Mild head injury increasing the brain's vulnerability to a second concussive impact

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  • 1 The Head Injury Center, Department of Neurosurgery, and Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine; and The Veterans Administration Medical Center, Philadelphia, Pennsylvania
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Object. Mild, traumatic repetitive head injury (RHI) leads to neurobehavioral impairment and is associated with the early onset of neurodegenerative disease. The authors developed an animal model to investigate the behavioral and pathological changes associated with RHI.

Methods. Adult male C57BL/6 mice were subjected to a single injury (43 mice), repetitive injury (two injuries 24 hours apart; 49 mice), or no impact (36 mice). Cognitive function was assessed using the Morris water maze test, and neurological motor function was evaluated using a battery of neuroscore, rotarod, and rotating pole tests. The animals were also evaluated for cardiovascular changes, blood—brain barrier (BBB) breakdown, traumatic axonal injury, and neurodegenerative and histopathological changes between 1 day and 56 days after brain trauma. No cognitive dysfunction was detected in any group. The single-impact group showed mild impairment according to the neuroscore test at only 3 days postinjury, whereas RHI caused pronounced deficits at 3 days and 7 days following the second injury. Moreover, RHI led to functional impairment during the rotarod and rotating pole tests that was not observed in any animal after a single impact. Small areas of cortical BBB breakdown and axonal injury, observed after a single brain injury, were profoundly exacerbated after RHI. Immunohistochemical staining for microtubule-associated protein—2 revealed marked regional loss of immunoreactivity only in animals subjected to RHI. No deposits of β-amyloid or tau were observed in any brain-injured animal.

Conclusions. On the basis of their results, the authors suggest that the brain has an increased vulnerability to a second traumatic insult for at least 24 hours following an initial episode of mild brain trauma.

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Contributor Notes

Address reprint requests to: Tracy K. McIntosh, M.D., Department of Neurosurgery, University of Pennsylvania School of Medicine, 105 Hayden Hall, 3320 Smith Walk, Philadelphia, Pennsylvania 19104–6316. email: mcintosh@seas.upenn.edu.
  • 1.

    Bareyre FM, , Saatman KE, & Helfaer MA, et al. : Alterations in ionized and total blood magnesium after experimental traumatic brain injury: relationship to neurobehavioral outcome and neuroprotective efficacy of magnesium chloride. J Neurochem 73:271280, 1999 Bareyre FM, Saatman KE, Helfaer MA, et al: Alterations in ionized and total blood magnesium after experimental traumatic brain injury: relationship to neurobehavioral outcome and neuroprotective efficacy of magnesium chloride. J Neurochem 73:271–280, 1999

    • Search Google Scholar
    • Export Citation
  • 2.

    Barone FC, , White RF, & Spera PA, et al. : Ischemic preconditioning and brain tolerance: temporal histological and functional outcomes, protein synthesis requirement, and interleukin-1 receptor antagonist and early gene expression. Stroke 29:19371951, 1998 Barone FC, White RF, Spera PA, et al: Ischemic preconditioning and brain tolerance: temporal histological and functional outcomes, protein synthesis requirement, and interleukin-1 receptor antagonist and early gene expression. Stroke 29:1937–1951, 1998

    • Search Google Scholar
    • Export Citation
  • 3.

    Beck WT, , Mandel HG, & Fabro S: Physiological disposition of pentobarbital in tumor-bearing mice. Cancer Res 35:13331340, 1975 Beck WT, Mandel HG, Fabro S: Physiological disposition of pentobarbital in tumor-bearing mice. Cancer Res 35:1333–1340, 1975

    • Search Google Scholar
    • Export Citation
  • 4.

    Bijur PE, , Haslum M, & Golding J: Cognitive outcomes of multiple mild head injuries in children. J Dev Behav Pediatr 17:143148, 1996 Bijur PE, Haslum M, Golding J: Cognitive outcomes of multiple mild head injuries in children. J Dev Behav Pediatr 17:143–148, 1996

    • Search Google Scholar
    • Export Citation
  • 5.

    Blasko I, , Marx F, & Steiner E, et al. : TNFα plus IFNγ induce the production of Alzheimer β-amyloid peptides and decrease the secretion of APPs. FASEB J 13:6368, 1999 Blasko I, Marx F, Steiner E, et al: TNFα plus IFNγ induce the production of Alzheimer β-amyloid peptides and decrease the secretion of APPs. FASEB J 13:63–68, 1999

    • Search Google Scholar
    • Export Citation
  • 6.

    Blumbergs PC, , Scott G, & Manavis J, et al. : Topography of axonal injury as defined by amyloid precursor protein and the sector scoring method in mild and severe closed head injury. J Neurotrauma 12:565572, 1995 Blumbergs PC, Scott G, Manavis J, et al: Topography of axonal injury as defined by amyloid precursor protein and the sector scoring method in mild and severe closed head injury. J Neurotrauma 12:565–572, 1995

    • Search Google Scholar
    • Export Citation
  • 7.

    Bohnen N, & Jolles J: Neurobehavioral aspects of postconcussive symptoms after mild head injury. J Nerv Ment Dis 180:683692, 1992 Bohnen N, Jolles J: Neurobehavioral aspects of postconcussive symptoms after mild head injury. J Nerv Ment Dis 180:683–692, 1992

    • Search Google Scholar
    • Export Citation
  • 8.

    Cantu RC: Return to play guidelines after a head injury. Clin Sports Med 17:4560, 1998 Cantu RC: Return to play guidelines after a head injury. Clin Sports Med 17:45–60, 1998

    • Search Google Scholar
    • Export Citation
  • 9.

