How Do Subcellular Organelles Participate in Preconditioning-Conferred Neuroprotection?

  • Peiying LiEmail author
  • Rehana Leak
  • Yu Gan
  • Xiaoming Hu
  • R. Anne Stetler
  • Jun Chen
Part of the Springer Series in Translational Stroke Research book series (SSTSR)


Preconditioning or tolerance is a natural phenomenon of endogenous adaptation, whereby subtoxic stress protects against subsequent higher dose stress. Although preconditioning is likely to be a ubiquitous stress response relevant to many disease conditions, it has been most successfully employed in ischemia research. Enormous efforts have focused on identifying the intrinsic mechanisms so that they can be translated into pharmacological interventions aimed at counteracting neurodegeneration following stroke. A firm grasp of the molecular events at the level of each subcellular organelle will aid researchers to move closer towards this elusive clinical goal. Fortunately, technological innovations such as the confocal and transmission electron microscopes have transported preconditioning research into the subcellular organelle level. This has deepened our knowledge of how preconditioning affects these organelles and triggers subcellular signaling pathways that eventually lead to neuroprotective processes and cellular survival. In this chapter, the participation of mitochondria, the endoplasmic reticulum, proteasomes, lysosomes, the Golgi apparatus, the peroxisome proliferator-activated receptors on the nuclear membrane, and gene expression regulating factors in the nucleus will thus be considered.


Endoplasmic Reticulum Stress Reactive Oxygen Species Generation Unfold Protein Response Ischemic Precondition Mitochondrial Biogenesis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Adamczyk S, Robin E et al (2010) Sevoflurane pre- and post-conditioning protect the brain via the mitochondrial K ATP channel. Br J Anaesth 104(2):191–200PubMedCrossRefGoogle Scholar
  2. Aoki M, Tamatani M et al (2001) Hypothermic treatment restores glucose regulated protein 78 (GRP78) expression in ischemic brain. Brain Res Mol Brain Res 95(1–2):117–128PubMedCrossRefGoogle Scholar
  3. Baek SH, Kim JY et al (2000) Reduced glutathione oxidation ratio and 8 ohdG accumulation by mild ischemic pretreatment. Brain Res 856(1–2):28–36PubMedCrossRefGoogle Scholar
  4. Baines CP, Zhang J et al (2002) Mitochondrial PKCepsilon and MAPK form signaling modules in the murine heart: enhanced mitochondrial PKCepsilon-MAPK interactions and differential MAPK activation in PKCepsilon-induced cardioprotection. Circ Res 90(4):390–397PubMedCrossRefGoogle Scholar
  5. Baines CP, Song CX et al (2003) Protein kinase cepsilon interacts with and inhibits the permeability transition pore in cardiac mitochondria. Circ Res 92(8):873–880PubMedCrossRefGoogle Scholar
  6. Bajgar R, Seetharaman S et al (2001) Identification and properties of a novel intracellular (mitochondrial) ATP-sensitive potassium channel in brain. J Biol Chem 276(36):33369–33374PubMedCrossRefGoogle Scholar
  7. Balduini W, Carloni S et al (2009) Autophagy in hypoxia-ischemia induced brain injury: evidence and speculations. Autophagy 5(2):221–223PubMedCrossRefGoogle Scholar
  8. Baranova O, Miranda LF et al (2007) Neuron-specific inactivation of the hypoxia inducible factor 1 alpha increases brain injury in a mouse model of transient focal cerebral ischemia. J Neurosci 27(23):6320–6332PubMedCrossRefGoogle Scholar
  9. Berger JP, Akiyama TE et al (2005) PPARs: therapeutic targets for metabolic disease. Trends Pharmacol Sci 26(5):244–251PubMedCrossRefGoogle Scholar
  10. Bergeron M, Gidday JM et al (2000) Role of hypoxia-inducible factor-1 in hypoxia-induced ischemic tolerance in neonatal rat brain. Ann Neurol 48(3):285–296PubMedCrossRefGoogle Scholar
  11. Bernaudin M, Nedelec AS et al (2002a) Normobaric hypoxia induces tolerance to focal permanent cerebral ischemia in association with an increased expression of hypoxia-inducible factor-1 and its target genes, erythropoietin and VEGF, in the adult mouse brain. J Cereb Blood Flow Metab 22(4):393–403PubMedCrossRefGoogle Scholar
  12. Bernaudin M, Tang Y et al (2002b) Brain genomic response following hypoxia and re-oxygenation in the neonatal rat. Identification of genes that might contribute to hypoxia-induced ischemic tolerance. J Biol Chem 277(42):39728–39738PubMedCrossRefGoogle Scholar
  13. Bertoni-Freddari C, Fattoretti P et al (2006) Reactive structural dynamics of synaptic mitochondria in ischemic delayed neuronal death. Ann N Y Acad Sci 1090:26–34PubMedCrossRefGoogle Scholar
  14. Bickler PE, Fahlman CS (2004) Moderate increases in intracellular calcium activate neuroprotective signals in hippocampal neurons. Neuroscience 127(3):673–683PubMedCrossRefGoogle Scholar
  15. Bickler PE, Fahlman CS et al (2009) Inositol 1,4,5-triphosphate receptors and NAD(P)H mediate Ca2+ signaling required for hypoxic preconditioning of hippocampal neurons. Neuroscience 160(1):51–60PubMedCrossRefGoogle Scholar
  16. Bigdeli MR, Khoshbaten A (2008) In vivo preconditioning with normobaric hyperoxia induces ischemic tolerance partly by triggering tumor necrosis factor-alpha converting enzyme/tumor necrosis factor-alpha/nuclear factor-kappaB. Neuroscience 153(3):671–678PubMedCrossRefGoogle Scholar
  17. Blondeau N, Widmann C et al (2001) Activation of the nuclear factor-kappaB is a key event in brain tolerance. J Neurosci 21(13):4668–4677PubMedGoogle Scholar
  18. Boengler K, Dodoni G et al (2005) Connexin 43 in cardiomyocyte mitochondria and its increase by ischemic preconditioning. Cardiovasc Res 67(2):234–244PubMedCrossRefGoogle Scholar
  19. Bordet R, Ouk T et al (2006) PPAR: a new pharmacological target for neuroprotection in stroke and neurodegenerative diseases. Biochem Soc Trans 34(Pt 6):1341–1346PubMedGoogle Scholar
  20. Bouwman RA, Musters RJ et al (2004) Reactive oxygen species precede protein kinase C-delta activation independent of adenosine triphosphate-sensitive mitochondrial channel opening in sevoflurane-induced cardioprotection. Anesthesiology 100(3):506–514PubMedCrossRefGoogle Scholar
  21. Bouwman RA, Musters RJ et al (2007) Sevoflurane-induced cardioprotection depends on PKC-alpha activation via production of reactive oxygen species. Br J Anaesth 99(5):639–645PubMedCrossRefGoogle Scholar
