Advertisement

NeuroRX

, Volume 2, Issue 3, pp 410–422 | Cite as

Animal models of head trauma

  • Ibolja Cernak
Article

Summary

Animal models of traumatic brain injury (TBI) are used to elucidate primary and secondary sequelae underlying human head injury in an effort to identify potential neuroprotective therapies for developing and adult brains. The choice of experimental model depends upon both the research goal and underlying objectives. The intrinsic ability to study injury-induced changes in behavior, physiology, metabolism, the blood/tissue interface, the blood brain barrier, and/or inflammatory- and immune-mediated responses, makes in vivo TBI models essential for neurotrauma research. Whereas human TBI is a highly complex multifactorial disorder, animal trauma models tend to replicate only single factors involved in the pathobiology of head injury using genetically well-defined inbred animals of a single sex. Although such an experimental approach is helpful to delineate key injury mechanisms, the simplicity and hence inability of animal models to reflect the complexity of clinical head injury may underlie the discrepancy between preclinical and clinical trials of neuroprotective therapeutics. Thus, a search continues for new animal models, which would more closely mimic the highly heterogeneous nature of human TBI, and address key factors in treatment optimization.

Key Words

Traumatic brain injury models in vivo neuronal cell death outcome 

References

  1. 1.
    Reilly PL. Brain injury: the pathophysiology of the first hours. “Talk and Die revisited.” J Clin Neurosci 8: 398–403, 2001.PubMedGoogle Scholar
  2. 2.
    Lighthall JW, Anderson TE. In: The neurobiology of cenral nervous system trauma (Salzman SK, Faden AI, eds), pp 3–12. New York/Oxford: Oxford University Press, 1994.Google Scholar
  3. 3.
    Adams JH, Doyle D, Ford I, Gennarelli TA, Graham DI, McLellan DR. Diffuse axonal injury in head injury: definition, diagnosis and grading. Histopathology 15: 49–59, 1989.PubMedGoogle Scholar
  4. 4.
    McIntosh TK, Smith DH, Meaney DF, Kotapka MJ, Gennarelli TA, Graham DI. Neuropathological sequelae of traumatic brain injury: relationship to neurochemical and biomechanical mechanisms. Lab Invest 74: 315–342, 1996.PubMedGoogle Scholar
  5. 5.
    DeKosky ST, Kochanek PM, Clark RS, Ciallella JR, Dixon CE. Secondary injury after head trauma: subacute and long-term mechanisms. Semin Clin Neuropsychiatry 3: 176–185, 1998.PubMedGoogle Scholar
  6. 6.
    Denny-Brown D, Russell WR. Experimental cerebral consussion. Brain 64: 93–164, 1941.Google Scholar
  7. 7.
    Ommaya AK, Gennarelli TA. Cerebral concussion and traumatic unconsciousness. Correlation of experimental and clinical observations of blunt head injuries. Brain 97: 633–654, 1974.PubMedGoogle Scholar
  8. 8.
    Clark RS, Schiding JK, Kaczorowski SL, Marion DW, Kochanek PM. Neutrophil accumulation after traumatic brain injury in rats: comparison of weight drop and controlled cortical impact models. J Neurotrauma 11: 499–506, 1994.PubMedGoogle Scholar
  9. 9.
    Rall JM, Matzilevich DA, Dash PK. Comparative analysis of mRNA levels in the frontal cortex and the hippocampus in the basal state and in response to experimental brain injury. Neuropathol Appl Neurobiol 29: 118–131, 2003.PubMedGoogle Scholar
  10. 10.
    Cenci MA, Whishaw IQ, Schallert T. Animal models of neurological deficits: how relevant is the rat? Nat Rev Neurosci 3: 574–579, 2002.PubMedGoogle Scholar
  11. 11.
    Povlishock JT, Hayes RL, Michel ME, McIntosh TK. Workshop on animal models of traumatic brain injury. J Neurotrauma 11: 723–732, 1994.PubMedGoogle Scholar
  12. 12.
    Gennarelli TA. Animate models of human head injury. J Neurotrauma 11: 357–368, 1994.PubMedGoogle Scholar
  13. 13.
    Ommaya AK, Goldsmith W, Thibault L. Biomechanics and neuropathology of adult and paediatric head injury. Br J Neurosurg 16: 220–242, 2002.PubMedGoogle Scholar
  14. 14.
    Ommaya AK. Head injury mechanisms and the concept of preventive management: a review and critical synthesis. J Neurotrauma 12: 527–546, 1995.PubMedGoogle Scholar
  15. 15.
    David S, Aguayo AJ. Axonal regeneration after crush injury of rat central nervous system fibres innervating peripheral nerve grafts. J Neurocytol 14: 1–12, 1985.PubMedGoogle Scholar
  16. 16.
    Park HJ, Kim HN, Kim KM. Redistribution of facial nerve motor neurons after recovery from nerve crushing injury in the gerbil. Acta Otolaryngol 115: 273–275, 1995.PubMedGoogle Scholar
  17. 17.
    Erb DE, Povlishock JT. Axonal damage in severe traumatic brain injury: an experimental study in cat. Acta Neuropathol (Berl) 76: 347–358, 1988.Google Scholar
  18. 18.
    Conti AC, Raghupathi R, Trojanowski JQ, McIntosh TK. Experimental brain injury induces regionally distinct apoptosis during the acute and delayed post-traumatic period. J Neurosci 18: 5663–5672, 1998.PubMedGoogle Scholar
  19. 19.
    Albensi BC, Knoblach SM, Chew BG, O’Reilly MP, Faden AI, Pekar JJ. Diffusion and high resolution MRI of traumatic brain injury in rats: time course and correlation with histology. Exp Neurol 162: 61–72, 2000.PubMedGoogle Scholar
  20. 20.
    McIntosh TK, Yu T, Gennarelli TA. Alterations in regional brain catecholamine concentrations after experimental brain injury in the rat. J Neurochem 63: 1426–1433, 1994.PubMedGoogle Scholar
  21. 21.
    Faden AI, Demediuk P, Panter SS, Vink R. The role of excitatory amino acids and NMDA receptors in traumatic brain injury. Science 244: 798–800, 1989.PubMedGoogle Scholar
  22. 22.
    Faden AI, Knoblach SM, Cernak I, Fan L, Vink R, Araldi GL, et al. Novel diketopiperazine enhances motor and cognitive recovery after traumatic brain injury in rats and shows neuroprotection in vitro and in vivo. J Cereb Blood Flow Metab 23: 342–354, 2003.PubMedGoogle Scholar
  23. 23.
    Dixon CE, Lighthall JW, Anderson TE. Physiologic, histopathologic, and cineradiographic characterization of a new fluid-percussion model of experimental brain injury in the rat. J Neurotrauma 5: 91–104, 1988.PubMedGoogle Scholar
  24. 24.