    Cantu RC, & Voy R: Case report: second impact syndrome: a risk in any contact sport. Physician Sportsmed 23:2734, 1995 Cantu RC, Voy R: Case report: second impact syndrome: a risk in any contact sport. Physician Sportsmed 23:27–34, 1995

    • Search Google Scholar
    • Export Citation
  • 10.

    Carbonell WS, & Grady MS: Regional and temporal characterization of neuronal, glial, and axonal response after traumatic brain injury in the mouse. Acta Neuropathol 98:396406, 1999 Carbonell WS, Grady MS: Regional and temporal characterization of neuronal, glial, and axonal response after traumatic brain injury in the mouse. Acta Neuropathol 98:396–406, 1999

    • Search Google Scholar
    • Export Citation
  • 11.

    Carbonell WS, , Maris DO, & McCall T, et al. : Adaptation of the fluid percussion injury model to the mouse. J Neurotrauma 15:217229, 1998 Carbonell WS, Maris DO, McCall T, et al: Adaptation of the fluid percussion injury model to the mouse. J Neurotrauma 15:217–229, 1998

    • Search Google Scholar
    • Export Citation
  • 12.

    Chen Y, , Constantini S, & Trembovler V, et al. : An experimental model of closed head injury in mice: pathophysiology, histopathology, and cognitive deficits. J Neurotrauma 13:557568, 1996 Chen Y, Constantini S, Trembovler V, et al: An experimental model of closed head injury in mice: pathophysiology, histopathology, and cognitive deficits. J Neurotrauma 13:557–568, 1996

    • Search Google Scholar
    • Export Citation
  • 13.

    Chorley JN: Sports-related head injuries. Curr Opin Pediatr 10:350355, 1998 Chorley JN: Sports-related head injuries. Curr Opin Pediatr 10:350–355, 1998

    • Search Google Scholar
    • Export Citation
  • 14.

    Clark RS, , Kochanek PM, & Dixon CE, et al. : Early neuropathologic effects of mild or moderate hypoxemia after controlled cortical impact injury in rats. J Neurotrauma 14:179189, 1997 Clark RS, Kochanek PM, Dixon CE, et al: Early neuropathologic effects of mild or moderate hypoxemia after controlled cortical impact injury in rats. J Neurotrauma 14:179–189, 1997

    • Search Google Scholar
    • Export Citation
  • 15.

    Collins MW, , Grindel SH, & Lovell MR, et al. : Relationship between concussion and neuropsychological performance in college football players. JAMA 282:964970, 1999 Collins MW, Grindel SH, Lovell MR, et al: Relationship between concussion and neuropsychological performance in college football players. JAMA 282:964–970, 1999

    • Search Google Scholar
    • Export Citation
  • 16.

    Dixon CE, , Clifton GL, & Lighthall JW, et al. : A controlled cortical impact model of traumatic brain injury in the rat. J Neurosci Methods 39:253262, 1991 Dixon CE, Clifton GL, Lighthall JW, et al: A controlled cortical impact model of traumatic brain injury in the rat. J Neurosci Methods 39:253–262, 1991

    • Search Google Scholar
    • Export Citation
  • 17.

    Dixon CE, , Hamm RJ, & Taft WC, et al. : Increased anticholinergic sensitivity following closed skull impact and controlled cortical impact traumatic brain injury in the rat. J Neurotrauma 11:275287, 1994 Dixon CE, Hamm RJ, Taft WC, et al: Increased anticholinergic sensitivity following closed skull impact and controlled cortical impact traumatic brain injury in the rat. J Neurotrauma 11:275–287, 1994

    • Search Google Scholar
    • Export Citation
  • 18.

    Duhaime AC, , Christian CW, & Rorke LB, et al. : Nonaccidental head injury in infants—the “shaken-baby syndrome.” N Engl J Med 338:18221829, 1998 Duhaime AC, Christian CW, Rorke LB, et al: Nonaccidental head injury in infants—the “shaken-baby syndrome.” N Engl J Med 338:1822–1829, 1998

    • Search Google Scholar
    • Export Citation
  • 19.

    Fineman I, , Hovda DA, & Smith M, et al. : Concussive brain injury is associated with a prolonged accumulation of calcium: a 45Ca autoradiographic study. Brain Res 624:94102, 1993 Fineman I, Hovda DA, Smith M, et al: Concussive brain injury is associated with a prolonged accumulation of calcium: a 45Ca autoradiographic study. Brain Res 624:94–102, 1993

    • Search Google Scholar
    • Export Citation
  • 20.

    Folkerts MM, , Berman RF, & Muizelaar JP, et al. : Disruption of MAP-2 immunostaining in rat hippocampus after traumatic brain injury. J Neurotrauma 15:349363, 1998 Folkerts MM, Berman RF, Muizelaar JP, et al: Disruption of MAP-2 immunostaining in rat hippocampus after traumatic brain injury. J Neurotrauma 15:349–363, 1998

    • Search Google Scholar
    • Export Citation
  • 21.

    Fox GB, , Fan L, & Levasseur RA, et al. : Sustained sensory/motor and cognitive deficits with neuronal apoptosis following controlled cortical impact brain injury in the mouse. J Neurotrauma 15:599614, 1998 Fox GB, Fan L, Levasseur RA, et al: Sustained sensory/motor and cognitive deficits with neuronal apoptosis following controlled cortical impact brain injury in the mouse. J Neurotrauma 15:599–614, 1998

    • Search Google Scholar
    • Export Citation
  • 22.