  22. Busija DW, Gaspar T et al (2008) Mitochondrial-mediated suppression of ROS production upon exposure of neurons to lethal stress: mitochondrial targeted preconditioning. Adv Drug Deliv Rev 60(13–14):1471–1477PubMedCrossRefGoogle Scholar
  23. Cao Z, Gao W et al (2009) Thirty-five percent oxygen pre-conditioning protects PC12 cells against death induced by hypoxia. Free Radic Res 43(1):58–67PubMedCrossRefGoogle Scholar
  24. Carloni S, Buonocore G et al (2008) Protective role of autophagy in neonatal hypoxia-ischemia induced brain injury. Neurobiol Dis 32(3):329–339PubMedCrossRefGoogle Scholar
  25. Carreira RS, Lee Y et al (2010) Cyclophilin D is required for mitochondrial removal by autophagy in cardiac cells. Autophagy 6(4)Google Scholar
  26. Chen J, Graham SH et al (1996) Stress proteins and tolerance to focal cerebral ischemia. J Cereb Blood Flow Metab 16(4):566–577PubMedCrossRefGoogle Scholar
  27. Chen H, Hu CJ et al (2001) Reduction and restoration of mitochondrial DNA content after focal cerebral ischemia/reperfusion. Stroke 32(10):2382–2387PubMedCrossRefGoogle Scholar
  28. Chen LJ, Su XW et al (2004) Thermal preconditioning protected cerebellar granule neurons of rats by modulating HSP70 expression. Acta Pharmacol Sin 25(4):458–461PubMedGoogle Scholar
  29. Chen M, Lu TJ et al (2008) Differential roles of NMDA receptor subtypes in ischemic neuronal cell death and ischemic tolerance. Stroke 39(11):3042–3048PubMedCrossRefGoogle Scholar
  30. Cheney JA, Weisser JD et al (2001) The maxi-K channel opener BMS-204352 attenuates regional cerebral edema and neurologic motor impairment after experimental brain injury. J Cereb Blood Flow Metab 21(4):396–403PubMedCrossRefGoogle Scholar
  31. Chi X, Sutton ET et al (2000) Potassium channel openers prevent beta-amyloid toxicity in bovine vascular endothelial cells. Neurosci Lett 290(1):9–12PubMedCrossRefGoogle Scholar
  32. Chong KY, Lai CC et al (1998) Stable overexpression of the constitutive form of heat shock protein 70 confers oxidative protection. J Mol Cell Cardiol 30(3):599–608PubMedCrossRefGoogle Scholar
  33. Chu PW, Beart PM et al (2010) Preconditioning protects against oxidative injury involving hypoxia-inducible factor-1 and vascular endothelial growth factor in cultured astrocytes. Eur J Pharmacol 633(1–3):24–32PubMedCrossRefGoogle Scholar
  34. Churilova AV, Rybnikova EA et al (2010) Effects of moderate hypobaric hypoxic preconditioning on the expression of the transcription factors pCREB and NF-kappaB in the rat hippocampus before and after severe hypoxia. Neurosci Behav Physiol 40(8):852–857PubMedCrossRefGoogle Scholar
  35. Ciechanover A (2006) Intracellular protein degradation: from a vague idea thru the lysosome and the ubiquitin-proteasome system and onto human diseases and drug targeting. Exp Biol Med (Maywood) 231(7):1197–1211Google Scholar
  36. Collino M, Aragno M et al (2006a) Oxidative stress and inflammatory response evoked by transient cerebral ischemia/reperfusion: effects of the PPAR-alpha agonist WY14643. Free Radic Biol Med 41(4):579–589PubMedCrossRefGoogle Scholar
  37. Collino M, Aragno M et al (2006b) Modulation of the oxidative stress and inflammatory response by PPAR-gamma agonists in the hippocampus of rats exposed to cerebral ischemia/reperfusion. Eur J Pharmacol 530(1–2):70–80PubMedCrossRefGoogle Scholar
  38. Currie RW, Ellison JA et al (2000) Benign focal ischemic preconditioning induces neuronal Hsp70 and prolonged astrogliosis with expression of Hsp27. Brain Res 863(1–2):169–181PubMedCrossRefGoogle Scholar
  39. Dharap A, Vemuganti R (2010) Ischemic pre-conditioning alters cerebral microRNAs that are upstream to neuroprotective signaling pathways. J Neurochem 113(6):1685–1691PubMedGoogle Scholar
  40. Dharap A, Bowen K et al (2009) Transient focal ischemia induces extensive temporal changes in rat cerebral microRNAome. J Cereb Blood Flow Metab 29(4):675–687PubMedCrossRefGoogle Scholar
  41. Di Paola R, Cuzzocrea S (2007) Peroxisome proliferator-activated receptors ligands and ischemia-reperfusion injury. Naunyn Schmiedebergs Arch Pharmacol 375(3):157–175PubMedCrossRefGoogle Scholar
  42. Digicaylioglu M, Lipton SA (2001) Erythropoietin-mediated neuroprotection involves cross-talk between Jak2 and NF-kappaB signalling cascades. Nature 412(6847):641–647PubMedCrossRefGoogle Scholar
  43. Dirnagl U, Meisel A (2008) Endogenous neuroprotection: mitochondria as gateways to cerebral preconditioning? Neuropharmacology 55(3):334–344PubMedCrossRefGoogle Scholar
  44. Dirnagl U, Becker K et al (2009) Preconditioning and tolerance against cerebral ischaemia: from experimental strategies to clinical use. Lancet Neurol 8(4):398–412PubMedCrossRefGoogle Scholar
  45. Douglas RM, Lai JC et al (2006) The calcium-sensitive large-conductance potassium channel (BK/MAXI K) is present in the inner mitochondrial membrane of rat brain. Neuroscience 139(4):1249–1261PubMedCrossRefGoogle Scholar
  46. Endres M, Meisel A et al (2000) DNA methyltransferase contributes to delayed ischemic brain injury. J Neurosci 20(9):3175–3181PubMedGoogle Scholar
  47. Falcao AS, Silva RF et al (2007) Influence of hypoxia and ischemia preconditioning on bilirubin damage to astrocytes. Brain Res 1149:191–199PubMedCrossRefGoogle Scholar
  48. Forbes RA, Steenbergen C et al (2001) Diazoxide-induced cardioprotection requires signaling through a redox-sensitive mechanism. Circ Res 88(8):802–809PubMedCrossRefGoogle Scholar
  49. Furuya N, Yu J et al (2005) The evolutionarily conserved domain of Beclin 1 is required for Vps34 binding, autophagy and tumor suppressor function. Autophagy 1(1):46–52PubMedCrossRefGoogle Scholar
  50. Gao Y, Gao G et al (2006) Enhanced phosphorylation of cyclic AMP response element binding protein in the brain of mice following repetitive hypoxic exposure. Biochem Biophys Res Commun 340(2):661–667PubMedCrossRefGoogle Scholar
  51. Gaspar T, Katakam P et al (2008a) Delayed neuronal preconditioning by NS1619 is independent of calcium activated potassium channels. J Neurochem 105(4):1115–1128PubMedCrossRefGoogle Scholar