    Perri BR, Smith DH, Murai H, Sinson G, Saatman KE, Raghupathi R, et al. Metabolic quantification of lesion volume following experimental traumatic brain injury in the rat. J Neurotrauma 14: 15–22, 1997.PubMedGoogle Scholar
  25. 25.
    Carbonell WS, Maris DO, McCall T, Grady MS. Adaptation of the fluid percussion injury model to the mouse. J Neurotrauma 15: 217–229, 1998.PubMedGoogle Scholar
  26. 26.
    Carbonell WS, Grady MS. Regional and temporal characterization of neuronal, glial, and axonal response after traumatic brain injury in the mouse. Acta Neuropathol (Berl) 98: 396–406, 1999.Google Scholar
  27. 27.
    Sullivan HG, Martinez J, Becker DP, Miller JD, Griffith R, Wist AO. Fluid-percussion model of mechanical brain injury in the cat. J Neurosurg 45: 521–534, 1976.PubMedGoogle Scholar
  28. 28.
    Zauner A, Clausen T, Alves OL, Rice A, Levasseur J, Young HF, et al. Cerebral metabolism after fluid-percussion injury and hypoxia in a feline model. J Neurosurg 97: 643–649, 2002.PubMedGoogle Scholar
  29. 29.
    Pfenninger EG, Reith A, Breitig D, Grunert A, Ahnefeld FW. Early changes of intracranial pressure, perfusion pressure, and blood flow after acute head injury. Part 1: an experimental study of the underlying pathophysiology. J Neurosurg 70: 774–779, 1989.PubMedGoogle Scholar
  30. 30.
    Gibson JB, Maxwell RA, Schweitzer JB, Fabian TC, Proctor KG. Resuscitation from severe hemorrhagic shock after traumatic brain injury using saline, shed blood, or a blood substitute. Shock 17: 234–244, 2002.PubMedGoogle Scholar
  31. 31.
    Haiti R, Medary M, Ruge M, Arfors KE, Ghajar J. Blood-brain barrier breakdown occurs early after traumatic brain injury and is not related to white blood cell adherence. Acta Neurochir Suppl (Wien) 70: 240–242, 1997.Google Scholar
  32. 32.
    Millen JE, Glauser FL, Fairman RP. A comparison of physiological responses to percussive brain trauma in dogs and sheep. J Neurosurg 62: 587–591, 1985.PubMedGoogle Scholar
  33. 33.
    McIntosh TK, Noble L, Andrews B, Faden AI. Traumatic brain injury in the rat: characterization of a midline fluid-percussion model. Cent Nerv Syst Trauma 4: 119–134, 1987.PubMedGoogle Scholar
  34. 34.
    Schmidt RH, Grady MS. Regional patterns of blood-brain barrier breakdown following central and lateral fluid percussion injury in rodents. J Neurotrauma 10: 415–430, 1993.PubMedGoogle Scholar
  35. 35.
    McIntosh TK, Vink R, Noble L, Yamakami I, Femyak S, Soares H, et al. Traumatic brain injury in the rat: characterization of a lateral fluid-percussion model. Neuroscience 28: 233–244, 1989.PubMedGoogle Scholar
  36. 36.
    Marmarou A, Shima K. Comparative studies of edema produced by fluid percussion injury with lateral and central modes of injury in cats. Adv Neurol 52: 233–236, 1990.PubMedGoogle Scholar
  37. 37.
    Raghupathi R, McIntosh TK, Smith DH. Cellular responses to experimental brain injury. Brain Pathol 5: 437–442, 1995.PubMedGoogle Scholar
  38. 38.
    Thibault LE, Meaney DF, Anderson BJ, Marmarou A. Biomechanical aspects of a fluid percussion model of brain injury. J Neurotrauma 9: 311–322, 1992.PubMedGoogle Scholar
  39. 39.
    Vink R, Mullins PG, Temple MD, Bao W, Faden AI. Small shifts in craniotomy position in the lateral fluid percussion injury model are associated with differential lesion development. J Neurotrauma 18: 839–847, 2001.PubMedGoogle Scholar
  40. 40.
    Floyd CL, Golden KM, Black RT, Hamm RJ, Lyeth BG. Craniectomy position affects morris water maze performance and hippocampal cell loss after parasagittal fluid percussion. J Neurotrauma 19: 303–316, 2002.PubMedGoogle Scholar
  41. 41.
    Thompson HJ, Lifshitz J, Marklund N, Grady MS, Graham DI, Hovda DA, et al. Lateral fluid percussion brain injury: a 15-year review and evaluation. J Neurotrauma 22: 42–75, 2005.PubMedGoogle Scholar
  42. 42.
    Iwamoto Y, Yamaki T, Murakami N, Umeda M, Tanaka C, Higuchi T, et al. Investigation of morphological change of lateral and midline fluid percussion injury in rats, using magnetic resonance imaging. Neurosurgery 40: 163–167, 1997.PubMedGoogle Scholar
  43. 43.
    Dixon CE, Lyeth BG, Povlishock JT, Findling RL, Hamm RJ, Marmarou A, et al. A fluid percussion model of experimental brain injury in the rat. J Neurosurg 67: 110–119, 1987.PubMedGoogle Scholar
  44. 44.
    Atkinson JL, Anderson RE, Murray MJ. The early critical phase of severe head injury: importance of apnea and dysfunctional respiration. J Trauma 45: 941–945, 1998.PubMedGoogle Scholar
  45. 45.
    Qian L, Ohno K, Maehara T, Tominaga B, Hirakawa K, Kuroiwa T, et al. Changes in 1CBF, morphology and related parameters by fluid percussion injury. Acta Neurochir (Wien) 138: 90–98, 1996.Google Scholar
  46. 46.
    Muir JK, Boerschel M, Ellis EF. Continuous monitoring of post-traumatic cerebral blood flow using laser-Doppler flowmetry. J Neurotrauma 9: 355–362, 1992.PubMedGoogle Scholar
  47. 47.
    Tanno H, Nockels RP, Pitts LH, Noble LJ. Breakdown of the blood-brain barrier after fluid percussion brain injury in the rat. Part 2: effect of hypoxia on permeability to plasma proteins. J Neurotrauma 9: 335–347, 1992.PubMedGoogle Scholar
  48. 48.
    Povlishock JT, Kontos HA. Continuing axonal and vascular change following experimental brain trauma. Cent Nerv Syst Trauma 2: 285–298, 1985.PubMedGoogle Scholar
  49. 49.
    Dietrich WD, Alonso O, Halley M. Early microvascular and neuronal consequences of traumatic brain injury: a light and electron microscopic study in rats. J Neurotrauma 11: 289–301, 1994.PubMedGoogle Scholar
  50. 50.
