Skip to main content

Advertisement

SpringerLink
Log in

Structural and functional alterations of cerebellum following fluid percussion injury in rats

  • Research Article
  • Published:
Experimental Brain Research Aims and scope Submit manuscript

Abstract

Cerebellum was shown to be vulnerable to traumatic brain injury (TBI) in experimental animals. However, the detailed pathological and functional changes within the cerebellum following TBI are not known. Using our established cerebellum fluid percussion injury (FPI) model, we characterized the temporal pattern and the nature of structural damage following FPI, as well as the functional changes of Purkinje cells in response to climbing fiber activation. Our results showed that 60% of Purkinje cells died within the first 24 h following moderate FPI. In contrast, clusters of densely stained shrunken granule cells were stained positive for terminal deoxynucleotidyl transferase-mediated UTP nick end labeling (TUNEL) in 1, 3 or 7 days following FPI animals. We also observed an accompanying structural damage to the cerebellar white matter tract. Disconnected axonal fibers appeared 1 day post-FPI, and loss of white matter fibers were visible 3 and 7 days post-FPI. Massive accumulation of β-amyloid precursor protein (βAPP) was found in the white matter tracts and molecular layer in the cerebellum of 1, 3 or 7 days FPI animals. Our functional study showed that the majority of Purkinje cells from 1 day and all cells from 3 to 7 days post-FPI had distorted membrane potential and synaptic responses to climbing fiber activation. These results suggested that there is a co-related structural and functional deterioration with a specific temporal pattern in the cerebellum following FPI. These observations provide a basis for future mechanistic investigations aiming to realize neuroprotection from cerebellar neuronal death and loss of cerebellar functionality.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  • Aarts M, Iihara K, Wei WL, Xiong ZG, Arundine M, Cerwinski W, MacDonald JF, Tymianski M (2003) A key role for TRPM7 channels in anoxic neuronal death. Cell 115:863–877

    PubMed  CAS  Google Scholar 

  • Ai J, Baker A (2002) Presynaptic hyperexcitability at cerebellar synapses in traumatic injury rat. Neurosci Lett 332:155–158

    PubMed  CAS  Google Scholar 

  • Ai J, Baker A (2004) Presynaptic excitability as a potential target for the treatment of the traumatic cerebellum. Pharmacology 71:192–198

    PubMed  CAS  Google Scholar 

  • Airaksinen MS, Eilers J, Garaschuk O, Thoenen H, Konnerth A, Meyer M (1997) Ataxia and altered dendritic calcium signaling in mice carrying a targeted null mutation of the calbindin D28k gene. Proc Natl Acad Sci USA 94:1488–1493

    PubMed  CAS  Google Scholar 

  • Akasu T, Muraoka N, Hasuo H (2002) Hyperexcitability of hippocampal CA1 neurons after fluid percussion injury of the rat cerebral cortex. Neurosci Lett 329:305–308

    PubMed  CAS  Google Scholar 

  • Allen GV, Chase T (2001) Induction of heat shock proteins and motor function deficits after focal cerebellar injury. Neuroscience 102:603–614

    PubMed  CAS  Google Scholar 

  • Baker AJ, Moulton RJ, MacMillan VH, Shedden PM (1993) Excitatory amino acids in cerebrospinal fluid following traumatic brain injury in humans. J Neurosurg 79:369–372

    PubMed  CAS  Google Scholar 

  • Baker AJ, Phan N, Moulton RJ, Fehlings MG, Yucel Y, Zhao M, Liu E, Tian GF (2002) Attenuation of the electrophysiological function of the corpus callosum after fluid percussion injury in the rat. J Neurotrauma 19:587–599

    PubMed  CAS  Google Scholar 

  • Barski JJ, Hartmann J, Rose CR, Hoebeek F, Morl K, Noll-Hussong M, De Zeeuw CI, Konnerth A, Meyer M (2003) Calbindin in cerebellar Purkinje cells is a critical determinant of the precision of motor coordination. J Neurosci 23:3469–3477