  52. Gaspar T, Snipes JA et al (2008b) ROS-independent preconditioning in neurons via activation of mitoK(ATP) channels by BMS-191095. J Cereb Blood Flow Metab 28(6):1090–1103PubMedCrossRefGoogle Scholar
  53. Gaspar T, Domoki F et al (2009) Immediate neuronal preconditioning by NS1619. Brain Res 1285:196–207PubMedCrossRefGoogle Scholar
  54. Ge PF, Luo TF et al (2008) Ischemic preconditioning induces chaperone hsp70 expression and inhibits protein aggregation in the CA1 neurons of rats. Neurosci Bull 24(5):288–296PubMedCrossRefGoogle Scholar
  55. Geisler S, Holmstrom KM et al (2010) PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat Cell Biol 12(2):119–131PubMedCrossRefGoogle Scholar
  56. Goldberg AL (2007) Functions of the proteasome: from protein degradation and immune surveillance to cancer therapy. Biochem Soc Trans 35(Pt 1):12–17PubMedGoogle Scholar
  57. Goodman Y, Mattson MP (1996) K+ channel openers protect hippocampal neurons against oxidative injury and amyloid beta-peptide toxicity. Brain Res 706(2):328–332PubMedCrossRefGoogle Scholar
  58. Gu GJ, Li YP et al (2008) Mechanism of ischemic tolerance induced by hyperbaric oxygen preconditioning involves upregulation of hypoxia-inducible factor-1alpha and erythropoietin in rats. J Appl Physiol 104(4):1185–1191PubMedCrossRefGoogle Scholar
  59. Gutsaeva DR, Carraway MS et al (2008) Transient hypoxia stimulates mitochondrial biogenesis in brain subcortex by a neuronal nitric oxide synthase-dependent mechanism. J Neurosci 28(9):2015–2024PubMedCrossRefGoogle Scholar
  60. Halestrap AP (2006) Mitochondria and preconditioning: a connexin connection? Circ Res 99(1):10–12PubMedCrossRefGoogle Scholar
  61. Halestrap AP, Clarke SJ et al (2007) The role of mitochondria in protection of the heart by preconditioning. Biochim Biophys Acta 1767(8):1007–1031PubMedCrossRefGoogle Scholar
  62. Hara T, Hamada J et al (2003) CREB is required for acquisition of ischemic tolerance in gerbil hippocampal CA1 region. J Neurochem 86(4):805–814PubMedCrossRefGoogle Scholar
  63. Hara T, Nakamura K et al (2006) Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441(7095):885–889PubMedCrossRefGoogle Scholar
  64. Hausenloy DJ, Ong SB et al (2009) The mitochondrial permeability transition pore as a target for preconditioning and postconditioning. Basic Res Cardiol 104(2):189–202PubMedCrossRefGoogle Scholar
  65. Hausenloy DJ, Lim SY et al (2010) Mitochondrial cyclophilin-D as a critical mediator of ischaemic preconditioning. Cardiovasc Res 88(1):67–74PubMedCrossRefGoogle Scholar
  66. Hayashi T, Saito A et al (2003) Induction of GRP78 by ischemic preconditioning reduces endoplasmic reticulum stress and prevents delayed neuronal cell death. J Cereb Blood Flow Metab 23(8):949–961PubMedCrossRefGoogle Scholar
  67. He Y, Hua Y et al (2008) Induction of autophagy in rat hippocampus and cultured neurons by iron. Acta Neurochir Suppl 105:29–32PubMedCrossRefGoogle Scholar
  68. Heneka MT, Landreth GE (2007) PPARs in the brain. Biochim Biophys Acta 1771(8):1031–1045PubMedCrossRefGoogle Scholar
  69. Hepp S, Gerich FJ et al (2005) Sulfhydryl oxidation reduces hippocampal susceptibility to hypoxia-induced spreading depression by activating BK channels. J Neurophysiol 94(2):1091–1103PubMedCrossRefGoogle Scholar
  70. Hirata N, Shim YH et al (2011) Isoflurane differentially modulates mitochondrial reactive oxygen species production via forward versus reverse electron transport flow: implications for preconditioning. Anesthesiology 115(3):531–540PubMedCrossRefGoogle Scholar
  71. Hofbauer KH, Gess B et al (2003) Oxygen tension regulates the expression of a group of procollagen hydroxylases. Eur J Biochem 270(22):4515–4522PubMedCrossRefGoogle Scholar
  72. Hofmann PA, Israel M et al (2007) N-Benzyladriamycin-14-valerate (AD 198): a non-cardiotoxic anthracycline that is cardioprotective through PKC-epsilon activation. J Pharmacol Exp Ther 323(2):658–664PubMedCrossRefGoogle Scholar
  73. Hua Y, Keep RF et al (2003) Thrombin preconditioning attenuates brain edema induced by erythrocytes and iron. J Cereb Blood Flow Metab 23(12):1448–1454PubMedCrossRefGoogle Scholar
  74. Huang C, Yitzhaki S et al (2010) Autophagy induced by ischemic preconditioning is essential for cardioprotection. J Cardiovasc Transl Res 3(4):365–373PubMedCrossRefGoogle Scholar
  75. Huang C, Andres AM et al (2011) Preconditioning involves selective mitophagy mediated by Parkin and p62/SQSTM1. PLoS One 6(6):e20975PubMedCrossRefGoogle Scholar
  76. Ikeda T, Xia XY et al (2000) Glial cell line-derived neurotrophic factor protects against ischemia/hypoxia-induced brain injury in neonatal rat. Acta Neuropathol 100(2):161–167PubMedCrossRefGoogle Scholar
  77. Inoue I, Nagase H et al (1991) ATP-sensitive K+ channel in the mitochondrial inner membrane. Nature 352(6332):244–247PubMedCrossRefGoogle Scholar
  78. Jeyaseelan K, Lim KY et al (2008) MicroRNA expression in the blood and brain of rats subjected to transient focal ischemia by middle cerebral artery occlusion. Stroke 39(3):959–966PubMedCrossRefGoogle Scholar
  79. Jhaveri KA, Reichensperger J et al (2007) Reduced basal and lipopolysaccharide-stimulated adenosine A1 receptor expression in the brain of nuclear factor-kappaB p50-/- mice. Neuroscience 146(1):415–426PubMedCrossRefGoogle Scholar
  80. Jiang X, Zhu D et al (2003) N-methyl-D-aspartate and TrkB receptor activation in cerebellar granule cells: an in vitro model of preconditioning to stimulate intrinsic survival pathways in neurons. Ann N Y Acad Sci 993:134–145, discussion 159–160PubMedCrossRefGoogle Scholar
  81. Jones NM, Lee EM et al (2006) Hypoxic preconditioning produces differential expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and its regulatory enzyme HIF prolyl hydroxylase 2 in neonatal rat brain. Neurosci Lett 404(1–2):72–77PubMedCrossRefGoogle Scholar
  82. Juhaszova M, Zorov DB et al (2004) Glycogen synthase kinase-3beta mediates convergence of protection signaling to inhibit the mitochondrial permeability transition pore. J Clin Invest 113(11):1535–1549PubMedGoogle Scholar
  83. Juhaszova M, Wang S et al (2008) The identity and regulation of the mitochondrial permeability transition pore: where the known meets the unknown. Ann N Y Acad Sci 1123:197–212PubMedCrossRefGoogle Scholar