    Pettus EH, Povlishock JT. Characterization of a distinct set of intra-axonal ultrastructural changes associated with traumatically induced alteration in axolemmal permeability. Brain Res 722: 1–11, 1996.PubMedGoogle Scholar
  51. 51.
    Wang YJ, Shimura T, Kobayashi S, Teramoto A, Nakazawa S. A lateral fluid percussion model for the experimental severe brain injury and a morphological study in the rats. Nippon Ika Daigaku Zasshi 64: 172–175, 1997.PubMedGoogle Scholar
  52. 52.
    Graham DI, Raghupathi R, Saatman KE, Meaney D, McIntosh TK. Tissue tears in the white matter after lateral fluid percussion brain injury in the rat: relevance to human brain injury. Acta Neuropathol (Berl) 99: 117–124, 2000.Google Scholar
  53. 53.
    Yakovlev AG, Knoblach SM, Fan L, Fox GB, Goodnight R, Faden AI. Activation of CPP32-like caspases contributes to neuronal apoptosis and neurological dysfunction after traumatic brain injury. J Neurosci 17: 7415–7424, 1997.PubMedGoogle Scholar
  54. 54.
    Kita T, Tanaka T, Tanaka N, Kinoshita Y. The role of tumor necrosis factor-α in diffuse axonal injury following fluid-percussive brain injury in rats. Int J Legal Med 113: 221–228, 2000.PubMedGoogle Scholar
  55. 55.
    Okiyama K, Smith DH, Thomas MJ, McIntosh TK. Evaluation of a novel calcium channel blocker, (S)-emopamil, on regional cerebral edema and neurobehavioral function after experimental brain injury. J Neurosurg 77: 607–615, 1992.PubMedGoogle Scholar
  56. 56.
    Osteen CL, Moore AH, Prins ML, Hovda DA. Age-dependency of 45calcium accumulation following lateral fluid percussion: acute and delayed patterns. J Neurotrauma 18: 141–162, 2001.PubMedGoogle Scholar
  57. 57.
    McIntosh TK, Soares H, Thomas M, Cloherty K. Development of regional cerebral oedema after lateral fluid-percussion brain injury in the rat. Acta Neurochir Suppl (Wien) 51: 263–264, 1990.Google Scholar
  58. 58.
    Soares HD, Thomas M, Cloherty K, McIntosh TK. Development of prolonged focal cerebral edema and regional cation changes following experimental brain injury in the rat. J Neurochem 58: 1845–1852, 1992.PubMedGoogle Scholar
  59. 59.
    Sun FY, Faden AI. Neuroprotective effects of 619C89, a use-dependent sodium channel blocker, in rat traumatic brain injury. Brain Res 673: 133–140, 1995.PubMedGoogle Scholar
  60. 60.
    Katayama Y, Becker DP, Tamura T, Hovda DA. Massive increases in extracellular potassium and the indiscriminate release of glutamate following concussive brain injury. J Neurosurg 73: 889–900, 1990.PubMedGoogle Scholar
  61. 61.
    D’Ambrosio R, Maris DO, Grady MS, Winn HR, Janigro D. Impaired K(+) homeostasis and altered electrophysiological properties of post-traumatic hippocampal glia. J Neurosci 19: 8152–8162, 1999.PubMedGoogle Scholar
  62. 62.
    McIntosh TK, Faden AI, Bendall MR, Vink R. Traumatic brain injury in the rat: alterations in brain lactate and pH as characterized by 1H and 31P nuclear magnetic resonance. J Neurochem 49: 1530–1540, 1987.PubMedGoogle Scholar
  63. 63.
    Vink R, McIntosh TK, Demediuk P, Weiner MW, Faden AI. Decline in intracellular free Mg2+ is associated with irreversible tissue injury after brain trauma. J Biol Chem 263: 757–761, 1988.PubMedGoogle Scholar
  64. 64.
    McIntosh TK, Faden AI, Yamakami I, Vink R. Magnesium deficiency exacerbates and pretreatment improves outcome following traumatic brain injury in rats: 31P magnetic resonance spectroscopy and behavioral studies. J Neurotrauma 5: 17–31, 1988.PubMedGoogle Scholar
  65. 65.
    Saija A, Robinson SE, Lyeth BG, Dixon CE, Yamamoto T, Clifton GL, et al. The effects of scopolamine and traumatic brain injury on central cholinergic neurons. J Neurotrauma 5: 161–170, 1988.PubMedGoogle Scholar
  66. 66.
    Vink R, Golding EM, Headrick JP. Bioenergetic analysis of oxidative metabolism following traumatic brain injury in rats. J Neurotrauma 11: 265–274, 1994.PubMedGoogle Scholar
  67. 67.
    Baker AJ, Phan N, Moulton RJ, Fehlings MG, Yucel Y, Zhao M, et al. Attenuation of the electrophysiological function of the corpus callosum after fluid percussion injury in the rat. J Neurotrauma 19: 587–599, 2002.PubMedGoogle Scholar
  68. 68.
    Hayes RL, Katayama Y, Young HF, Dunbar JG. Coma associated with flaccidity produced by fluid-percussion concussion in the cat. I: Is it due to depression of activity within the brainstem reticular formation? Brain Inj 2: 31–49, 1988.PubMedGoogle Scholar
  69. 69.
    Hamm RJ, Pike BR, O’Dell DM, Lyeth BG, Jenkins LW. The rotarod test: an evaluation of its effectiveness in assessing motor deficits following traumatic brain injury. J Neurotrauma 11: 187–196, 1994.PubMedGoogle Scholar
  70. 70.
    Smith DH, Okiyama K, Thomas MJ, Claussen B, McIntosh TK. Evaluation of memory dysfunction following experimental brain injury using the Morris water maze. J Neurotrauma 8: 259–269, 1991.PubMedGoogle Scholar
  71. 71.
    Hamm RJ, Lyeth BG, Jenkins LW, O’Dell DM, Pike BR. Selective cognitive impairment following traumatic brain injury in rats. Behav Brain Res 59: 169–173, 1993.PubMedGoogle Scholar
  72. 72.
    Hogg S, Moser PC, Sanger DJ. Mild traumatic lesion of the right parietal cortex of the rat: selective behavioural deficits in the absence of neurological impairment. Behav Brain Res 93: 143–155, 1998.PubMedGoogle Scholar
  73. 73.
    Lighthall JW. Controlled cortical impact: a new experimental brain injury model. J Neurotrauma 5: 1–15, 1988.PubMedGoogle Scholar
  74. 74.
    Dixon CE, Clifton GL, Lighthall JW, Yaghmai AA, Hayes RL. A controlled cortical impact model of traumatic brain injury in the rat. J Neurosci Methods 39: 253–262, 1991.PubMedGoogle Scholar
  75. 75.
    Goodman JC, Cherian L, Bryan RM Jr, Robertson CS. Lateral cortical impact injury in rats: pathologic effects of varying cortical compression and impact velocity. J Neurotrauma 11: 587–597, 1994.PubMedGoogle Scholar
  76. 76.