    Fox GB, , Levasseur RA, & Faden AI: Behavioral responses of C57BL/6, FVB/N, and 129/SvEMS mouse strains to traumatic brain injury: implications for gene targeting approaches to neurotrauma. J Neurotrauma 16:377389, 1999 Fox GB, Levasseur RA, Faden AI: Behavioral responses of C57BL/6, FVB/N, and 129/SvEMS mouse strains to traumatic brain injury: implications for gene targeting approaches to neurotrauma. J Neurotrauma 16:377–389, 1999

    • Search Google Scholar
    • Export Citation
  • 23.

    Franklin KBJ, & Paxinos G: The Mouse Brain in Stereotaxic Coordinates. San Diego, CA: Academic Press, 1997 Franklin KBJ, Paxinos G: The Mouse Brain in Stereotaxic Coordinates. San Diego, CA: Academic Press, 1997

    • Search Google Scholar
    • Export Citation
  • 24.

    Geddes JF, , Vowles GH, & Nicoll JA, et al. : Neuronal cytoskeletal changes are an early consequence of repetitive head injury. Acta Neuropathol 98:171178, 1999 Geddes JF, Vowles GH, Nicoll JA, et al: Neuronal cytoskeletal changes are an early consequence of repetitive head injury. Acta Neuropathol 98:171–178, 1999

    • Search Google Scholar
    • Export Citation
  • 25.

    Geddes JF, , Vowles GH, & Robinson SF, et al. : Neurofibrillary tangles, but not Alzheimer-type pathology, in a young boxer. Neuropathol Appl Neurobiol 22:1216, 1996 Geddes JF, Vowles GH, Robinson SF, et al: Neurofibrillary tangles, but not Alzheimer-type pathology, in a young boxer. Neuropathol Appl Neurobiol 22:12–16, 1996

    • Search Google Scholar
    • Export Citation
  • 26.

    Gentleman SM, , Graham DI, & Roberts GW: Molecular pathology of head trauma: altered βAPP metabolism and the aetiology of Alzheimer's disease. Prog Brain Res 96:237246, 1993 Gentleman SM, Graham DI, Roberts GW: Molecular pathology of head trauma: altered βAPP metabolism and the aetiology of Alzheimer's disease. Prog Brain Res 96:237–246, 1993

    • Search Google Scholar
    • Export Citation
  • 27.

    Gervais FG, , Xu D, & Robertson GS, et al. : Involvement of caspases in proteolytic cleavage of Alzheimer's amyloid-beta precursor protein and amyloidogenic A beta peptide formation. Cell 97:395406, 1999 Gervais FG, Xu D, Robertson GS, et al: Involvement of caspases in proteolytic cleavage of Alzheimer's amyloid-beta precursor protein and amyloidogenic A beta peptide formation. Cell 97:395–406, 1999

    • Search Google Scholar
    • Export Citation
  • 28.

    Gordon WA, , Brown M, & Sliwinski M, et al. : The enigma of “hidden” traumatic brain injury. J Head Trauma Rehabil 13:3956, 1998 Gordon WA, Brown M, Sliwinski M, et al: The enigma of “hidden” traumatic brain injury. J Head Trauma Rehabil 13:39–56, 1998

    • Search Google Scholar
    • Export Citation
  • 29.

    Graves AB, , White E, & Koepsell TD, et al. : The association between head trauma and Alzheimer's disease. Am J Epidemiol 131:491501, 1990 Graves AB, White E, Koepsell TD, et al: The association between head trauma and Alzheimer's disease. Am J Epidemiol 131:491–501, 1990

    • Search Google Scholar
    • Export Citation
  • 30.

    Green GA, & Jordan SE: Are brain injuries a significant problem in soccer? Clin Sports Med 17:795809, 1998 Green GA, Jordan SE: Are brain injuries a significant problem in soccer? Clin Sports Med 17:795–809, 1998

    • Search Google Scholar
    • Export Citation
  • 31.

    Guskiewicz KM, , Riemann BL, & Perrin DH, et al. : Alternative approaches to the assessment of mild head injury in athletes. Med Sci Sports Exerc 29 (Suppl 7):S213S221, 1997 Guskiewicz KM, Riemann BL, Perrin DH, et al: Alternative approaches to the assessment of mild head injury in athletes. Med Sci Sports Exerc 29 (Suppl 7):S213–S221, 1997

    • Search Google Scholar
    • Export Citation
  • 32.

    Hamm RJ, , Dixon CE, & Gbadebo DM, et al. : Cognitive deficits following traumatic brain injury produced by controlled cortical impact. J Neurotrauma 9:1120, 1992 Hamm RJ, Dixon CE, Gbadebo DM, et al: Cognitive deficits following traumatic brain injury produced by controlled cortical impact. J Neurotrauma 9:11–20, 1992

    • Search Google Scholar
    • Export Citation
  • 33.

    Hamm RJ, , Pike BR, & O'Dell DM, et al. : The rotarod test: an evaluation of its effectiveness in assessing motor deficits following traumatic brain injury. J Neurotrauma 11:187196, 1994 Hamm RJ, Pike BR, O'Dell DM, et al: The rotarod test: an evaluation of its effectiveness in assessing motor deficits following traumatic brain injury. J Neurotrauma 11:187–196, 1994

    • Search Google Scholar
    • Export Citation
  • 34.

    Hicks RR, , Smith DH, & Lowenstein DH, et al. : Mild experimental brain injury in the rat induces cognitive deficits associated with regional neuronal loss in the hippocampus. J Neurotrauma 10:405414, 1993 Hicks RR, Smith DH, Lowenstein DH, et al: Mild experimental brain injury in the rat induces cognitive deficits associated with regional neuronal loss in the hippocampus. J Neurotrauma 10:405–414, 1993

    • Search Google Scholar
    • Export Citation
  • 35.