  84. Juhaszova M, Zorov DB et al (2009) Role of glycogen synthase kinase-3beta in cardioprotection. Circ Res 104(11):1240–1252PubMedCrossRefGoogle Scholar
  85. Kaneko T, Yokoyama K et al (2005) Late preconditioning with isoflurane in cultured rat cortical neurones. Br J Anaesth 95(5):662–668PubMedCrossRefGoogle Scholar
  86. Kato H, Kogure K et al (1995) Immunohistochemical localization of the low molecular weight stress protein HSP27 following focal cerebral ischemia in the rat. Brain Res 679(1):1–7PubMedCrossRefGoogle Scholar
  87. Kevin LG, Novalija E et al (2003) Sevoflurane exposure generates superoxide but leads to decreased superoxide during ischemia and reperfusion in isolated hearts. Anesth Analg 96(4):949–955, table of contentsPubMedCrossRefGoogle Scholar
  88. Kis B, Rajapakse NC et al (2003) Diazoxide induces delayed pre-conditioning in cultured rat cortical neurons. J Neurochem 87(4):969–980PubMedCrossRefGoogle Scholar
  89. Komatsu M, Kominami E et al (2006a) Autophagy and neurodegeneration. Autophagy 2(4):315–317PubMedGoogle Scholar
  90. Komatsu M, Waguri S et al (2006b) Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 441(7095):880–884PubMedCrossRefGoogle Scholar
  91. Korolchuk VI, Menzies FM et al (2009) A novel link between autophagy and the ubiquitin-proteasome system. Autophagy 5(6):862–863PubMedGoogle Scholar
  92. Lai Y, Hickey RW et al (2008) Autophagy is increased after traumatic brain injury in mice and is partially inhibited by the antioxidant gamma-glutamylcysteinyl ethyl ester. J Cereb Blood Flow Metab 28(3):540–550PubMedCrossRefGoogle Scholar
  93. Lanneau D, Wettstein G et al (2010) Heat shock proteins: cell protection through protein triage. ScientificWorldJournal 10:1543–1552PubMedCrossRefGoogle Scholar
  94. Lee JA (2009) Autophagy in neurodegeneration: two sides of the same coin. BMB Rep 42(6):324–330PubMedCrossRefGoogle Scholar
  95. Lee HT, Chang YC et al (2009) VEGF-A/VEGFR-2 signaling leading to cAMP response element-binding protein phosphorylation is a shared pathway underlying the protective effect of preconditioning on neurons and endothelial cells. J Neurosci 29(14):4356–4368PubMedCrossRefGoogle Scholar
  96. Lee ST, Chu K et al (2010) MicroRNAs induced during ischemic preconditioning. Stroke 41(8):1646–1651PubMedCrossRefGoogle Scholar
  97. Lehotsky J, Racay P et al (2009a) Cross-talk of intracellular calcium stores in the response to neuronal ischemia and ischemic tolerance. Gen Physiol Biophys 28 Spec No Focus:F104–F114PubMedGoogle Scholar
  98. Lehotsky J, Urban P et al (2009b) Molecular mechanisms leading to neuroprotection/ischemic tolerance: effect of preconditioning on the stress reaction of endoplasmic reticulum. Cell Mol Neurobiol 29(6–7):917–925PubMedCrossRefGoogle Scholar
  99. Lenzser G, Kis B et al (2005) Diazoxide preconditioning attenuates global cerebral ischemia-induced blood-brain barrier permeability. Brain Res 1051(1–2):72–80PubMedCrossRefGoogle Scholar
  100. Lewis BP, Burge CB et al (2005) Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120(1):15–20PubMedCrossRefGoogle Scholar
  101. Li J, Lee B et al (2006a) Endoplasmic reticulum stress-induced apoptosis: multiple pathways and activation of p53-up-regulated modulator of apoptosis (PUMA) and NOXA by p53. J Biol Chem 281(11):7260–7270PubMedCrossRefGoogle Scholar
  102. Li W, Luo Y et al (2006b) Ischemic preconditioning in the rat brain enhances the repair of endogenous oxidative DNA damage by activating the base-excision repair pathway. J Cereb Blood Flow Metab 26(2):181–198PubMedCrossRefGoogle Scholar
  103. Li N, Wu H et al (2007) Ischemic preconditioning induces XRCC1, DNA polymerase-beta, and DNA ligase III and correlates with enhanced base excision repair. DNA Repair (Amst) 6(9):1297–1306CrossRefGoogle Scholar
  104. Li QF, Zhu YS et al (2008a) Isoflurane preconditioning activates HIF-1alpha, iNOS and Erk1/2 and protects against oxygen-glucose deprivation neuronal injury. Brain Res 1245:26–35PubMedCrossRefGoogle Scholar
  105. Li YX, Ding SJ et al (2008b) Desferoxamine preconditioning protects against cerebral ischemia in rats by inducing expressions of hypoxia inducible factor 1 alpha and erythropoietin. Neurosci Bull 24(2):89–95PubMedCrossRefGoogle Scholar
  106. Li J, Xuan W et al (2011a) Remote preconditioning provides potent cardioprotection via PI3K/Akt activation and is associated with nuclear accumulation of beta-catenin. Clin Sci (Lond) 120(10):451–462CrossRefGoogle Scholar
  107. Li P, Hu X et al (2011b) Mechanistic insight into DNA damage and repair in ischemic stroke: exploiting the base excision repair pathway as a model of neuroprotection. Antioxid Redox Signal 14(10):1905–1918PubMedCrossRefGoogle Scholar
  108. Liang HL, Wong-Riley MT (2006) Activity-dependent regulation of nuclear respiratory factor-1, nuclear respiratory factor-2, and peroxisome proliferator-activated receptor gamma coactivator-1 in neurons. Neuroreport 17(4):401–405PubMedCrossRefGoogle Scholar
  109. Liebelt B, Papapetrou P et al (2010) Exercise preconditioning reduces neuronal apoptosis in stroke by up-regulating heat shock protein-70 (heat shock protein-72) and extracellular-signal-regulated-kinase 1/2. Neuroscience 166(4):1091–1100PubMedCrossRefGoogle Scholar
  110. Lim KL (2007) Ubiquitin-proteasome system dysfunction in Parkinson’s disease: current evidence and controversies. Expert Rev Proteomics 4(6):769–781PubMedCrossRefGoogle Scholar
  111. Lim SY, Davidson SM et al (2007) Preconditioning and postconditioning: the essential role of the mitochondrial permeability transition pore. Cardiovasc Res 75(3):530–535PubMedCrossRefGoogle Scholar
  112. Limatola V, Ward P et al (2010) Xenon preconditioning confers neuroprotection regardless of gender in a mouse model of transient middle cerebral artery occlusion. Neuroscience 165(3):874–881PubMedCrossRefGoogle Scholar
  113. Lin JH, Li H et al (2007) IRE1 signaling affects cell fate during the unfolded protein response. Science 318(5852):944–949PubMedCrossRefGoogle Scholar
  114. Lin CH, Chen PS et al (2008) Glutamate preconditioning prevents neuronal death induced by combined oxygen-glucose deprivation in cultured cortical neurons. Eur J Pharmacol 589(1–3):85–93PubMedCrossRefGoogle Scholar