    Smith DH, Soares HD, Pierce JS, Perlman KG, Saatman KE, Meaney DF, et al. A model of parasagittal controlled cortical impact in the mouse: cognitive and histopathologic effects. J Neurotrauma 12: 169–178, 1995.PubMedGoogle Scholar
  77. 77.
    Cherian L, Robertson CS, Contant CF Jr, Bryan RM Jr. Lateral cortical impact injury in rats: cerebrovascular effects of varying depth of cortical deformation and impact velocity. J Neurotrauma 11: 573–585, 1994.PubMedGoogle Scholar
  78. 78.
    Lighthall JW, Goshgarian HG, Pinderski CR. Characterization of axonal injury produced by controlled cortical impact. J Neurotrauma 7: 65–76, 1990.PubMedGoogle Scholar
  79. 79.
    Palmer AM, Marion DW, Botscheller ML, Swedlow PE, Styren SD, DeKosky ST. Traumatic brain injury-induced excitotoxicity assessed in a controlled cortical impact model. J Neurochem 61: 2015–2024, 1993.PubMedGoogle Scholar
  80. 80.
    Fox GB, Fan L, Levasseur RA, Faden AI. Sustained sensory/ motor and cognitive deficits with neuronal apoptosis following controlled cortical impact brain injury in the mouse. J Neurotrauma 15: 599–614, 1998.PubMedGoogle Scholar
  81. 81.
    Scheff SW, Baldwin SA, Brown RW, Kraemer PJ. Morris water maze deficits in rats following traumatic brain injury: lateral controlled cortical impact. J Neurotrauma 14: 615–627, 1997.PubMedGoogle Scholar
  82. 82.
    Meaney DF, Ross DT, Winkelstein BA, Brasko J, Goldstein D, Bilston LB, et al. Modification of the cortical impact model to produce axonal injury in the rat cerebral cortex. J Neurotrauma 11: 599–612, 1994.PubMedGoogle Scholar
  83. 83.
    Matthews MA, Carey ME, Soblosky JS, Davidson JF, Tabor SL. Focal brain injury and its effects on cerebral mantle, neurons, and fiber tracks. Brain Res 794: 1–18, 1998.PubMedGoogle Scholar
  84. 84.
    Newcomb JK, Zhao X, Pike BR, Hayes RL. Temporal profile of apoptotic-like changes in neurons and astrocytes following controlled cortical impact injury in the rat. Exp Neurol 158: 76–88, 1999.PubMedGoogle Scholar
  85. 85.
    Dunn-Meynell AA, Levin BE. Histological markers of neuronal, axonal and astrocytic changes after lateral rigid impact traumatic brain injury. Brain Res 761: 25–41, 1997.PubMedGoogle Scholar
  86. 86.
    Baskaya MK, Rao AM, Dogan A, Donaldson D, Dempsey RJ. The biphasic opening of the blood-brain barrier in the cortex and hippocampus after traumatic brain injury in rats. Neurosci Lett 226: 33–36, 1997.PubMedGoogle Scholar
  87. 87.
    Bryan RM Jr, Cherian L, Robertson C. Regional cerebral blood flow after controlled cortical impact injury in rats. Anesth Analg 80: 687–695, 1995.PubMedGoogle Scholar
  88. 88.
    Prasad MR, Ramaiah C, McIntosh TK, Dempsey RJ, Hipkens S, Yurek D. Regional levels of lactate and norepinephrine after experimental brain injury. J Neurochem 63: 1086–1094, 1994.PubMedGoogle Scholar
  89. 89.
    Colicos MA, Dash PK. Apoptotic morphology of dentate gyrus granule cells following experimental cortical impact injury in rats: possible role in spatial memory deficits. Brain Res 739: 120–131, 1996.PubMedGoogle Scholar
  90. 90.
    Smith DH, Nakamura M, McIntosh TK, Wang J, Rodriguez A, Chen XH, et al. Brain trauma induces massive hippocampal neuron death linked to a surge in β-amyloid levels in mice overex-pressing mutant amyloid precursor protein. Am J Pathol 153: 1005–1010, 1998.PubMedGoogle Scholar
  91. 91.
    Kaya SS, Mahmood A, Li Y, Yavuz E, Goksel M, Chopp M. Apoptosis and expression of p53 response proteins and cyclin D1 after cortical impact in rat brain. Brain Res 818: 23–33, 1999.PubMedGoogle Scholar
  92. 92.
    Beer R, Franz G, Schopf M, Reindl M, Zeiger B, Schmutzhard E, et al. Expression of Fas and Fas ligand after experimental traumatic brain injury in the rat. J Cereb Blood Flow Metab 20: 669–677, 2000.PubMedGoogle Scholar
  93. 93.
    Matzilevich DA, Rall JM, Moore AN, Grill RJ, Dash PK. High-density microarray analysis of hippocampal gene expression following experimental brain injury. J Neurosci Res 67: 646–663, 2002.PubMedGoogle Scholar
  94. 94.
    Long Y, Zou L, Liu H, Lu H, Yuan X, Robertson CS, et al. Altered expression of randomly selected genes in mouse hippocampus after traumatic brain injury. J Neurosci Res 71: 710–720, 2003.Google Scholar
  95. 95.
    Kawamata T, Katayama Y, Maeda T, Mori T, Aoyama N, Kikuchi T, et al. Antioxidant, OPC-14117, attenuates edema formation and behavioral deficits following cortical contusion in rats. Acta Neurochir Suppl (Wien) 70: 191–193, 1997.Google Scholar
  96. 96.
    Verweij BH, Muizelaar JP, Vinas FC, Peterson PL, Xiong Y, Lee CP. Mitochondrial dysfunction after experimental and human brain injury and its possible reversal with a selective N-type calcium channel antagonist (SNX-111). Neurol Res 19: 334–339, 1997.PubMedGoogle Scholar
  97. 97.
    Faden AI, Fox GB, Fan L, Araldi GL, Qiao L, Wang S, et al. Novel TRH analog improves motor and cognitive recovery after traumatic brain injury in rodents. Am J Physiol (Lond) 277: R1196-R1204, 1999.Google Scholar
  98. 98.
    Kroppenstedt SN, Stroop R, Kern M, Thomale UW, Schneider GH, Unterberg AW. Lubeluzole following traumatic brain injury in the rat. J Neurotrauma 16: 629–637, 1999.PubMedGoogle Scholar
  99. 99.
    Dempsey RJ, Baskaya MK, Dogan A. Attenuation of brain edema, blood-brain barrier breakdown, and injury volume by ifenprodil, a polyamine-site N-methyl-D-aspartate receptor antagonist, after experimental traumatic brain injury in rats. Neurosurgery 47: 399–404, 2000.PubMedGoogle Scholar
  100. 100.