    PubMed  CAS  Google Scholar 

  • Brorson JR, Manzolillo PA, Miller RJ (1994) Ca2+ entry via AMPA/KA receptors and excitotoxicity in cultured cerebellar Purkinje cells. J Neurosci 14:187–197

    PubMed  CAS  Google Scholar 

  • Brorson JR, Manzolillo PA, Gibbons SJ, Miller RJ (1995) AMPA receptor desensitization predicts the selective vulnerability of cerebellar Purkinje cells to excitotoxicity. J Neurosci 15:4515–4524

    PubMed  CAS  Google Scholar 

  • Buki A, Okonkwo DO, Povlishock JT (1999) Postinjury cyclosporin A administration limits axonal damage and disconnection in traumatic brain injury. J Neurotrauma 16:511–521

    PubMed  CAS  Google Scholar 

  • Buki A, Farkas O, Doczi T, Povlishock JT (2003) Preinjury administration of the calpain inhibitor MDL-28170 attenuates traumatically induced axonal injury. J Neurotrauma 20:261–268

    PubMed  CAS  Google Scholar 

  • Celio MR (1990) Calbindin D-28k and parvalbumin in the rat nervous system. Neuroscience 35:375–475

    PubMed  CAS  Google Scholar 

  • Choi DW (1992) Excitotoxic cell death. J Neurobiol 23:1261–1276

    PubMed  CAS  Google Scholar 

  • Contestabile A (2002) Cerebellar granule cells as a model to study mechanisms of neuronal apoptosis or survival in vivo and in vitro. Cerebellum 1:41–55

    PubMed  CAS  Google Scholar 

  • Dekkers J, Bayley P, Dick JR, Schwaller B, Berchtold MW, Greensmith L (2004) Over-expression of parvalbumin in transgenic mice rescues motoneurons from injury-induced cell death. Neuroscience 123:459–466

    PubMed  CAS  Google Scholar 

  • Ding Y, Yao B, Lai Q, McAllister JP (2001) Impaired motor learning and diffuse axonal damage in motor and visual systems of the rat following traumatic brain injury. Neurol Res 23:193–202

    PubMed  CAS  Google Scholar 

  • Dixon CE, Lyeth BG, Povlishock JT, Findling RL, Hamm RJ, Marmarou A, Young HF, Hayes RL (1987) A fluid percussion model of experimental brain injury in the rat. J Neurosurg 67:110–119

    PubMed  CAS  Google Scholar 

  • Dore S, Goto S, Sampei K, Blackshaw S, Hester LD, Ingi T, Sawa A, Traystman RJ, Koehler RC, Snyder SH (2000) Heme oxygenase-2 acts to prevent neuronal death in brain cultures and following transient cerebral ischemia. Neuroscience 99:587–592

    PubMed  CAS  Google Scholar 

  • D’Orlando C, Fellay B, Schwaller B, Salicio V, Bloc A, Gotzos V, Celio MR (2001) Calretinin and calbindin D-28k delay the onset of cell death after excitotoxic stimulation in transfected P19 cells. Brain Res 909:145–158

    PubMed  CAS  Google Scholar 

  • D’Orlando C, Celio MR, Schwaller B (2002) Calretinin and calbindin D-28k, but not parvalbumin protect against glutamate-induced delayed excitotoxicity in transfected N18–RE 105 neuroblastoma–retina hybrid cells. Brain Res 945:181–190

    PubMed  CAS  Google Scholar 

  • Ferrer I, Pozas E, Marti M, Blanco R, Planas AM (1997) Methylazoxymethanol acetate-induced apoptosis in the external granule cell layer of the developing cerebellum of the rat is associated with strong c-Jun expression and formation of high molecular weight c-Jun complexes. J Neuropathol Exp Neurol 56:1–9

    Article  PubMed  CAS  Google Scholar 

  • Finnie JW, Blumbergs PC, Manavis J (1999) Multifocal cerebellar granular layer necrosis in traumatically head-injured lambs. Vet Pathol 36:256–258