  115. Liu M, Alkayed NJ (2005) Hypoxic preconditioning and tolerance via hypoxia inducible factor (HIF) 1alpha-linked induction of P450 2C11 epoxygenase in astrocytes. J Cereb Blood Flow Metab 25(8):939–948PubMedCrossRefGoogle Scholar
  116. Liu C, Chen S et al (2005a) Ischemic preconditioning prevents protein aggregation after transient cerebral ischemia. Neuroscience 134(1):69–80PubMedCrossRefGoogle Scholar
  117. Liu CL, Ge P et al (2005b) Co-translational protein aggregation after transient cerebral ischemia. Neuroscience 134(4):1273–1284PubMedCrossRefGoogle Scholar
  118. Liu Y, Yang XM et al (2008) Redox signaling at reperfusion is required for protection from ischemic preconditioning but not from a direct PKC activator. Basic Res Cardiol 103(1):54–59PubMedCrossRefGoogle Scholar
  119. Lotz C, Lange M et al (2011a) Peroxisome-proliferator-activated receptor gamma mediates the second window of anaesthetic-induced preconditioning. Exp Physiol 96(3):317–324PubMedCrossRefGoogle Scholar
  120. Lotz C, Lazariotto M et al (2011b) Activation of peroxisome-proliferator-activated receptors alpha and gamma mediates remote ischemic preconditioning against myocardial infarction in vivo. Exp Biol Med (Maywood) 236(1):113–122CrossRefGoogle Scholar
  121. Lusardi TA, Farr CD et al (2010) Ischemic preconditioning regulates expression of microRNAs and a predicted target, MeCP2, in mouse cortex. J Cereb Blood Flow Metab 30(4):744–756PubMedCrossRefGoogle Scholar
  122. Ma G, Chen S (2004) Diazoxide and N omega-nitro-L-arginine counteracted A beta 1–42-induced cytotoxicity. Neuroreport 15(11):1813–1817PubMedCrossRefGoogle Scholar
  123. Mabuchi T, Kitagawa K et al (2001) Phosphorylation of cAMP response element-binding protein in hippocampal neurons as a protective response after exposure to glutamate in vitro and ischemia in vivo. J Neurosci 21(23):9204–9213PubMedGoogle Scholar
  124. Mandemakers W, Morais VA et al (2007) A cell biological perspective on mitochondrial dysfunction in Parkinson disease and other neurodegenerative diseases. J Cell Sci 120(Pt 10):1707–1716PubMedCrossRefGoogle Scholar
  125. Matsuda N, Sato S et al (2010) PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy. J Cell Biol 189(2):211–221PubMedCrossRefGoogle Scholar
  126. Mattson MP (2007) Calcium and neurodegeneration. Aging Cell 6(3):337–350PubMedCrossRefGoogle Scholar
  127. Matus S, Glimcher LH et al (2011) Protein folding stress in neurodegenerative diseases: a glimpse into the ER. Curr Opin Cell Biol 23(2):239–252PubMedCrossRefGoogle Scholar
  128. Mayanagi K, Gaspar T et al (2007a) Systemic administration of diazoxide induces delayed preconditioning against transient focal cerebral ischemia in rats. Brain Res 1168:106–111PubMedCrossRefGoogle Scholar
  129. Mayanagi K, Gaspar T et al (2007b) The mitochondrial K(ATP) channel opener BMS-191095 reduces neuronal damage after transient focal cerebral ischemia in rats. J Cereb Blood Flow Metab 27(2):348–355PubMedCrossRefGoogle Scholar
  130. McLeod CJ, Pagel I et al (2005) The mitochondrial biogenesis regulatory program in cardiac adaptation to ischemia–a putative target for therapeutic intervention. Trends Cardiovasc Med 15(3):118–123PubMedCrossRefGoogle Scholar
  131. Meller R (2009) The role of the ubiquitin proteasome system in ischemia and ischemic tolerance. Neuroscientist 15(3):243–260PubMedCrossRefGoogle Scholar
  132. Meller R, Minami M et al (2005) CREB-mediated Bcl-2 protein expression after ischemic preconditioning. J Cereb Blood Flow Metab 25(2):234–246PubMedCrossRefGoogle Scholar
  133. Meller R, Cameron JA et al (2006) Rapid degradation of Bim by the ubiquitin-proteasome pathway mediates short-term ischemic tolerance in cultured neurons. J Biol Chem 281(11):7429–7436PubMedCrossRefGoogle Scholar
  134. Meller R, Thompson SJ et al (2008) Ubiquitin proteasome-mediated synaptic reorganization: a novel mechanism underlying rapid ischemic tolerance. J Neurosci 28(1):50–59PubMedCrossRefGoogle Scholar
  135. Michelangeli F, Ogunbayo OA et al (2005) A plethora of interacting organellar Ca2+ stores. Curr Opin Cell Biol 17(2):135–140PubMedCrossRefGoogle Scholar
  136. Mitchell MB, Meng X et al (1995) Preconditioning of isolated rat heart is mediated by protein kinase C. Circ Res 76(1):73–81PubMedCrossRefGoogle Scholar
  137. Morimoto N, Oida Y et al (2007) Involvement of endoplasmic reticulum stress after middle cerebral artery occlusion in mice. Neuroscience 147(4):957–967PubMedCrossRefGoogle Scholar
  138. Mu D, Jiang X et al (2003) Regulation of hypoxia-inducible factor 1alpha and induction of vascular endothelial growth factor in a rat neonatal stroke model. Neurobiol Dis 14(3):524–534PubMedCrossRefGoogle Scholar
  139. Mu D, Chang YS et al (2005) Hypoxia-inducible factor 1alpha and erythropoietin upregulation with deferoxamine salvage after neonatal stroke. Exp Neurol 195(2):407–415PubMedCrossRefGoogle Scholar
  140. Munro S (1998) Localization of proteins to the Golgi apparatus. Trends Cell Biol 8(1):11–15PubMedCrossRefGoogle Scholar
  141. Narendra D, Tanaka A et al (2008) Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol 183(5):795–803PubMedCrossRefGoogle Scholar
  142. Novalija E, Kevin LG et al (2003a) Reactive oxygen species precede the epsilon isoform of protein kinase C in the anesthetic preconditioning signaling cascade. Anesthesiology 99(2):421–428PubMedCrossRefGoogle Scholar
  143. Novalija E, Kevin LG et al (2003b) Anesthetic preconditioning improves adenosine triphosphate synthesis and reduces reactive oxygen species formation in mitochondria after ischemia by a redox dependent mechanism. Anesthesiology 98(5):1155–1163PubMedCrossRefGoogle Scholar
  144. Nurmi A, Lindsberg PJ et al (2004) Nuclear factor-kappaB contributes to infarction after permanent focal ischemia. Stroke 35(4):987–991PubMedCrossRefGoogle Scholar
  145. O’Connor L, Strasser A et al (1998) Bim: a novel member of the Bcl-2 family that promotes apoptosis. EMBO J 17(2):384–395PubMedCrossRefGoogle Scholar
  146. Oddo S (2008) The ubiquitin-proteasome system in Alzheimer’s disease. J Cell Mol Med 12(2):363–373PubMedCrossRefGoogle Scholar