    Hogg S, , Moser PC, & Sanger DJ: Mild traumatic lesion of the right parietal cortex of the rat: selective behavioral deficits in the absence of neurological impairment. Behav Brain Res 93:143155, 1998 Hogg S, Moser PC, Sanger DJ: Mild traumatic lesion of the right parietal cortex of the rat: selective behavioral deficits in the absence of neurological impairment. Behav Brain Res 93:143–155, 1998

    • Search Google Scholar
    • Export Citation
  • 36.

    Hovda DA, , Becker DP, & Katayama Y: Secondary injury and acidosis. J Neurotrauma 9 (Suppl 1):S47S60, 1992 Hovda DA, Becker DP, Katayama Y: Secondary injury and acidosis. J Neurotrauma 9 (Suppl 1):S47–S60, 1992

    • Search Google Scholar
    • Export Citation
  • 37.

    Hovda DA, , Yoshino A, & Kawamata T, et al. : Diffuse prolonged depression of cerebral oxidative metabolism following concussive brain injury in the rat: a cytochrome oxidase histochemistry study. Brain Res 567:110, 1991 Hovda DA, Yoshino A, Kawamata T, et al: Diffuse prolonged depression of cerebral oxidative metabolism following concussive brain injury in the rat: a cytochrome oxidase histochemistry study. Brain Res 567:1–10, 1991

    • Search Google Scholar
    • Export Citation
  • 38.

    Hsiang JN, , Yeung T, & Yu AL, et al. : High-risk mild head injury. J Neurosurg 87:234238, 1997 Hsiang JN, Yeung T, Yu AL, et al: High-risk mild head injury. J Neurosurg 87:234–238, 1997

    • Search Google Scholar
    • Export Citation
  • 39.

    Ishihara T, , Hong M, & Zhang B, et al. : Age-dependent emergence and progression of a tauopathy in transgenic mice overexpressing the shortest human tau isoform. Neuron 24:751762, 1999 Ishihara T, Hong M, Zhang B, et al: Age-dependent emergence and progression of a tauopathy in transgenic mice overexpressing the shortest human tau isoform. Neuron 24:751–762, 1999

    • Search Google Scholar
    • Export Citation
  • 40.

    Jenkins LW, , Lu Y, & Johnston WE, et al. : Combined therapy affects outcomes differentially after mild traumatic brain injury and secondary forebrain ischemia in rats. Brain Res 817:132144, 1999 Jenkins LW, Lu Y, Johnston WE, et al: Combined therapy affects outcomes differentially after mild traumatic brain injury and secondary forebrain ischemia in rats. Brain Res 817:132–144, 1999

    • Search Google Scholar
    • Export Citation
  • 41.

    Jenkins LW, , Moszynski K, & Lyeth BG, et al. : Increased vulnerability of the mildly traumatized rat brain to cerebral ischemia: the use of controlled secondary ischemia as a research tool to identify common or different mechanisms contributing to mechanical and ischemic brain injury. Brain Res 477:211224, 1989 Jenkins LW, Moszynski K, Lyeth BG, et al: Increased vulnerability of the mildly traumatized rat brain to cerebral ischemia: the use of controlled secondary ischemia as a research tool to identify common or different mechanisms contributing to mechanical and ischemic brain injury. Brain Res 477:211–224, 1989

    • Search Google Scholar
    • Export Citation
  • 42.

    Johansson BB, & Ohlsson AL: Environment, social interaction, and physical activity as determinants of functional outcome after cerebral infarction in the rat. Exp Neurol 139:322327, 1996 Johansson BB, Ohlsson AL: Environment, social interaction, and physical activity as determinants of functional outcome after cerebral infarction in the rat. Exp Neurol 139:322–327, 1996

    • Search Google Scholar
    • Export Citation
  • 43.

    Jordan BD, , Relkin NR, & Ravdin LD, et al. : Apolipoprotein E ϵ4 associated with chronic traumatic brain injury in boxing. JAMA 278:136140, 1997 Jordan BD, Relkin NR, Ravdin LD, et al: Apolipoprotein E ϵ4 associated with chronic traumatic brain injury in boxing. JAMA 278:136–140, 1997

    • Search Google Scholar
    • Export Citation
  • 44.

    Jordan SE, , Green GA, & Galanty HL, et al. : Acute and chronic brain injury in United States National Team soccer players. Am J Sports Med 24:205210, 1996 Jordan SE, Green GA, Galanty HL, et al: Acute and chronic brain injury in United States National Team soccer players. Am J Sports Med 24:205–210, 1996

    • Search Google Scholar
    • Export Citation
  • 45.

    Kanayama G, , Takeda M, & Niigawa H, et al. : The effects of repetitive mild brain injury on cytoskeletal protein and behavior. Methods Find Exp Clin Pharmacol 18:105115, 1996 Kanayama G, Takeda M, Niigawa H, et al: The effects of repetitive mild brain injury on cytoskeletal protein and behavior. Methods Find Exp Clin Pharmacol 18:105–115, 1996

    • Search Google Scholar
    • Export Citation
  • 46.

    Kelly JP, , Nichols JS, & Filley CM, et al. : Concussion in sports. Guidelines for the prevention of catastrophic outcome. JAMA 266:28672869, 1991 Kelly JP, Nichols JS, Filley CM, et al: Concussion in sports. Guidelines for the prevention of catastrophic outcome. JAMA 266:2867–2869, 1991

    • Search Google Scholar
    • Export Citation
  • 47.

    Koelfen W, , Freund M, & Dinter D, et al. : Long-term follow up of children with head injuries-classified as “good recovery” using the Glasgow Outcome Scale: neurological, neuropsychological and magnetic resonance imaging results. Eur J Pediatr 156:230235, 1997 Koelfen W, Freund M, Dinter D, et al: Long-term follow up of children with head injuries-classified as “good recovery” using the Glasgow Outcome Scale: neurological, neuropsychological and magnetic resonance imaging results. Eur J Pediatr 156:230–235, 1997

    • Search Google Scholar
    • Export Citation
  • 48.