    PubMed  CAS  Google Scholar 

  • Floyd CL, Golden KM, Black RT, Hamm RJ, Lyeth BG (2002) Craniectomy position affects morris water maze performance and hippocampal cell loss after parasagittal fluid percussion. J Neurotrauma 19:303–316

    PubMed  Google Scholar 

  • Fonnum F, Lock EA (2000) Cerebellum as a target for toxic substances. Toxicol Lett 112–113:9–16

    PubMed  Google Scholar 

  • Fukuda K, Aihara N, Sagar SM, Sharp FR, Pitts LH, Honkaniemi J, Noble LJ (1996) Purkinje cell vulnerability to mild traumatic brain injury. J Neurotrauma 13:255–266

    Article  PubMed  CAS  Google Scholar 

  • Gary DS, Sooy K, Chan SL, Christakos S, Mattson MP (2000) Concentration- and cell type-specific effects of calbindin D28k on vulnerability of hippocampal neurons to seizure-induced injury. Brain Res Mol Brain Res 75:89–95

    PubMed  CAS  Google Scholar 

  • Gentleman SM, Nash MJ, Sweeting CJ, Graham DI, Roberts GW (1993) Beta-amyloid precursor protein (beta APP) as a marker for axonal injury after head injury. Neurosci Lett 160:139–144

    PubMed  CAS  Google Scholar 

  • Gilman S (1994) Cerebellar control of movement. Ann Neurol 35:3–4

    PubMed  CAS  Google Scholar 

  • Gochuico BR, Williams MC, Fine A (1997) Simultaneous in situ hybridization and TUNEL to identify cells undergoing apoptosis. Histochem J 29:413–418

    PubMed  CAS  Google Scholar 

  • Gorrie C, Oakes S, Duflou J, Blumbergs P, Waite PM (2002) Axonal injury in children after motor vehicle crashes: extent, distribution, and size of axonal swellings using beta-APP immunohistochemistry. J Neurotrauma 19:1171–1182

    PubMed  Google Scholar 

  • Hallam TM, Floyd CL, Folkerts MM, Lee LL, Gong QZ, Lyeth BG, Muizelaar JP, Berman RF (2004) Comparison of behavioral deficits and acute neuronal degeneration in rat lateral fluid percussion and weight-drop brain injury models. J Neurotrauma 21:521–539

    PubMed  Google Scholar 

  • Hoshino S, Kobayashi S, Furukawa T, Asakura T, Teramoto A (2003) Multiple immunostaining methods to detect traumatic axonal injury in the rat fluid-percussion brain injury model. Neurol Med Chir (Tokyo) 43:165–173

    Google Scholar 

  • Iacopino A, Christakos S, German D, Sonsalla PK, Altar CA (1992) Calbindin-D28K-containing neurons in animal models of neurodegeneration: possible protection from excitotoxicity. Brain Res Mol Brain Res 13:251–261

    PubMed  CAS  Google Scholar 

  • Ito M (1987) Signal processing in cerebellar Purkinje cells. Physiol Bohemoslov 36:203–216

    PubMed  CAS  Google Scholar 

  • Ito M (2001) Cerebellar long-term depression: characterization, signal transduction, and functional roles. Physiol Rev 81:1143–1195

    PubMed  CAS  Google Scholar 

  • Koizumi H, Povlishock JT (1998) Posttraumatic hypothermia in the treatment of axonal damage in an animal model of traumatic axonal injury. J Neurosurg 89:303–309

    Article  PubMed  CAS  Google Scholar 

  • Labat-Moleur F, Guillermet C, Lorimier P, Robert C, Lantuejoul S, Brambilla E, Negoescu A (1998) TUNEL apoptotic cell detection in tissue sections: critical evaluation and improvement critical evaluation and improvement. J Histochem Cytochem 46:327–334

    PubMed  CAS  Google Scholar 

  • Lalonde R, Strazielle C (2003) The effects of cerebellar damage on maze learning in animals. Cerebellum 2:300–309