  147. Oida Y, Izuta H et al (2008) Induction of BiP, an ER-resident protein, prevents the neuronal death induced by transient forebrain ischemia in gerbil. Brain Res 1208:217–224PubMedCrossRefGoogle Scholar
  148. Ordonez AN, Jessick VJ et al (2010) Rapid ischemic tolerance induced by adenosine preconditioning results in Bcl-2 interacting mediator of cell death (Bim) degradation by the proteasome. Int J Physiol Pathophysiol Pharmacol 2(1):36–44PubMedGoogle Scholar
  149. Ouyang YB, Xu L et al (2005) Geldanamycin treatment reduces delayed CA1 damage in mouse hippocampal organotypic cultures subjected to oxygen glucose deprivation. Neurosci Lett 380(3):229–233PubMedCrossRefGoogle Scholar
  150. Pain T, Yang XM et al (2000) Opening of mitochondrial K(ATP) channels triggers the preconditioned state by generating free radicals. Circ Res 87(6):460–466PubMedCrossRefGoogle Scholar
  151. Park HK, Chu K et al (2009) Autophagy is involved in the ischemic preconditioning. Neurosci Lett 451(1):16–19PubMedCrossRefGoogle Scholar
  152. Paschen W (2003) Endoplasmic reticulum: a primary target in various acute disorders and degenerative diseases of the brain. Cell Calcium 34(4–5):365–383PubMedCrossRefGoogle Scholar
  153. Paschen W (2004) Endoplasmic reticulum dysfunction in brain pathology: critical role of protein synthesis. Curr Neurovasc Res 1(2):173–181PubMedCrossRefGoogle Scholar
  154. Paschen W, Doutheil J (1999) Disturbances of the functioning of endoplasmic reticulum: a key mechanism underlying neuronal cell injury? J Cereb Blood Flow Metab 19(1):1–18PubMedCrossRefGoogle Scholar
  155. Pavlikova M, Tatarkova Z et al (2009) Alterations induced by ischemic preconditioning on secretory pathways Ca2+ -ATPase (SPCA) gene expression and oxidative damage after global cerebral ischemia/reperfusion in rats. Cell Mol Neurobiol 29(6–7):909–916PubMedCrossRefGoogle Scholar
  156. Peng Z, Ren P et al (2008) Up-regulated HIF-1alpha is involved in the hypoxic tolerance induced by hyperbaric oxygen preconditioning. Brain Res 1212:71–78PubMedCrossRefGoogle Scholar
  157. Pickart CM, Cohen RE (2004) Proteasomes and their kin: proteases in the machine age. Nat Rev Mol Cell Biol 5(3):177–187PubMedCrossRefGoogle Scholar
  158. Ping P, Zhang J et al (1997) Ischemic preconditioning induces selective translocation of protein kinase C isoforms epsilon and eta in the heart of conscious rabbits without subcellular redistribution of total protein kinase C activity. Circ Res 81(3):404–414PubMedCrossRefGoogle Scholar
  159. Pizzo P, Lissandron V et al (2010) The trans-golgi compartment: a new distinct intracellular Ca store. Commun Integr Biol 3(5):462–464PubMedCrossRefGoogle Scholar
  160. Pradillo JM, Romera C et al (2005) TNFR1 upregulation mediates tolerance after brain ischemic preconditioning. J Cereb Blood Flow Metab 25(2):193–203PubMedCrossRefGoogle Scholar
  161. Pradillo JM, Fernandez-Lopez D et al (2009) Toll-like receptor 4 is involved in neuroprotection afforded by ischemic preconditioning. J Neurochem 109(1):287–294PubMedCrossRefGoogle Scholar
  162. Prass K, Scharff A et al (2003) Hypoxia-induced stroke tolerance in the mouse is mediated by erythropoietin. Stroke 34(8):1981–1986PubMedCrossRefGoogle Scholar
  163. Rami A, Bechmann I et al (2008) Exploiting endogenous anti-apoptotic proteins for novel therapeutic strategies in cerebral ischemia. Prog Neurobiol 85(3):273–296PubMedCrossRefGoogle Scholar
  164. Raval AP, Dave KR et al (2007) epsilonPKC phosphorylates the mitochondrial K(+) (ATP) channel during induction of ischemic preconditioning in the rat hippocampus. Brain Res 1184:345–353PubMedCrossRefGoogle Scholar
  165. Ravati A, Ahlemeyer B et al (2001) Preconditioning-induced neuroprotection is mediated by reactive oxygen species and activation of the transcription factor nuclear factor-kappaB. J Neurochem 78(4):909–919PubMedCrossRefGoogle Scholar
  166. Readnower RD, Pandya JD et al (2011) Post-injury administration of the mitochondrial permeability transition pore inhibitor, NIM811, is neuroprotective and improves cognition after traumatic brain injury in rats. J Neurotrauma 28(9):1845–1853PubMedCrossRefGoogle Scholar
  167. Rehni AK, Singh TG et al (2010) Possible involvement of ubiquitin proteasome system and other proteases in acute and delayed aspects of ischemic preconditioning of brain in mice. Biol Pharm Bull 33(12):1953–1957PubMedCrossRefGoogle Scholar
  168. Ritossa F (1996) Discovery of the heat shock response. Cell Stress Chaperones 1(2):97–98PubMedCrossRefGoogle Scholar
  169. Rodriguez-Sinovas A, Boengler K et al (2006) Translocation of connexin 43 to the inner mitochondrial membrane of cardiomyocytes through the heat shock protein 90-dependent TOM pathway and its importance for cardioprotection. Circ Res 99(1):93–101PubMedCrossRefGoogle Scholar
  170. Romera C, Hurtado O et al (2007) Ischemic preconditioning reveals that GLT1/EAAT2 glutamate transporter is a novel PPARgamma target gene involved in neuroprotection. J Cereb Blood Flow Metab 27(7):1327–1338PubMedCrossRefGoogle Scholar
  171. Ron D, Walter P (2007) Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol 8(7):519–529PubMedCrossRefGoogle Scholar
  172. Ruiz-Ramos R, Cebrian ME et al (2005) Benzoquinone activates the ERK/MAPK signaling pathway via ROS production in HL-60 cells. Toxicology 209(3):279–287PubMedCrossRefGoogle Scholar
  173. Runden-Pran E, Haug FM et al (2002) BK channel activity determines the extent of cell degeneration after oxygen and glucose deprivation: a study in organotypical hippocampal slice cultures. Neuroscience 112(2):277–288PubMedCrossRefGoogle Scholar
  174. Ruscher K, Freyer D et al (2002) Erythropoietin is a paracrine mediator of ischemic tolerance in the brain: evidence from an in vitro model. J Neurosci 22(23):10291–10301PubMedGoogle Scholar
  175. Rybnikova E, Gluschenko T et al (2008) Preconditioning induces prolonged expression of transcription factors pCREB and NF-kappa B in the neocortex of rats before and following severe hypobaric hypoxia. J Neurochem 106(3):1450–1458PubMedGoogle Scholar
  176. Sadasivan S, Waghray A et al (2006) Amino acid starvation induced autophagic cell death in PC-12 cells: evidence for activation of caspase-3 but not calpain-1. Apoptosis 11(9):1573–1582PubMedCrossRefGoogle Scholar