    Sullivan PG, Thompson M, Scheff SW. Continuous infusion of cyclosporin A postinjury significantly ameliorates cortical damage following traumatic brain injury. Exp Neurol 161: 631–637, 2000.PubMedGoogle Scholar
  101. 101.
    Di X, Zhang T, Mullins P, Faden AI. Novel, potent, and selective group II mGluR agonist LY379268 ameliorates cognitive and motor deficits induced by control cortical impact injury in mouse. J Neurotrauma 17: 960, 2000.Google Scholar
  102. 102.
    Faden AI, Fox GB, Di X, Knoblach SM, Cemak I, Mullins P, et al. Neuroprotective and nootropic actions of a novel cyclized dipeptide after controlled cortical impact injury in mice. J Cereb Blood Flow Metab 23: 355–363, 2003.PubMedGoogle Scholar
  103. 103.
    Shreiber DI, Bain AC, Ross DT, Smith DH, Gennarelli TA, McIntosh TK, et al. Experimental investigation of cerebral contusion: histopathological and immunohistochemical evaluation of dynamic cortical deformation. J Neuropathol Exp Neurol 58: 153–164, 1999.PubMedGoogle Scholar
  104. 104.
    Shreiber DI, Smith DH, Meaney DF. Immediate in vivo response of the cortex and the blood-brain barrier following dynamic cortical deformation in the rat. Neurosci Lett 259: 5–8, 1999.PubMedGoogle Scholar
  105. 105.
    Fitch MT, Doller C, Combs CK, Landreth GE, Silver J. Cellular and molecular mechanisms of glial scarring and progressive cavitation: in vivo and in vitro analysis of inflammation-induced secondary injury after CNS trauma. J Neurosci 19: 8182–8198, 1999.PubMedGoogle Scholar
  106. 106.
    Mathew P, Bullock R, Graham DI, Maxwell WL, Teasdale GM, McCulloch J. A new experimental model of contusion in the rat. Histopathological analysis and temporal patterns of cerebral blood flow disturbances. J Neurosurg 85: 860–870, 1996.PubMedGoogle Scholar
  107. 107.
    Sun D, Tani M, Newman TA, Krivacic K, Phillips M, Chemosky A, et al. Role of chemokines, neuronal projections, and the blood-brain barrier in the enhancement of cerebral EAE following focal brain damage. J Neuropathol Exp Neurol 59: 1031–1043, 2000.PubMedGoogle Scholar
  108. 108.
    Ghirnikar RS, Lee YL, He TR, Eng LF. Chemokine expression in rat stab wound brain injury. J Neurosci Res 46: 727–733, 1996.PubMedGoogle Scholar
  109. 109.
    Burger R, Bendszus M, Vince GH, Roosen K, Marmarou A. A new reproducible model of an epidural mass lesion in rodents. Part I: characterization by neurophysiological monitoring, magnetic resonance imaging, and histopathological analysis. J Neurosurg 97: 1410–1418, 2002.PubMedGoogle Scholar
  110. 110.
    Allen IV, Scott R, Tanner JA. Experimental high-velocity missile head injury. Injury 14: 183–193, 1982.PubMedGoogle Scholar
  111. 111.
    Carey ME, Sarna GS, Farrell JB. Brain edema following an experimental missile wound to the brain. J Neurotrauma 7: 13–20, 1990.PubMedGoogle Scholar
  112. 112.
    Finnie JW. Pathology of experimental traumatic craniocerebral missile injury. J Comp Pathol 108: 93–101, 1993.PubMedGoogle Scholar
  113. 113.
    Finnie JW. Brain damage caused by a captive bolt pistol. J Comp Pathol 109: 253–258, 1993.PubMedGoogle Scholar
  114. 114.
    Carey ME. Experimental missile wounding of the brain. Neurosurg Clin N Am 6: 629–642, 1995.PubMedGoogle Scholar
  115. 115.
    Carey ME, Sarna GS, Farrell JB. Brain edema after an experimental missile wound. Adv Neurol 52: 301–305, 1990.PubMedGoogle Scholar
  116. 116.
    Carey ME, Sama GS, Farrell JB, Happel LT. Experimental missile wound to the brain. J Neurosurg 71: 754–764, 1989.PubMedGoogle Scholar
  117. 117.
    Beckman DL, Bean JW. Pulmonary pressure-volume changes attending head injury. J Appl Physiol 29: 631–636, 1970.PubMedGoogle Scholar
  118. 118.
    Bakay L, Lee JC, Lee GC, Peng JR. Experimental cerebral concussion. Part 1: An electron microscopic study. J Neurosurg 47: 525–531, 1977.PubMedGoogle Scholar
  119. 119.
    Nilsson B, Ponten U, Voigt G. Experimental head injury in the rat. Part 1: mechanics, pathophysiology, and morphology in an impact acceleration trauma model. J Neurosurg 47: 241–251, 1977.PubMedGoogle Scholar
  120. 120.
    Lighthall JW, Dixon CE, Anderson TE. Experimental models of brain injury. J Neurotrauma 6: 83–97, 1989.PubMedGoogle Scholar
  121. 121.
    Tomheim PA, McLaurin RL. Acute changes in regional brain water content following experimental closed head injury. J Neurosurg 55: 407–413, 1981.Google Scholar
  122. 122.
    Tomheim PA, McDermott F, Shiguma M. Effect of experimental blunt head injury on acute regional cerebral blood flow and edema. Adv Neurol 52: 377–384, 1990.Google Scholar
  123. 123.
    Tomheim PA, Liwnicz BH, Hirsch CS, Brown DL, McLaurin RL. Acute responses to blunt head trauma. Experimental model and gross pathology. J Neurosurg 59: 431–438, 1983.Google Scholar
  124. 124.
    Wagner KR, Tomheim PA, Eichhold MK. Acute changes in regional cerebral metabolite values following experimental blunt head trauma. J Neurosurg 63: 88–96, 1985.PubMedGoogle Scholar
  125. 125.
    Goldman H, Hodgson V, Morehead M, Hazlett J, Murphy S. Cerebrovascular changes in a rat model of moderate closed-head injury. J Neurotrauma 8: 129–144, 1991.PubMedGoogle Scholar
  126. 126.
    Morehead M, Bartus RT, Dean RL, Miotke JA, Murphy S, Sall J, et al. Histopathologic consequences of moderate concussion in an animal model: correlations with duration of unconsciousness. J Neurotrauma 11: 657–667, 1994.PubMedGoogle Scholar
  127. 127.
    Gurdjian ES, Lissner HR, Webster JE, Latimer FR, Haddad BF. Studies on experimental concussion. Neurology 4: 674–681, 1954.PubMedGoogle Scholar
  128. 128.