    PubMed  CAS  Google Scholar 

  • Lambri M, Djurovic V, Kibble M, Cairns N, Al Sarraj S (2001) Specificity and sensitivity of betaAPP in head injury. Clin Neuropathol 20:263–271

    PubMed  CAS  Google Scholar 

  • Laurer HL, McIntosh TK (2001) Pharmacologic therapy in traumatic brain injury: update on experimental treatment strategies. Curr Pharm Des 7:1505–1516

    PubMed  CAS  Google Scholar 

  • Leiner HC, Leiner AL, Dow RS (1991) The human cerebro-cerebellar system: its computing, cognitive, and language skills. Behav Brain Res 44:113–128

    PubMed  CAS  Google Scholar 

  • Leiner HC, Leiner AC, Dow RS (1993) Cognitive and language functions of the human cerebellum. Trends Neurosci 16:444–447

    PubMed  CAS  Google Scholar 

  • Lewis SB, Finnie JW, Blumbergs PC, Scott G, Manavis J, Brown C, Reilly PL, Jones NR, McLean AJ (1996) A head impact model of early axonal injury in the sheep. J Neurotrauma 13:505–514

    PubMed  CAS  Google Scholar 

  • Llinas R, Welsh JP (1993) On the cerebellum and motor learning. Curr Opin Neurobiol 3:958–965

    PubMed  CAS  Google Scholar 

  • Llinas R, Lang EJ, Welsh JP (1997) The cerebellum, LTD, and memory: alternative views. Learn Mem 3:445–455

    PubMed  CAS  Google Scholar 

  • Lossi L, Zagzag D, Greco MA, Merighi A (1998) Apoptosis of undifferentiated progenitors and granule cell precursors in the postnatal human cerebellar cortex correlates with expression of BCL-2, ICE, and CPP32 proteins. J Comp Neurol 399:359–372

    PubMed  CAS  Google Scholar 

  • Lossi L, Mioletti S, Merighi A (2002) Synapse-independent and synapse-dependent apoptosis of cerebellar granule cells in postnatal rabbits occur at two subsequent but partly overlapping developmental stages. Neuroscience 112:509–523

    PubMed  CAS  Google Scholar 

  • Lukas W, Jones KA (1994) Cortical neurons containing calretinin are selectively resistant to calcium overload and excitotoxicity in vitro. Neuroscience 61:307–316

    PubMed  CAS  Google Scholar 

  • Lynch DR, Dawson TM (1994) Secondary mechanisms in neuronal trauma. Curr Opin Neurol 7:510–516

    PubMed  CAS  Google Scholar 

  • Maas AI (2001) Neuroprotective agents in traumatic brain injury. Expert Opin Investig Drugs 10:753–767

    PubMed  CAS  Google Scholar 

  • Maas AI, Dearden M, Servadei F, Stocchetti N, Unterberg A (2000) Current recommendations for neurotrauma. Curr Opin Crit Care 6:281–292

    PubMed  Google Scholar 

  • Machado SG, Murray GD, Teasdale GM (1999) Evaluation of designs for clinical trials of neuroprotective agents in head injury. European Brain Injury Consortium. J Neurotrauma 16:1131–1138

    PubMed  CAS  Google Scholar 

  • Marshall LF (2000a) Epidemiology and cost of central nervous system injury. Clin Neurosurg 46:105–112

    CAS  Google Scholar 

  • Marshall LF (2000b) Head injury: recent past, present, and future. Neurosurgery 47:546–561

    CAS  Google Scholar 

  • Martin LJ, Sieber FE, Traystman RJ (2000) Apoptosis and necrosis occur in separate neuronal populations in hippocampus and cerebellum after ischemia and are associated with differential alterations in metabotropic glutamate receptor signaling pathways. J Cereb Blood Flow Metab 20:153–167

    PubMed  CAS  Google Scholar 

  • Maschke M, Dietrich U, Timmann-Braun D (2002) Posterior fossa trauma. In: Manto MU, Pandolfo M (eds) The cerebellum and its disorders. Cambridge University Press, Cambridge, pp 288–304