  177. Saleh MC, Connell BJ et al (2009) Ischemic tolerance following low dose NMDA involves modulation of cellular stress proteins. Brain Res 1247:212–220PubMedCrossRefGoogle Scholar
  178. Saleh MC, Connell BJ et al (2010) Resveratrol preconditioning induces cellular stress proteins and is mediated via NMDA and estrogen receptors. Neuroscience 166(2):445–454PubMedCrossRefGoogle Scholar
  179. Sato T, Saito T et al (2005) Mitochondrial Ca2+ -activated K+ channels in cardiac myocytes: a mechanism of the cardioprotective effect and modulation by protein kinase A. Circulation 111(2):198–203PubMedCrossRefGoogle Scholar
  180. Saugstad JA (2010) MicroRNAs as effectors of brain function with roles in ischemia and injury, neuroprotection, and neurodegeneration. J Cereb Blood Flow Metab 30(9):1564–1576PubMedCrossRefGoogle Scholar
  181. Scarpulla RC (2006) Nuclear control of respiratory gene expression in mammalian cells. J Cell Biochem 97(4):673–683PubMedCrossRefGoogle Scholar
  182. Schneider A, Martin-Villalba A et al (1999) NF-kappaB is activated and promotes cell death in focal cerebral ischemia. Nat Med 5(5):554–559PubMedCrossRefGoogle Scholar
  183. Semenza GL (2011) Hypoxia-inducible factor 1: regulator of mitochondrial metabolism and mediator of ischemic preconditioning. Biochim Biophys Acta 1813(7):1263–1268PubMedCrossRefGoogle Scholar
  184. Sepulveda MR, Berrocal M et al (2007) Functional and immunocytochemical evidence for the expression and localization of the secretory pathway Ca2+ -ATPase isoform 1 (SPCA1) in cerebellum relative to other Ca2+ pumps. J Neurochem 103(3):1009–1018PubMedCrossRefGoogle Scholar
  185. Sepulveda MR, Marcos D et al (2008) Activity and localization of the secretory pathway Ca2+ -ATPase isoform 1 (SPCA1) in different areas of the mouse brain during postnatal development. Mol Cell Neurosci 38(4):461–473PubMedCrossRefGoogle Scholar
  186. Shao G, Gao CY et al (2005) Alterations of hypoxia-inducible factor-1 alpha in the hippocampus of mice acutely and repeatedly exposed to hypoxia. Neurosignals 14(5):255–261PubMedCrossRefGoogle Scholar
  187. Sheng R, Zhang LS et al (2010) Autophagy activation is associated with neuroprotection in a rat model of focal cerebral ischemic preconditioning. Autophagy 6(4)Google Scholar
  188. Shintani Y, Node K et al (2004) Opening of Ca2+ -activated K+ channels is involved in ischemic preconditioning in canine hearts. J Mol Cell Cardiol 37(6):1213–1218PubMedGoogle Scholar
  189. Sivarajah A, McDonald MC et al (2005) The cardioprotective effects of preconditioning with endotoxin, but not ischemia, are abolished by a peroxisome proliferator-activated receptor-gamma antagonist. J Pharmacol Exp Ther 313(2):896–901PubMedCrossRefGoogle Scholar
  190. Sivaswamy S, Neafsey EJ et al (2010) Neuroprotective preconditioning of rat brain cultures with ethanol: potential transduction by PKC isoforms and focal adhesion kinase upstream of increases in effector heat shock proteins. Eur J Neurosci 32(11):1800–1812PubMedCrossRefGoogle Scholar
  191. Soriano FX, Papadia S et al (2006) Preconditioning doses of NMDA promote neuroprotection by enhancing neuronal excitability. J Neurosci 26(17):4509–4518PubMedCrossRefGoogle Scholar
  192. St-Pierre J, Drori S et al (2006) Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell 127(2):397–408PubMedCrossRefGoogle Scholar
  193. Stenzel-Poore MP, Stevens SL et al (2003) Effect of ischaemic preconditioning on genomic response to cerebral ischaemia: similarity to neuroprotective strategies in hibernation and hypoxia-tolerant states. Lancet 362(9389):1028–1037PubMedCrossRefGoogle Scholar
  194. Stenzel-Poore MP, Stevens SL et al (2004) Genomics of preconditioning. Stroke 35(11 Suppl 1):2683–2686PubMedCrossRefGoogle Scholar
  195. Stenzel-Poore MP, Stevens SL et al (2007) Preconditioning reprograms the response to ischemic injury and primes the emergence of unique endogenous neuroprotective phenotypes: a speculative synthesis. Stroke 38(2 Suppl):680–685PubMedCrossRefGoogle Scholar
  196. Stetler RA, Gao Y et al (2009) HSP27: mechanisms of cellular protection against neuronal injury. Curr Mol Med 9(7):863–872PubMedCrossRefGoogle Scholar
  197. Stetler RA, Gan Y et al (2010) Heat shock proteins: cellular and molecular mechanisms in the central nervous system. Prog Neurobiol 92(2):184–211PubMedCrossRefGoogle Scholar
  198. Sugawara T, Noshita N et al (2001) Neuronal expression of the DNA repair protein Ku 70 after ischemic preconditioning corresponds to tolerance to global cerebral ischemia. Stroke 32(10):2388–2393PubMedCrossRefGoogle Scholar
  199. Sullivan PG, Sebastian AH et al (2011) Therapeutic window analysis of the neuroprotective effects of cyclosporine after traumatic brain injury. J Neurotrauma 28(2):311–318PubMedCrossRefGoogle Scholar
  200. Sun XC, Xian XH et al (2010) Activation of p38 MAPK participates in brain ischemic tolerance induced by limb ischemic preconditioning by up-regulating HSP 70. Exp Neurol 224(2):347–355PubMedCrossRefGoogle Scholar
  201. Tai KK, Truong DD (2002) Activation of adenosine triphosphate-sensitive potassium channels confers protection against rotenone-induced cell death: therapeutic implications for Parkinson’s disease. J Neurosci Res 69(4):559–566PubMedCrossRefGoogle Scholar
  202. Tai KK, McCrossan ZA et al (2003) Activation of mitochondrial ATP-sensitive potassium channels increases cell viability against rotenone-induced cell death. J Neurochem 84(5):1193–1200PubMedCrossRefGoogle Scholar
  203. Tanaka K, Weihrauch D et al (2002) Mechanism of preconditioning by isoflurane in rabbits: a direct role for reactive oxygen species. Anesthesiology 97(6):1485–1490PubMedCrossRefGoogle Scholar
  204. Tang Y, Pacary E et al (2006) Effect of hypoxic preconditioning on brain genomic response before and following ischemia in the adult mouse: identification of potential neuroprotective candidates for stroke. Neurobiol Dis 21(1):18–28PubMedCrossRefGoogle Scholar
  205. Terasaki Y, Sasaki T et al (2010) Activation of NR2A receptors induces ischemic tolerance through CREB signaling. J Cereb Blood Flow Metab 30(8):1441–1449PubMedCrossRefGoogle Scholar
  206. Tong H, Chen W et al (2000) Ischemic preconditioning activates phosphatidylinositol-3-kinase upstream of protein kinase C. Circ Res 87(4):309–315PubMedCrossRefGoogle Scholar