    Ommaya AK, Grubb RL Jr, Naumann RA. Coup and contre-coup injury: observations on the mechanics of visible brain injuries in the rhesus monkey. J Neurosurg 35: 503–516, 1971.PubMedGoogle Scholar
  129. 129.
    Lewis SB, Finnie JW, Blumbergs PC, Scott G, Manavis J, Brown C, et al. A head impact model of early axonal injury in the sheep. J Neurotrauma 13: 505–514, 1996.PubMedGoogle Scholar
  130. 130.
    Van Den Heuvel C, Lewis S, Wong M, Manavis J, Finnie J, Blumbergs P, et al. Diffuse neuronal perikaryon amyloid precursor protein immunoreactivity in a focal head impact model. Acta Neurochir Suppl 71: 209–211, 1998.Google Scholar
  131. 131.
    Gosch HH, Gooding E, Schneider RC. The lexan calvarium for the study of cerebral responses to acute trauma. J Trauma 10: 370–376, 1970.PubMedGoogle Scholar
  132. 132.
    Marmarou A, Foda MA, van den Brink W, Campbell J, Kita H, Demetriadou K. A new model of diffuse brain injury in rats. Part I: Pathophysiology and biomechanics. J Neurosurg 80: 291–300, 1994.PubMedGoogle Scholar
  133. 133.
    Foda MA, Marmarou A. A new model of diffuse brain injury in rats. Part II: Morphological characterization. J Neurosurg 80: 301–313, 1994.PubMedGoogle Scholar
  134. 134.
    Piper IR, Thomson D, Miller JD. Monitoring weight drop velocity and foam stiffness as an aid to quality control of a rodent model of impact acceleration neurotrauma. J Neurosci Methods 69: 171–174, 1996.PubMedGoogle Scholar
  135. 135.
    De Mulder G, Van Rossem K, Van Reempts J, Borgers M, Verlooy J. Validation of a closed head injury model for use in long-term studies. Acta Neurochir Suppl 76: 409–413, 2000.PubMedGoogle Scholar
  136. 136.
    Folkerts MM, Berman RF, Muizelaar JP, Rafols JA. Disruption of MAP-2 immunostaining in rat hippocampus after traumatic brain injury. J Neurotrauma 15: 349–363, 1998.PubMedGoogle Scholar
  137. 137.
    Kallakuri S, Cavanaugh JM, Ozaktay AC, Takebayashi T. The effect of varying impact energy on diffuse axonal injury in the rat brain: a preliminary study. Exp Brain Res 148: 419–424, 2003.PubMedGoogle Scholar
  138. 138.
    Povlishock JT, Marmarou A, McIntosh T, Trojanowski JQ, Moroi J. Impact acceleration injury in the rat: evidence for focal axolemmal change and related neurofilament sidearm alteration. J Neuropathol Exp Neurol 56: 347–359, 1997.PubMedGoogle Scholar
  139. 139.
    Engelborghs K, Verlooy J, Van Deuren B, Van Reempts J, Borgers M. Intracranial pressure in a modified experimental model of closed head injury. Acta Neurochir Suppl (Wien) 70: 123–125, 1997.Google Scholar
  140. 140.
    Prat R, Markiv V, Dujovny M, Misra M. Failure of cerebral autoregulation in an experimental diffuse brain injury model. Acta Neurochir Suppl (Wien) 71: 123–126, 1998.Google Scholar
  141. 141.
    Barzo P, Marmarou A, Fatouros P, Hayasaki K, Corwin F. Biphasic pathophysiological response of vasogenic and cellular edema in traumatic brain swelling. Acta Neurochir Suppl (Wien) 70: 119–122, 1997.Google Scholar
  142. 142.
    Heath DL, Vink R. Impact acceleration-induced severe diffuse axonal injury in rats: characterization of phosphate metabolism and neurologic outcome. J Neurotrauma 12: 1027–1034, 1995.PubMedGoogle Scholar
  143. 143.
    Schmidt RH, Scholten KJ, Maughan PH. Cognitive impairment and synaptosomal choline uptake in rats following impact acceleration injury. J Neurotrauma 17: 1129–1139, 2000.PubMedGoogle Scholar
  144. 144.
    Vink R, O’Connor CA, Nimmo AJ, Heath DL. Magnesium attenuates persistent functional deficits following diffuse traumatic brain injury in rats. Neurosci Lett 336: 41–44, 2003.PubMedGoogle Scholar
  145. 145.
    Vagnozzi R, Marmarou A, Tavazzi B, Signoretti S, Di Pierro D, del Bolgia F, et al. Changes of cerebral energy metabolism and lipid peroxidation in rats leading to mitochondrial dysfunction after diffuse brain injury. J Neurotrauma 16: 903–913, 1999.PubMedGoogle Scholar
  146. 146.
    Signoretti S, Marmarou A, Tavazzi B, Lazzarino G, Beaumont A, Vagnozzi R. N-acetylaspartate reduction as a measure of injury severity and mitochondrial dysfunction following diffuse traumatic brain injury. J Neurotrauma 18: 977–991, 2001.PubMedGoogle Scholar
  147. 147.
    Cemak I, O’Connor C, Vink R. Activation of cyclo-oxygenase-2 contributes to motor and cognitive dysfunction following diffuse traumatic brain injury in rats. Clin Exp Pharmacol Physiol 28: 922–925, 2001.Google Scholar
  148. 148.
    Rhodes JK, Andrews PJ, Holmes MC, Seckl JR. Expression of interleukin-6 messenger RNA in a rat model of diffuse axonal injury. Neurosci Lett 335: 1–4, 2002.PubMedGoogle Scholar
  149. 149.
    Cemak I, O’Connor C, Vink R. Inhibition of cyclooxygenase 2 by nimesulide improves cognitive outcome more than motor outcome following diffuse traumatic brain injury in rats. Exp Brain Res 147: 193–199, 2002.Google Scholar
  150. 150.
    Buki A, Okonkwo DO, Wang KK, Povlishock JT. Cytochrome c release and caspase activation in traumatic axonal injury. J Neurosci 20: 2825–2834, 2000.PubMedGoogle Scholar
  151. 151.
    Cemak I, Chapman SM, Hamlin GP, Vink R. Temporal characterisation of pro- and anti-apoptotic mechanisms following diffuse traumatic brain injury in rats. J Clin Neurosci 9: 565–572, 2002.Google Scholar
  152. 152.
    Cemak I, Vink R, Zapple DN, Cruz MI, Ahmed F, Chang T, et al. The pathobiology of moderate diffuse traumatic brain injury as identified using a new experimental model of injury in rats. Neurobiol Dis 17: 29–43, 2004.Google Scholar
  153. 153.
    Holboum AH. Mechanics of head injuries. Lancet 2: 438–441, 1943.Google Scholar
  154. 154.
