of lactate from brain tissue, cerebrospinal fluid, and serum following experimental brain injury. J Neurosurg 69:736–744PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media LLC 2017

Authors and Affiliations

  • Hadi Abou-El-Hassan
    • 1
  • Fares Sukhon
    • 2
  • Edwyn Jeremy Assaf
    • 1
  • Hisham Bahmad
    • 3
    • 4
  • Hussein Abou-Abbass
    • 5
    • 6
  • Hussam Jourdi
    • 7
  • Firas H. Kobeissy
    • 8
    • 9
  1. 1.Faculty of MedicineAmerican University of Beirut Medical CenterBeirutLebanon
  2. 2.Faculty of Medicine, Department of Internal MedicineAmerican University of Beirut Medical CenterBeirutLebanon
  3. 3.Faculty of Medical, Neuroscience Research CenterBeirut Arab UniversityBeirutLebanon
  4. 4.Faculty of Medicine, Department of Anatomy, Cell Biology and Physiological SciencesAmerican University of BeirutBeirutLebanon
  5. 5.Faculty of Medical Sciences, Neuroscience Research CenterLebanese UniversityBeirutLebanon
  6. 6.Faculty of Medicine, Department of Biochemistry and Molecular GeneticsAmerican University of BeirutBeirutLebanon
  7. 7.Faculty of Science¸ Department of BiologyUniversity of BalamandAleyLebanon
  8. 8.Faculty of Medicine, Department of Biochemistry and Molecular GeneticsAmerican University of BeirutBeirutLebanon
  9. 9.Department of Psychiatry, Center for Neuroproteomics and Biomarkers ResearchUniversity of FloridaGainesvilleUSA

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