    Krege JH, , Hodgin JB, & Hagaman JR, et al. : A noninvasive computerized tail-cuff system for measuring blood pressure in mice. Hypertension 25:11111115, 1995 Krege JH, Hodgin JB, Hagaman JR, et al: A noninvasive computerized tail-cuff system for measuring blood pressure in mice. Hypertension 25:1111–1115, 1995

    • Search Google Scholar
    • Export Citation
  • 49.

    Lancon JA, , Haines DE, & Parent AD: Anatomy of the shaken baby syndrome. Anat Rec 253:1318, 1998 Lancon JA, Haines DE, Parent AD: Anatomy of the shaken baby syndrome. Anat Rec 253:13–18, 1998

    • Search Google Scholar
    • Export Citation
  • 50.

    Levin HS, , Mattis S, & Ruff RM, et al. : Neurobehavioral outcome following minor head injury: a three-center study. J Neurosurg 66:234243, 1987 Levin HS, Mattis S, Ruff RM, et al: Neurobehavioral outcome following minor head injury: a three-center study. J Neurosurg 66:234–243, 1987

    • Search Google Scholar
    • Export Citation
  • 51.

    Lewen A, , Li GL, & Olsson Y, et al. : Changes in microtubule-associated protein 2 and amyloid precursor protein immunoreactivity following traumatic brain injury in rat: influence of MK-801 treatment. Brain Res 719:161171, 1996 Lewen A, Li GL, Olsson Y, et al: Changes in microtubule-associated protein 2 and amyloid precursor protein immunoreactivity following traumatic brain injury in rat: influence of MK-801 treatment. Brain Res 719:161–171, 1996

    • Search Google Scholar
    • Export Citation
  • 52.

    Lowenstein DH, , Thomas MJ, & Smith DH, et al. : Selective vulnerability of dentate hilar neurons following traumatic brain injury: a potential mechanistic link between head trauma and disorders of the hippocampus. J Neurosci 12:48464853, 1992 Lowenstein DH, Thomas MJ, Smith DH, et al: Selective vulnerability of dentate hilar neurons following traumatic brain injury: a potential mechanistic link between head trauma and disorders of the hippocampus. J Neurosci 12:4846–4853, 1992

    • Search Google Scholar
    • Export Citation
  • 53.

    Lyeth BG, , Jenkins LW, & Hamm RJ, et al. : Prolonged memory impairment in the absence of hippocampal cell death following traumatic brain injury in the rat. Brain Res 526:249258, 1990 Lyeth BG, Jenkins LW, Hamm RJ, et al: Prolonged memory impairment in the absence of hippocampal cell death following traumatic brain injury in the rat. Brain Res 526:249–258, 1990

    • Search Google Scholar
    • Export Citation
  • 54.

    Marmarou A, , Foda MA, & van den Brink W, et al. : A new model of diffuse brain injury in rats. Part I: Pathophysiology and biomechanics. J Neurosurg 80:291300, 1994 Marmarou A, Foda MA, van den Brink W, et al: A new model of diffuse brain injury in rats. Part I: Pathophysiology and biomechanics. J Neurosurg 80:291–300, 1994

    • Search Google Scholar
    • Export Citation
  • 55.

    Masdeu JC, , Van Heertum RL, & Kleiman A, et al. : Early single-photon emission computed tomography in mild head trauma. A controlled study. J Neuroimaging 4:177181, 1994 Masdeu JC, Van Heertum RL, Kleiman A, et al: Early single-photon emission computed tomography in mild head trauma. A controlled study. J Neuroimaging 4:177–181, 1994

    • Search Google Scholar
    • Export Citation
  • 56.

    Matser EJ, , Kessels AG, & Lezak MD, et al. : Neuropsychological impairment in amateur soccer players. JAMA 282:971973, 1999 Matser EJ, Kessels AG, Lezak MD, et al: Neuropsychological impairment in amateur soccer players. JAMA 282:971–973, 1999

    • Search Google Scholar
    • Export Citation
  • 57.

    Matser JT, , Kessels AG, & Jordan BD, et al. : Chronic traumatic brain injury in professional soccer players. Neurology 51:791796, 1998 Matser JT, Kessels AG, Jordan BD, et al: Chronic traumatic brain injury in professional soccer players. Neurology 51:791–796, 1998

    • Search Google Scholar
    • Export Citation
  • 58.

    Mattiasson GJ, , Philips MF, & Tomasevic G, et al. : The rotating pole test: evaluation of its effectiveness in assessing functional motor deficits following experimental head injury in the rat. J Neurosci Methods 95:7582, 2000 Mattiasson GJ, Philips MF, Tomasevic G, et al: The rotating pole test: evaluation of its effectiveness in assessing functional motor deficits following experimental head injury in the rat. J Neurosci Methods 95:75–82, 2000

    • Search Google Scholar
    • Export Citation
  • 59.

    Maxwell WL, , Povlishock JT, & Graham DL: A mechanistic analysis of nondisruptive axonal injury: a review. J Neurotrauma 14:419440, 1997 Maxwell WL, Povlishock JT, Graham DL: A mechanistic analysis of nondisruptive axonal injury: a review. J Neurotrauma 14:419–440, 1997

    • Search Google Scholar
    • Export Citation
  • 60.