    Google Scholar 

  • Matthews MA, Carey ME, Soblosky JS, Davidson JF, Tabor SL (1998) Focal brain injury and its effects on cerebral mantle, neurons, and fiber tracts. Brain Res 794:1–18

    PubMed  CAS  Google Scholar 

  • Mattson MP, Cheng B, Baldwin SA, Smith-Swintosky VL, Keller J, Geddes JW, Scheff SW, Christakos S (1995) Brain injury and tumor necrosis factors induce calbindin D-28k in astrocytes: evidence for a cytoprotective response. J Neurosci Res 42:357–370

    PubMed  CAS  Google Scholar 

  • Mautes AE, Fukuda K, Noble LJ (1996) Cellular response in the cerebellum after midline traumatic brain injury in the rat. Neurosci Lett 214:95–98

    PubMed  CAS  Google Scholar 

  • McIntosh TK, Noble L, Andrews B, Faden AI (1987) Traumatic brain injury in the rat: characterization of a midline fluid–percussion model. Cent Nerv Syst Trauma 4:119–134

    PubMed  CAS  Google Scholar 

  • Migheli A, Attanasio A, Lee WH, Bayer SA, Ghetti B (1995) Detection of apoptosis in weaver cerebellum by electron microscopic in situ end-labeling of fragmented DNA. Neurosci Lett 199:53–56

    PubMed  CAS  Google Scholar 

  • Mouginot D, Gahwiler BH (1995) Characterization of synaptic connections between cortex and deep nuclei of the rat cerebellum in vitro. Neuroscience 64:699–712

    PubMed  CAS  Google Scholar 

  • Murray CJ, Lopez AD (1997) Alternative projections of mortality and disability by cause 1990–2020: global burden of disease study. Lancet 349:1498–1504

    PubMed  CAS  Google Scholar 

  • Mysiw WJ, Corrigan JD, Gribble MW (1990) The ataxic subgroup: a discrete outcome after traumatic brain injury. Brain Inj 4:247–255

    PubMed  CAS  Google Scholar 

  • Narayan RK, Michel ME, Ansell B, Baethmann A, Biegon A, Bracken MB, Bullock MR, Choi SC, Clifton GL, Contant CF, Coplin WM, Dietrich WD, Ghajar J, Grady SM, Grossman RG, Hall ED, Heetderks W, Hovda DA, Jallo J, Katz RL, Knoller N, Kochanek PM, Maas AI, Majde J, Marion DW, Marmarou A, Marshall LF, McIntosh TK, Miller E, Mohberg N, Muizelaar JP, Pitts LH, Quinn P, Riesenfeld G, Robertson CS, Strauss KI, Teasdale G, Temkin N, Tuma R, Wade C, Walker MD, Weinrich M, Whyte J, Wilberger J, Young AB, Yurkewicz L (2002) Clinical trials in head injury. J Neurotrauma 19:503–557

    PubMed  Google Scholar 

  • Nonaka S, Katsube N, Chuang DM (1998) Lithium protects rat cerebellar granule cells against apoptosis induced by anticonvulsants, phenytoin and carbamazepine. J Pharmacol Exp Ther 286:539–547

    PubMed  CAS  Google Scholar 

  • Oberto A, Marks N, Evans HL, Guidotti A (1996) Lead (Pb+2) promotes apoptosis in newborn rat cerebellar neurons: pathological implications. J Pharmacol Exp Ther 279:435–442

    PubMed  CAS  Google Scholar 

  • Ogura H, Yasuda M, Nakamura S, Yamashita H, Mikoshiba K, Ohmori H (2002) Neurotoxic damage of granule cells in the dentate gyrus and the cerebellum and cognitive deficit following neonatal administration of phenytoin in mice. J Neuropathol Exp Neurol 61:956–967

    PubMed  CAS  Google Scholar 

  • O’Hearn E, Molliver ME (1997) The olivocerebellar projection mediates ibogaine-induced degeneration of Purkinje cells: a model of indirect, trans-synaptic excitotoxicity. J Neurosci 17:8828–8841