    Meythaler JM, Peduzzi JD, Eleftheriou E, Novack TA. Current concepts: diffuse axonal injury-associated traumatic brain injury. Arch Phys Med Rehabil 82: 1461–1471, 2001.PubMedGoogle Scholar
  155. 155.
    Margulies SS, Thibault LE. An analytical model of traumatic diffuse brain injury. J Biomech Eng 111: 241–249, 1989.PubMedGoogle Scholar
  156. 156.
    Meaney DF, Margulies SS, Smith DH. Diffuse axonal injury. J Neurosurg 95: 1108–1110, 2001.PubMedGoogle Scholar
  157. 157.
    Gennarelli TA, Actams JH, Graham DI. Acceleration induced head injury in the monkey. I. The model, its mechanical and physiological correlates. Acta Neuropathol Suppl (Berl) 7: 23–25, 1981.Google Scholar
  158. 158.
    Gennarelli TA. Head injury in man and experimental animals: clinical aspects. Acta Neurochir Suppl (Wien) 32: 1–13, 1983.Google Scholar
  159. 159.
    Ross DT, Meaney DF, Sabol MK, Smith DH, Gennarelli TA. Distribution of forebrain diffuse axonal injury following inertial closed head injury in miniature swine. Exp Neurol 126: 291–299, 1994.PubMedGoogle Scholar
  160. 160.
    Smith DH, Chen XH, Xu BN, McIntosh TK, Gennarelli TA, Meaney DF. Characterization of diffuse axonal pathology and selective hippocampal damage following inertial brain trauma in the pig. J Neuropathol Exp Neurol 56: 822–834, 1997.PubMedGoogle Scholar
  161. 161.
    Gutierrez E, Huang Y, Haglid K, Bao F, Hansson HA, Hamberger A, et al. A new model for diffuse brain injury by rotational acceleration: I model, gross appearance, and astrocytosis. J Neurotrauma 18: 247–257, 2001.PubMedGoogle Scholar
  162. 162.
    Xiao-Sheng H, Sheng-Yu Y, Xiang Z, Zhou F, Jian-ning Z. Diffuse axonal injury due to lateral head rotation in a rat model. J Neurosurg 93: 626–633, 2000.PubMedGoogle Scholar
  163. 163.
    Gennarelli TA, Thibault LE, Actams JH, Graham DI, Thompson CJ, Marcincin RP. Diffuse axonal injury and traumatic coma in the primate. Ann Neurol 12: 564–574, 1982.PubMedGoogle Scholar
  164. 164.
    Meaney DF, Smith DH, Shreiber DI, Bain AC, Miller RT, Ross DT, et al. Biomechanical analysis of experimental diffuse axonal injury. J Neurotrauma 12: 689–694, 1995.PubMedGoogle Scholar
  165. 165.
    Cecil KM, Lenkinski RE, Meaney DF, McIntosh TK, Smith DH. High-field proton magnetic resonance spectroscopy of a swine model for axonal injury. J Neurochem 70: 2038–2044, 1998.PubMedGoogle Scholar
  166. 166.
    Gentleman SM, Nash MJ, Sweeting CJ, Graham DI, Roberts GW. β-Amyloid precursor protein (βAPP) as a marker for axonal injury after head injury. Neurosci Lett 160: 139–144, 1993.PubMedGoogle Scholar
  167. 167.
    Sherriff FE, Bridges LR, Sivaloganathan S. Early detection of axonal injury after human head trauma using immunocytochemistry for β-amyloid precursor protein. Acta Neuropathol (Berl) 87: 55–62, 1994.Google Scholar
  168. 168.
    Smith D, Chen X, Nonaka M, Trojanowski J, Lee V, Saatman K, et al. Accumulation of amyloid β and τ and the formation of neurofilament inclusions following diffuse brain injury in the pig. J Neuropathol Exp Neurol 58: 982–992, 1999.PubMedGoogle Scholar
  169. 169.
    Smith DH, Nonaka M, Miller R, Leoni M, Chen XH, Alsop D, et al. Immediate coma following inertial brain injury dependent on axonal damage in the brainstem. J Neurosurg 93: 315–322, 2000.PubMedGoogle Scholar
  170. 170.
    Smith DH, Cecil KM, Meaney DF, Chen XH, McIntosh TK, Gennarelli TA, et al. Magnetic resonance spectroscopy of diffuse brain trauma in the pig. J Neurotrauma 15: 665–674, 1998.PubMedGoogle Scholar
  171. 171.
    Clemedson CJ. Blast injury. Physiol Rev 36: 336–354, 1956.PubMedGoogle Scholar
  172. 172.
    Cemak I, Savic J, Malicevic Z, Zunic G, Radosevic P, Ivanovic I, et al. Involvement of the central nervous system in the general response to pulmonary blast injury. J Trauma 40: S100-S104, 1996.Google Scholar
  173. 173.
    Cemak I, Wang Z, Jiang J, Bian X, Savic J. Ultrastructural and functional characteristics of blast injury-induced neurotrauma. J Trauma 50: 695–706, 2001.Google Scholar
  174. 174.
    Saljo A, Bao F, Haglid KG, Hansson HA. Blast exposure causes redistribution of phosphorylated neurofilament subunits in neurons of the adult rat brain. J Neurotrauma 17: 719–726, 2000.PubMedGoogle Scholar
  175. 175.
    Cemak I, Wang Z, Jiang J, Bian X, Savic J. Cognitive deficits following blast injury-induced neurotrauma: possible involvement of nitric oxide. Brain Inj 15: 593–612, 2001.Google Scholar
  176. 176.
    Cemak I, Savic J, Ignjatovic D, Jevtic M. Blast injury from explosive munitions. J Trauma 47: 96–103; discussion 103–104, 1999.Google Scholar
  177. 177.
    Cemak I, Savic VJ, Kotur J, Prokic V, Veljovic M, Grbovic D. Characterization of plasma magnesium concentration and oxidative stress following graded traumatic brain injury in humans. J Neurotrauma 17: 53–68, 2000.Google Scholar
  178. 178.
    Ishige N, Pitts LH, Berry I, Carlson SG, Nishimura MC, Moseley ME, et al. The effect of hypoxia on traumatic head injury in rats: alterations in neurologic function, brain edema, and cerebral blood flow. J Cereb Blood Flow Metab 7: 759–767, 1987.PubMedGoogle Scholar
  179. 179.
    Ishige N, Pitts LH, Berry I, Nishimura MC, James TL. The effects of hypovolemic hypotension on high-energy phosphate metabolism of traumatized brain in rats. J Neurosurg 68: 129–136, 1988.PubMedGoogle Scholar
  180. 180.
    Chen M, Clark RS, Kochanek PM, Chen J, Schiding JK, Stetler RA, et al. 72-kDa heat shock protein and mRNA expression after controlled cortical impact injury with hypoxemia in rats. J Neurotrauma 15: 171–181, 1998.PubMedGoogle Scholar
  181. 181.