    McIntosh TK, , Noble L, & Andrews B, et al. : Traumatic brain injury in the rat: characterization of a midline fluid-percussion model. Cent Nerv Syst Trauma 4:119134, 1987 McIntosh TK, Noble L, Andrews B, et al: Traumatic brain injury in the rat: characterization of a midline fluid-percussion model. Cent Nerv Syst Trauma 4:119–134, 1987

    • Search Google Scholar
    • Export Citation
  • 61.

    McIntosh TK, , Vink R, & Noble L, et al. : Traumatic brain injury in the rat: characterization of a lateral fluid-percussion model. Neuroscience 28:233244, 1989 McIntosh TK, Vink R, Noble L, et al: Traumatic brain injury in the rat: characterization of a lateral fluid-percussion model. Neuroscience 28:233–244, 1989

    • Search Google Scholar
    • Export Citation
  • 62.

    Melvin JW, & Evans FG: A strain energy approach to the mechanics of skull fracture: 710871, in Backaitis SH (ed): Biomechanics of Impact Injury and Injury Tolerances of the Head-Neck Complex: PT-43. Warrendale, PA: SAE, 1993, pp 661680 Melvin JW, Evans FG: A strain energy approach to the mechanics of skull fracture: 710871, in Backaitis SH (ed): Biomechanics of Impact Injury and Injury Tolerances of the Head-Neck Complex: PT-43. Warrendale, PA: SAE, 1993, pp 661–680

    • Search Google Scholar
    • Export Citation
  • 63.

    Mills J, & Reiner PB: Regulation of amyloid precursor protein cleavage. J Neurochem 72:443460, 1999 Mills J, Reiner PB: Regulation of amyloid precursor protein cleavage. J Neurochem 72:443–460, 1999

    • Search Google Scholar
    • Export Citation
  • 64.

    Mittl RL, , Grossman RI, & Hiehle JF, et al. : Prevalence of MR evidence of diffuse axonal injury in patients with mild head injury and normal head CT findings. AJNR 15:15831589, 1994 Mittl RL, Grossman RI, Hiehle JF, et al: Prevalence of MR evidence of diffuse axonal injury in patients with mild head injury and normal head CT findings. AJNR 15:1583–1589, 1994

    • Search Google Scholar
    • Export Citation
  • 65.

    Morris RG, , Garrud P, & Rawlins JN, et al. : Place navigation impaired in rats with hippocampal lesions. Nature 297:681683, 1982 Morris RG, Garrud P, Rawlins JN, et al: Place navigation impaired in rats with hippocampal lesions. Nature 297:681–683, 1982

    • Search Google Scholar
    • Export Citation
  • 66.

    Murai H, , Pierce JE, & Raghupathi R, et al. : Twofold overexpression of human β-amyloid precursor proteins in transgenic mice does not affect the neuromotor, cognitive, or neurodegenerative sequelae following experimental brain injury. J Comp Neurol 392:428438, 1998 Murai H, Pierce JE, Raghupathi R, et al: Twofold overexpression of human β-amyloid precursor proteins in transgenic mice does not affect the neuromotor, cognitive, or neurodegenerative sequelae following experimental brain injury. J Comp Neurol 392:428–438, 1998

    • Search Google Scholar
    • Export Citation
  • 67.

    Nakamura M, , Raghupathi R, & Merry DE, et al. : Overexpression of Bcl-2 is neuroprotective after experimental brain injury in transgenic mice. J Comp Neurol 412:681692, 1999 Nakamura M, Raghupathi R, Merry DE, et al: Overexpression of Bcl-2 is neuroprotective after experimental brain injury in transgenic mice. J Comp Neurol 412:681–692, 1999

    • Search Google Scholar
    • Export Citation
  • 68.

    Nakamura M, , Saatman KE, & Galvin JE, et al. : Increased vulnerability of NFH-LacZ transgenic mouse to traumatic brain injury-induced behavioral deficits and cortical damage. J Cereb Blood Flow Metab 19:762770, 1999 Nakamura M, Saatman KE, Galvin JE, et al: Increased vulnerability of NFH-LacZ transgenic mouse to traumatic brain injury-induced behavioral deficits and cortical damage. J Cereb Blood Flow Metab 19:762–770, 1999

    • Search Google Scholar
    • Export Citation
  • 69.

    National Research Council: Guide for the Care and Use of Laboratory Animals. Washington, DC: National Academy Press, 1996 National Research Council: Guide for the Care and Use of Laboratory Animals. Washington, DC: National Academy Press, 1996

    • Search Google Scholar
    • Export Citation
  • 70.

    Nedd K, , Sfakianakis G, & Ganz W, et al. : 99mTc-HMPAO SPECT of the brain in mild to moderate traumatic brain injury patients: compared with CT—a prospective study. Brain Inj 7:469479, 1993 Nedd K, Sfakianakis G, Ganz W, et al: 99mTc-HMPAO SPECT of the brain in mild to moderate traumatic brain injury patients: compared with CT—a prospective study. Brain Inj 7:469–479, 1993

    • Search Google Scholar
    • Export Citation
  • 71.

    Newcombe F, , Rabbitt P, & Briggs M: Minor head injury: pathophysiological or iatrogenic sequelae? J Neurol Neurosurg Psychiatry 57:709716, 1994 Newcombe F, Rabbitt P, Briggs M: Minor head injury: pathophysiological or iatrogenic sequelae? J Neurol Neurosurg Psychiatry 57:709–716, 1994

    • Search Google Scholar
    • Export Citation
  • 72.

    Olsson Y, , Rinder L, & Lindgren S, et al. : Studies on vascular permeability changes in experimental brain concussion. 3. A comparison between the effects of single and repeated sudden mechanical loading of the brain. Acta Neuropathol 19:225233, 1971 Olsson Y, Rinder L, Lindgren S, et al: Studies on vascular permeability changes in experimental brain concussion. 3. A comparison between the effects of single and repeated sudden mechanical loading of the brain. Acta Neuropathol 19:225–233, 1971

    • Search Google Scholar
    • Export Citation
  • 73.