    PubMed  CAS  Google Scholar 

  • Ohgoh M, Yamazaki K, Ogura H, Nishizawa Y, Tanaka I (2000) Apoptotic cell death of cerebellar granule neurons in genetically ataxia (ax) mice. Neurosci Lett 288:167–170

    PubMed  CAS  Google Scholar 

  • Otsuka N, Tomonaga M, Ikeda K (1991) Rapid appearance of beta-amyloid precursor protein immunoreactivity in damaged axons and reactive glial cells in rat brain following needle stab injury. Brain Res 568:335–338

    PubMed  CAS  Google Scholar 

  • Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates, Fourth edn. Academic Press, London

    Google Scholar 

  • Peng J, Wu Z, Wu Y, Hsu M, Stevenson FF, Boonplueang R, Roffler-Tarlov SK, Andersen JK (2002) Inhibition of caspases protects cerebellar granule cells of the weaver mouse from apoptosis and improves behavioral phenotype. J Biol Chem 277:44285–44291

    PubMed  CAS  Google Scholar 

  • Rao JK, Letada P, Haverstick DM, Herman MM, Savory J (1998) Modifications to the in situ TUNEL method for detection of apoptosis in paraffin-embedded tissue sections. Ann Clin Lab Sci 28:131–137

    PubMed  CAS  Google Scholar 

  • Runnerstam M, Bao F, Huang Y, Shi J, Gutierrez E, Hamberger A, Hansson HA, Viano D, Haglid K (2001) A new model for diffuse brain injury by rotational acceleration: II. Effects on extracellular glutamate, intracranial pressure, and neuronal apoptosis. J Neurotrauma 18:259–273

    PubMed  CAS  Google Scholar 

  • Santhakumar V, Bender R, Frotscher M, Ross ST, Hollrigel GS, Toth Z, Soltesz I (2000) Granule cell hyperexcitability in the early post-traumatic rat dentate gyrus: the ‘irritable mossy cell’ hypothesis. J Physiol 524(Pt 1):117–134

    PubMed  CAS  Google Scholar 

  • Santhakumar V, Ratzliff AD, Jeng J, Toth Z, Soltesz I (2001) Long-term hyperexcitability in the hippocampus after experimental head trauma. Ann Neurol 50:708–717

    PubMed  CAS  Google Scholar 

  • Sastry BR, Morishita W, Yip S, Shew T (1997) GABA-ergic transmission in deep cerebellar nuclei. Prog Neurobiol 53:259–271

    PubMed  CAS  Google Scholar 

  • Sattler R, Tymianski M (2000) Molecular mechanisms of calcium-dependent excitotoxicity. J Mol Med 78:3–13

    PubMed  CAS  Google Scholar 

  • Sattler R, Tymianski M (2001) Molecular mechanisms of glutamate receptor-mediated excitotoxic neuronal cell death. Mol Neurobiol 24:107–129

    PubMed  CAS  Google Scholar 

  • Schmahmann JD (1991) An emerging concept. The cerebellar contribution to higher function. Arch Neurol 48:1178–1187

    PubMed  CAS  Google Scholar 

  • Schmolesky MT, Weber JT, De Zeeuw CI, Hansel C (2002) The making of a complex spike: ionic composition and plasticity. Ann N Y Acad Sci 978:359–390

    PubMed  Google Scholar 

  • Schwaller B, Meyer M, Schiffmann S (2002) ‘New’ functions for ‘old’ proteins: the role of the calcium-binding proteins calbindin D-28k, calretinin and parvalbumin, in cerebellar physiology. Studies with knockout mice. Cerebellum 1:241–258

    PubMed  CAS  Google Scholar 

  • Scotti AL (1995) Calbindin D28k in the olivocerebellar projection A light and electron microscope study. J Anat 187(Pt 3):649–659

    PubMed  CAS  Google Scholar 

  • Segal JA, Skolnick P (2000) Spermine-induced toxicity in cerebellar granule neurons is independent of its actions at NMDA receptors. J Neurochem 74:60–69