    Graham DI, Ford I, Actams JH, Doyle D, Teasdale GM, Lawrence AE, et al. Ischaemic brain damage is still common in fatal non-missile head injury. J Neurol Neurosurg Psychiatry 52: 346–350, 1982.Google Scholar
  182. 182.
    Chesnut RM. Secondary brain insults after head injury: clinical perspectives. New Horiz 3: 366–375, 1995.PubMedGoogle Scholar
  183. 183.
    Manley G, Knudson MM, Morabito D, Damron S, Erickson V, Pitts L. Hypotension, hypoxia, and head injury: frequency, duration, and consequences. Arch Surg 136: 1118–1123, 2001.PubMedGoogle Scholar
  184. 184.
    Bramlett HM, Green EJ, Dietrich WD. Exacerbation of cortical and hippocampal CA1 damage due to posttraumatic hypoxia following moderate fluid-percussion brain injury in rats. J Neurosurg 91: 653–659, 1999.PubMedGoogle Scholar
  185. 185.
    Beaumont A, Marmarou A, Fatouros P, Corwin F. Secondary insults worsen blood brain barrier dysfunction assessed by MRI in cerebral contusion. Acta Neurochir Suppl 81: 217–219, 2002.PubMedGoogle Scholar
  186. 186.
    Ditelberg JS, Sheldon RA, Epstein CJ, Ferriero DM. Brain injury after perinatal hypoxia-ischemia is exacerbated in copper/zinc Superoxide dismutase transgenic mice. Pediatr Res 39: 204–208, 1996.PubMedGoogle Scholar
  187. 187.
    Kimelberg HK, Cragoe EJ Jr, Nelson LR, Popp AJ, Szarowski D, Rose JW, et al. Improved recovery from a traumatic-hypoxic brain injury in cats by intracisternal injection of an anion transport inhibitor. Cent Nerv Syst Trauma 4: 3–14, 1987.PubMedGoogle Scholar
  188. 188.
    Zink BJ, Stern SA, Wang X, Chudnofsky CC. Effects of ethanol in an experimental model of combined traumatic brain injury and hemorrhagic shock. Acad Emerg Med 5: 9–17, 1998.PubMedGoogle Scholar
  189. 189.
    Stem SA, Zink BJ, Mertz M, Wang X, Dronen SC. Effect of initially limited resuscitation in a combined model of fluid-percussion brain injury and severe uncontrolled hemorrhagic shock. J Neurosurg 93: 305–314, 2000.Google Scholar
  190. 190.
    Bramlett HM, Dietrich WD, Green EJ. Secondary hypoxia following moderate fluid percussion brain injury in rats exacerbates sensorimotor and cognitive deficits. J Neurotrauma 16: 1035–1047, 1999.PubMedGoogle Scholar
  191. 191.
    Matsushita Y, Shima K, Nawashiro H, Wada K. Real-time monitoring of glutamate following fluid percussion brain injury with hypoxia in the rat. J Neurotrauma 17: 143–153, 2000.PubMedGoogle Scholar
  192. 192.
    Clark RS, Kochanek PM, Dixon CE, Chen M, Marion DW, Heineman S, et al. Early neuropathologic effects of mild or moderate hypoxemia after controlled cortical impact injury in rats. J Neurotrauma 14: 179–189, 1997.PubMedGoogle Scholar
  193. 193.
    Cai Z, Schools GP, Kimelberg HK. Metabotropic glutamate receptors in acutely isolated hippocampal astrocytes: developmental changes of mGluR5 mRNA and functional expression. Glia 29: 70–80, 2000.PubMedGoogle Scholar
  194. 194.
    Nawashiro H, Shima K, Chigasaki H. Selective vulnerability of hippocampal CA3 neurons to hypoxia after mild concussion in the rat. Neurol Res 17: 455–460, 1995.PubMedGoogle Scholar
  195. 195.
    Katoh H, Sima K, Nawashiro H, Wada K, Chigasaki H. The effect of MK-801 on extracellular neuroactive amino acids in hippocampus after closed head injury followed by hypoxia in rats. Brain Res 758: 153–162, 1997.PubMedGoogle Scholar
  196. 196.
    Yamamoto M, Marmarou CR, Stiefel MF, Beaumont A, Marmarou A. Neuroprotective effect of hypothermia on neuronal injury in diffuse traumatic brain injury coupled with hypoxia and hypotension. J Neurotrauma 16: 487–500, 1999.PubMedGoogle Scholar
  197. 197.
    Johansson CB, Lothian C, Molin M, Okano H, Lendahl U. Nestin enhancer requirements for expression in normal and injured adult CNS. J Neurosci Res 69: 784–794, 2002.PubMedGoogle Scholar
  198. 198.
    Yoburn BC, Lutfy K, Candido J. Species differences in μ- and δ-opioid receptors. Eur J Pharmacol 193: 105–108, 1991.PubMedGoogle Scholar
  199. 199.
    Rink A, Fung KM, Trojanowski JQ, Lee VM, Neugebauer E, McIntosh TK. Evidence of apoptotic cell death after experimental traumatic brain injury in the rat. Am J Pathol 147: 1575–1583, 1995.PubMedGoogle Scholar
  200. 200.
    Faden AI. Experimental neurobiology of central nervous system trauma. Crit Rev Neurobiol 7: 175–186, 1993.PubMedGoogle Scholar
  201. 201.
    Yakovlev AG, Faden AI. Molecular biology of CNS injury. J Neurotrauma 12: 767–777, 1995.PubMedGoogle Scholar
  202. 202.
    Faden AI. Pharmacologic treatment of acute traumatic brain injury. JAMA 276: 569–570, 1996.PubMedGoogle Scholar
  203. 203.
    McIntosh TK, Juhler M, Wieloch T. Novel pharmacologic strategies in the treatment of experimental traumatic brain injury: 1998. J Neurotrauma 15: 731–769, 1998.PubMedGoogle Scholar
  204. 204.
    Faden AI. Neuroprotection and traumatic brain injury: theoretical option or realistic proposition. Curr Opin Neurol 15: 707–712, 2002.PubMedGoogle Scholar
  205. 205.
    Vink R, Nimmo AJ. Novel therapies in development for the treatment of traumatic brain injury. Expert Opin Investig Drugs 11: 1375–1386, 2002.PubMedGoogle Scholar
  206. 206.
    Faden AI. Neuroprotection and traumatic brain injury: the search continues. Arch Neurol 58: 1553–1555, 2001.PubMedGoogle Scholar
  207. 207.
    Faden AI. Comparison of single and combination drug treatment strategies in experimental brain trauma. J Neurotrauma 10: 91–100, 1993.PubMedGoogle Scholar

Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc 2005

Authors and Affiliations

  1. 1.Department of NeuroscienceGeorgetown University Medical CenterWashington, D.C.

Personalised recommendations