    O'Meara ES, , Kukull WA, & Sheppard L, et al. : Head injury and risk of Alzheimer's disease by apolipoprotein E genotype. Am J Epidemiol 146:373384, 1997 O'Meara ES, Kukull WA, Sheppard L, et al: Head injury and risk of Alzheimer's disease by apolipoprotein E genotype. Am J Epidemiol 146:373–384, 1997

    • Search Google Scholar
    • Export Citation
  • 74.

    Perez-Pinzon MA, , Alonso O, & Kraydieh S, et al. : Induction of tolerance against traumatic brain injury by ischemic preconditioning. Neuroreport 10:29512954, 1999 Perez-Pinzon MA, Alonso O, Kraydieh S, et al: Induction of tolerance against traumatic brain injury by ischemic preconditioning. Neuroreport 10:2951–2954, 1999

    • Search Google Scholar
    • Export Citation
  • 75.

    Pierce JE, , Smith DH, & Trojanowski JQ, et al. : Enduring cognitive, neurobehavioral and histopathological changes persist for up to one year following severe experimental brain injury in rats. Neuroscience 87:359369, 1998 Pierce JE, Smith DH, Trojanowski JQ, et al: Enduring cognitive, neurobehavioral and histopathological changes persist for up to one year following severe experimental brain injury in rats. Neuroscience 87:359–369, 1998

    • Search Google Scholar
    • Export Citation
  • 76.

    Pierce JE, , Trojanowski JQ, & Graham DI, et al. : Immunohistochemical characterization of alterations in the distribution of amyloid precursor proteins and β-amyloid peptide after experimental brain injury in the rat. J Neurosci 16:10831090, 1996 Pierce JE, Trojanowski JQ, Graham DI, et al: Immunohistochemical characterization of alterations in the distribution of amyloid precursor proteins and β-amyloid peptide after experimental brain injury in the rat. J Neurosci 16:1083–1090, 1996

    • Search Google Scholar
    • Export Citation
  • 77.

    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 69:171174, 1996 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

    • Search Google Scholar
    • Export Citation
  • 78.

    Raghupathi R, , Fernandez SC, & Murai H, et al. : BCL-2 overexpression attenuates cortical cell loss after traumatic brain injury in transgenic mice. J Cereb Blood Flow Metab 18:12591269, 1998 Raghupathi R, Fernandez SC, Murai H, et al: BCL-2 overexpression attenuates cortical cell loss after traumatic brain injury in transgenic mice. J Cereb Blood Flow Metab 18:1259–1269, 1998

    • Search Google Scholar
    • Export Citation
  • 79.

    Rimel RW, , Giordani B, & Barth JT, et al. : Moderate head injury: completing the clinical spectrum of brain trauma. Neurosurgery 11:344351, 1982 Rimel RW, Giordani B, Barth JT, et al: Moderate head injury: completing the clinical spectrum of brain trauma. Neurosurgery 11:344–351, 1982

    • Search Google Scholar
    • Export Citation
  • 80.

    Roberts GW, , Allsop D, & Bruton C: The occult aftermath of boxing. J Neurol Neurosurg Psychiatry 53:373378, 1990 Roberts GW, Allsop D, Bruton C: The occult aftermath of boxing. J Neurol Neurosurg Psychiatry 53:373–378, 1990

    • Search Google Scholar
    • Export Citation
  • 81.

    Roberts GW, , Whitwell HL, & Acland PR, et al. : Dementia in a punch drunk wife. Lancet 335:918919, 1990 Roberts GW, Whitwell HL, Acland PR, et al: Dementia in a punch drunk wife. Lancet 335:918–919, 1990

    • Search Google Scholar
    • Export Citation
  • 82.

    Saatman KE, , Graham DI, & McIntosh TK: The neuronal cytoskeleton is at risk after mild and moderate brain injury. J Neurotrauma 15:10471058, 1998 Saatman KE, Graham DI, McIntosh TK: The neuronal cytoskeleton is at risk after mild and moderate brain injury. J Neurotrauma 15:1047–1058, 1998

    • Search Google Scholar
    • Export Citation
  • 83.

    Samii A, , Badie H, & Fu K, et al. : Effects of an N-type calcium channel antagonist (SNX 111; Ziconotide) on calcium-45 accumulation following fluid-percussion injury. J Neurotrauma 16:879892, 1999 Samii A, Badie H, Fu K, et al: Effects of an N-type calcium channel antagonist (SNX 111; Ziconotide) on calcium-45 accumulation following fluid-percussion injury. J Neurotrauma 16:879–892, 1999

    • Search Google Scholar
    • Export Citation
  • 84.

    Scheff SW, , Baldwin SA, & Brown RW, et al. : Morris water maze deficits in rats following traumatic brain injury: lateral controlled cortical impact. J Neurotrauma 14:615627, 1997 Scheff SW, Baldwin SA, Brown RW, et al: Morris water maze deficits in rats following traumatic brain injury: lateral controlled cortical impact. J Neurotrauma 14:615–627, 1997

    • Search Google Scholar
    • Export Citation
  • 85.

    Scherbel U, , Raghupathi R, & Nakamura M, et al. : Differential acute and chronic responses of tumor necrosis factor-deficient mice to experimental brain injury. Proc Natl Acad Sci USA 96:87218726, 1999 Scherbel U, Raghupathi R, Nakamura M, et al: Differential acute and chronic responses of tumor necrosis factor-deficient mice to experimental brain injury. Proc Natl Acad Sci USA 96:8721–8726, 1999

    • Search Google Scholar
    • Export Citation
  • 86.