  207. Turturici G, Sconzo G et al (2011) Hsp70 and its molecular role in nervous system diseases. Biochem Res Int 2011:618127PubMedGoogle Scholar
  208. Twig G, Shirihai OS (2011) The interplay between mitochondrial dynamics and mitophagy. Antioxid Redox Signal 14(10):1939–1951PubMedCrossRefGoogle Scholar
  209. Valentim LM, Geyer AB et al (2001) Effects of global cerebral ischemia and preconditioning on heat shock protein 27 immunocontent and phosphorylation in rat hippocampus. Neuroscience 107(1):43–49PubMedCrossRefGoogle Scholar
  210. Valentim LM, Rodnight R et al (2003) Changes in heat shock protein 27 phosphorylation and immunocontent in response to preconditioning to oxygen and glucose deprivation in organotypic hippocampal cultures. Neuroscience 118(2):379–386PubMedCrossRefGoogle Scholar
  211. Vanden Hoek T, Becker LB et al (2000) Preconditioning in cardiomyocytes protects by attenuating oxidant stress at reperfusion. Circ Res 86(5):541–548PubMedCrossRefGoogle Scholar
  212. Wang X, Yin C et al (2004) Opening of Ca2+ -activated K+ channels triggers early and delayed preconditioning against I/R injury independent of NOS in mice. Am J Physiol Heart Circ Physiol 287(5):H2070–H2077PubMedCrossRefGoogle Scholar
  213. Wang RM, Yang F et al (2006) Preconditioning-induced activation of ERK5 is dependent on moderate Ca2+ influx via NMDA receptors and contributes to ischemic tolerance in the hippocampal CA1 region of rats. Life Sci 79(19):1839–1846PubMedCrossRefGoogle Scholar
  214. Wang Q, Tang XN et al (2007a) The inflammatory response in stroke. J Neuroimmunol 184(1–2):53–68PubMedCrossRefGoogle Scholar
  215. Wang X, Hagberg H et al (2007b) Dual role of intrauterine immune challenge on neonatal and adult brain vulnerability to hypoxia-ischemia. J Neuropathol Exp Neurol 66(6):552–561PubMedCrossRefGoogle Scholar
  216. Wang H, Lu S et al (2011) Sevoflurane preconditioning confers neuroprotection via anti-inflammatory effects. Front Biosci (Elite Ed) 3:604–615CrossRefGoogle Scholar
  217. Watanabe M, Katsura K et al (2008) Involvement of mitoKATP channel in protective mechanisms of cerebral ischemic tolerance. Brain Res 1238:199–207PubMedCrossRefGoogle Scholar
  218. Wei H, Xie Z (2009) Anesthesia, calcium homeostasis and Alzheimer’s disease. Curr Alzheimer Res 6(1):30–35PubMedCrossRefGoogle Scholar
  219. White C, Li C et al (2005) The endoplasmic reticulum gateway to apoptosis by Bcl-X(L) modulation of the InsP3R. Nat Cell Biol 7(10):1021–1028PubMedCrossRefGoogle Scholar
  220. Wootton LL, Argent CC et al (2004) The expression, activity and localisation of the secretory pathway Ca2+ -ATPase (SPCA1) in different mammalian tissues. Biochim Biophys Acta 1664(2):189–197PubMedCrossRefGoogle Scholar
  221. Wu X, Qian Z et al (2009) Ginkgolide B preconditioning protects neurons against ischaemia-induced apoptosis. J Cell Mol Med 13(11–12):4474–4483PubMedCrossRefGoogle Scholar
  222. Wu Y, Li X et al (2010) Neuroprotection of deferoxamine on rotenone-induced injury via accumulation of HIF-1 alpha and induction of autophagy in SH-SY5Y cells. Neurochem Int 57(3):198–205PubMedCrossRefGoogle Scholar
  223. Xie J, Duan L et al (2010) K(ATP) channel openers protect mesencephalic neurons against MPP+-induced cytotoxicity via inhibition of ROS production. J Neurosci Res 88(2):428–437PubMedCrossRefGoogle Scholar
  224. Xu W, Liu Y et al (2002) Cytoprotective role of Ca2+-activated K+ channels in the cardiac inner mitochondrial membrane. Science 298(5595):1029–1033PubMedCrossRefGoogle Scholar
  225. Yan W, Zhang H et al (2011) Autophagy activation is involved in neuroprotection induced by hyperbaric oxygen preconditioning against focal cerebral ischemia in rats. Brain Res 1402:109–121PubMedCrossRefGoogle Scholar
  226. Yang Y, Liu X et al (2006) Activation of mitochondrial ATP-sensitive potassium channels improves rotenone-related motor and neurochemical alterations in rats. Int J Neuropsychopharmacol 9(1):51–61PubMedCrossRefGoogle Scholar
  227. Yang HY, Kim J et al (2007) Cross-linking of MHC class II molecules interferes with phorbol 12,13-dibutyrate-induced differentiation of resting B cells by inhibiting Rac-associated ROS-dependent ERK/p38 MAP kinase pathways leading to NF-kappaB activation. Mol Immunol 44(7):1577–1586PubMedCrossRefGoogle Scholar
  228. Yildirim F, Gertz K et al (2008) Inhibition of histone deacetylation protects wildtype but not gelsolin-deficient mice from ischemic brain injury. Exp Neurol 210(2):531–542PubMedCrossRefGoogle Scholar
  229. Yin W, Signore AP et al (2008) Rapidly increased neuronal mitochondrial biogenesis after hypoxic-ischemic brain injury. Stroke 39(11):3057–3063PubMedCrossRefGoogle Scholar
  230. Yu Z, Luo H et al (1999) The endoplasmic reticulum stress-responsive protein GRP78 protects neurons against excitotoxicity and apoptosis: suppression of oxidative stress and stabilization of calcium homeostasis. Exp Neurol 155(2):302–314PubMedCrossRefGoogle Scholar
  231. Zhang HP, Yuan LB et al (2010) Isoflurane preconditioning induces neuroprotection by attenuating ubiquitin-conjugated protein aggregation in a mouse model of transient global cerebral ischemia. Anesth Analg 111(2):506–514PubMedCrossRefGoogle Scholar
  232. Zhao Y, Patzer A et al (2006) Activation of cerebral peroxisome proliferator-activated receptors gamma promotes neuroprotection by attenuation of neuronal cyclooxygenase-2 overexpression after focal cerebral ischemia in rats. FASEB J 20(8):1162–1175PubMedCrossRefGoogle Scholar
  233. Zu L, Zheng X et al (2011) Ischemic preconditioning attenuates mitochondrial localization of PTEN induced by ischemia-reperfusion. Am J Physiol Heart Circ Physiol 300(6):H2177–H2186PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Peiying Li
    • 1
    Email author
  • Rehana Leak
    • 2
  • Yu Gan
    • 1
  • Xiaoming Hu
    • 1
  • R. Anne Stetler
    • 1
  • Jun Chen
    • 1
  1. 1.Department of Neurology and the Center for Cerebrovascular Disease ResearchUniversity of Pittsburgh School of MedicinePittsburghUSA
  2. 2.Division of Pharmaceutical Sciences, Mylan School of PharmacyDuquesne UniversityPittsburghUSA

Personalised recommendations