    PubMed  CAS  Google Scholar 

  • Selimi F, Doughty M, Delhaye-Bouchaud N, Mariani J (2000) Target-related and intrinsic neuronal death in Lurcher mutant mice are both mediated by caspase-3 activation. J Neurosci 20:992–1000

    PubMed  CAS  Google Scholar 

  • Shang T, Kotamraju S, Kalivendi SV, Hillard CJ, Kalyanaraman B (2004) 1-Methyl-4-phenylpyridinium-induced apoptosis in cerebellar granule neurons is mediated by transferrin receptor iron-dependent depletion of tetrahydrobiopterin and neuronal nitric-oxide synthase-derived superoxide. J Biol Chem 279:19099–19112

    PubMed  CAS  Google Scholar 

  • Sherriff FE, Bridges LR, Gentleman SM, Sivaloganathan S, Wilson S (1994) Markers of axonal injury in post mortem human brain. Acta Neuropathol (Berl) 88:433–439

    CAS  Google Scholar 

  • Singh R, Upadhyay G, Kumar S, Kapoor A, Kumar A, Tiwari M, Godbole MM (2003) Hypothyroidism alters the expression of Bcl-2 family genes to induce enhanced apoptosis in the developing cerebellum. J Endocrinol 176:39–46

    PubMed  CAS  Google Scholar 

  • Singleton RH, Stone JR, Okonkwo DO, Pellicane AJ, Povlishock JT (2001) The immunophilin ligand FK506 attenuates axonal injury in an impact-acceleration model of traumatic brain injury. J Neurotrauma 18:607–614

    PubMed  CAS  Google Scholar 

  • Slemmer JE, Weber JT, De Zeeuw CI (2004) Cell death, glial protein alterations and elevated S-100 beta release in cerebellar cell cultures following mechanically induced trauma. Neurobiol Dis 15:563–572

    PubMed  CAS  Google Scholar 

  • Sosin DM, Sniezek JE, Thurman DJ (1996) Incidence of mild and moderate brain injury in the United States, 1991. Brain Inj 10:47–54

    PubMed  CAS  Google Scholar 

  • Soto-Ares G, Vinchon M, Delmaire C, Abecidan E, Dhellemes P, Pruvo JP (2001) Cerebellar atrophy after severe traumatic head injury in children. Childs Nerv Syst 17:263–269

    PubMed  CAS  Google Scholar 

  • Stone JR, Singleton RH, Povlishock JT (2000) Antibodies to the C-terminus of the beta-amyloid precursor protein (APP): a site specific marker for the detection of traumatic axonal injury. Brain Res 871:288–302

    PubMed  CAS  Google Scholar 

  • Strahlendorf JC, Brandon T, Miles R, Strahlendorf HK (1998) AMPA receptor-mediated alterations of intracellular calcium homeostasis in rat cerebellar Purkinje cells in vitro: correlates to dark cell degeneration. Neurochem Res 23:1355–1362

    PubMed  CAS  Google Scholar 

  • Suh YS, Oda S, Kang YH, Kim H, Rhyu IJ (2002) Apoptotic cell death of cerebellar granule cells in rolling mouse Nagoya. Neurosci Lett 325:1–4

    PubMed  CAS  Google Scholar 

  • de Talamoni N, Smith CA, Wasserman RH, Beltramino C, Fullmer CS, Penniston JT (1993) Immunocytochemical localization of the plasma membrane calcium pump, calbindin-D28k, and parvalbumin in Purkinje cells of avian and mammalian cerebellum. Proc Natl Acad Sci USA 90:11949–11953

    PubMed  Google Scholar 

  • Tang YP, Noda Y, Hasegawa T, Nabeshima T (1997) A concussive-like brain injury model in mice (I): impairment in learning and memory. J Neurotrauma 14:851–862

    PubMed  CAS  Google Scholar 

  • de Torres C, Munell F, Ferrer I, Reventos J, Macaya A. (1997) Identification of necrotic cell death by the TUNEL assay in the hypoxic-ischemic neonatal rat brain. Neurosci Lett 230:1–4

    PubMed  Google Scholar 

  • Tavalin SJ, Ellis EF, Satin LS (1995) Mechanical perturbation of cultured cortical neurons reveals a stretch-induced delayed depolarization. J Neurophysiol 74:2767–2773

    PubMed  CAS  Google Scholar 

  • Tavalin SJ, Ellis EF, Satin LS (1997) Inhibition of the electrogenic Na pump underlies delayed depolarization of cortical neurons after mechanical injury or glutamate. J Neurophysiol 77:632–638

    PubMed  CAS  Google Scholar 

  • Thach WT (1998) A role for the cerebellum in learning movement coordination. Neurobiol Learn Mem 70:177–188

    PubMed  CAS  Google Scholar 

  • Tsai FY, Teal JS, Itabashi HH, Huprich JE, Hieshima GB, Segall HD (1980) Computed tomography of posterior fossa trauma. J Comput Assist Tomogr 4:291–305

    PubMed  CAS  Google Scholar 

  • Watson A, Eilers A, Lallemand D, Kyriakis J, Rubin LL, Ham J (1998) Phosphorylation of c-Jun is necessary for apoptosis induced by survival signal withdrawal in cerebellar granule neurons. J Neurosci 18:751–762

    PubMed  CAS  Google Scholar 

  • Weber JT, De Zeeuw CI, Linden DJ, Hansel C (2003) Long-term depression of climbing fiber-evoked calcium transients in Purkinje cell dendrites. Proc Natl Acad Sci USA 100:2878–2883

    PubMed  CAS  Google Scholar 

  • Wullner U, Loschmann PA, Weller M, Klockgether T (1995) Apoptotic cell death in the cerebellum of mutant weaver and lurcher mice. Neurosci Lett 200:109–112

    PubMed  CAS  Google Scholar 

  • Xiong ZG, Zhu XM, Chu XP, Minami M, Hey J, Wei WL, MacDonald JF, Wemmie JA, Price MP, Welsh MJ, Simon RP (2004) Neuroprotection in ischemia: blocking calcium-permeable acid-sensing ion channels. Cell 118:687–698

    PubMed  CAS  Google Scholar 

  • Yan GM, Irwin RP, Lin SZ, Weller M, Wood KA, Paul SM (1995) Diphenylhydantoin induces apoptotic cell death of cultured rat cerebellar granule neurons. J Pharmacol Exp Ther 274:983–990

    PubMed  CAS  Google Scholar 

  • Yue X, Mehmet H, Penrice J, Cooper C, Cady E, Wyatt JS, Reynolds EO, Edwards AD, Squier MV (1997) Apoptosis and necrosis in the newborn piglet brain following transient cerebral hypoxia–ischaemia. Neuropathol Appl Neurobiol 23:16–25

    PubMed  CAS  Google Scholar 

Download references

Acknowledgment

We would like to acknowledge the financial support from the Great-West Life and London Life Assurance Company. We thank Dr. John T. Weber and Christian Hansel for advice on patch clamp techniques on Purkinje cells from brain slices. We are also very grateful to Ms. Trogadis for helping and using of confocal imaging microscope and Mr. Paul Doherty for his professional proof reading of our manuscript.

Author information

Authors and Affiliations

  1. Traumatic Brain Injury Laboratory, Cara Phelan Centre for Trauma Research, St. Michael’s Hospital, University of Toronto, Toronto, ON, Canada, M5B 1W8

    Jinglu Ai, Elaine Liu, Eugene Park & Andrew J. Baker

Authors
  1. Jinglu Ai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elaine Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eugene Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Andrew J. Baker
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jinglu Ai.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ai, J., Liu, E., Park, E. et al. Structural and functional alterations of cerebellum following fluid percussion injury in rats. Exp Brain Res 177, 95–112 (2007). https://doi.org/10.1007/s00221-006-0654-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00221-006-0654-9

Keywords

Search

Navigation