    Smith DH, , Chen XH, & Nonaka M, et al. : Accumulation of amyloid β and tau and the formation of neurofilament inclusions following diffuse brain injury in the pig. J Neuropathol Exp Neurol 58:982992, 1999 Smith DH, Chen XH, Nonaka M, et al: Accumulation of amyloid β and tau and the formation of neurofilament inclusions following diffuse brain injury in the pig. J Neuropathol Exp Neurol 58:982–992, 1999

    • Search Google Scholar
    • Export Citation
  • 87.

    Smith DH, , Nakamura M, & McIntosh TK, et al. : Brain trauma induces massive hippocampal neuron death linked to a surge in β-amyloid levels in mice overexpressing mutant amyloid precursor protein. Am J Pathol 153:10051010, 1998 Smith DH, Nakamura M, McIntosh TK, et al: Brain trauma induces massive hippocampal neuron death linked to a surge in β-amyloid levels in mice overexpressing mutant amyloid precursor protein. Am J Pathol 153:1005–1010, 1998

    • Search Google Scholar
    • Export Citation
  • 88.

    Smith DH, , Soares HD, & Pierce JS, et al. : A model of parasagittal controlled cortical impact in the mouse: cognitive and histopathologic effects. J Neurotrauma 12:169178, 1995 Smith DH, Soares HD, Pierce JS, et al: A model of parasagittal controlled cortical impact in the mouse: cognitive and histopathologic effects. J Neurotrauma 12:169–178, 1995

    • Search Google Scholar
    • Export Citation
  • 89.

    Stagliano NE, , Perez-Pinzon MA, & Moskowitz MA, et al. : Focal ischemic preconditioning induces rapid tolerance to middle cerebral artery occlusion in mice. J Cereb Blood Flow Metab 19:757761, 1999 Stagliano NE, Perez-Pinzon MA, Moskowitz MA, et al: Focal ischemic preconditioning induces rapid tolerance to middle cerebral artery occlusion in mice. J Cereb Blood Flow Metab 19:757–761, 1999

    • Search Google Scholar
    • Export Citation
  • 90.

    Strugar J, , Sass KJ, & Buchanan CP, et al. : Long-term consequences of minimal brain injury: loss of consciousness does not predict memory impairment. J Trauma 34:555559, 1993 Strugar J, Sass KJ, Buchanan CP, et al: Long-term consequences of minimal brain injury: loss of consciousness does not predict memory impairment. J Trauma 34:555–559, 1993

    • Search Google Scholar
    • Export Citation
  • 91.

    Tang YP, , Noda Y, & Hasegawa T, et al. : A concussive-like brain injury model in mice (I): impairment in learning and memory. J Neurotrauma 14:851862, 1997 Tang YP, Noda Y, Hasegawa T, et al: A concussive-like brain injury model in mice (I): impairment in learning and memory. J Neurotrauma 14:851–862, 1997

    • Search Google Scholar
    • Export Citation
  • 92.

    Tang YP, , Noda Y, & Hasegawa T, et al. : A concussive-like brain injury model in mice (II): selective neuronal loss in the cortex and hippocampus. J Neurotrauma 14:863873, 1997 Tang YP, Noda Y, Hasegawa T, et al: A concussive-like brain injury model in mice (II): selective neuronal loss in the cortex and hippocampus. J Neurotrauma 14:863–873, 1997

    • Search Google Scholar
    • Export Citation
  • 93.

    Tanno H, , Nockels RP, & Pitts LH, et al. : Breakdown of the blood-brain barrier after fluid percussive brain injury in the rat. Part 1: Distribution and time course of protein extravasation. J Neurotrauma 9:2132, 1992 Tanno H, Nockels RP, Pitts LH, et al: Breakdown of the blood-brain barrier after fluid percussive brain injury in the rat. Part 1: Distribution and time course of protein extravasation. J Neurotrauma 9:21–32, 1992

    • Search Google Scholar
    • Export Citation
  • 94.

    Tokutomi T, , Hirohata M, & Miyagi T, et al. : Posttraumatic edema in the corpus callosum shown by MRI. Acta Neurochir Suppl 70:8083, 1997 Tokutomi T, Hirohata M, Miyagi T, et al: Posttraumatic edema in the corpus callosum shown by MRI. Acta Neurochir Suppl 70:80–83, 1997

    • Search Google Scholar
    • Export Citation
  • 95.

    Tysvaer AT, , Storli OV, & Bachen NI: Soccer injuries to the brain. A neurologic and electroencephalographic study of former players. Acta Neurol Scand 80:151156, 1989 Tysvaer AT, Storli OV, Bachen NI: Soccer injuries to the brain. A neurologic and electroencephalographic study of former players. Acta Neurol Scand 80:151–156, 1989

    • Search Google Scholar
    • Export Citation
  • 96.

    Waxweiler RJ, , Thurman D, & Sniezek J, et al. : Monitoring the impact of traumatic brain injury: a review and update. J Neurotrauma 12:509516, 1995 Waxweiler RJ, Thurman D, Sniezek J, et al: Monitoring the impact of traumatic brain injury: a review and update. J Neurotrauma 12:509–516, 1995

    • Search Google Scholar
    • Export Citation
  • 97.

    Yoshino A, , Hovda DA, & Kawamata T, et al. : Dynamic changes in local cerebral glucose utilization following cerebral conclusion in rats: evidence of a hyper- and subsequent hypometabolic state. Brain Res 561:106119, 1991 Yoshino A, Hovda DA, Kawamata T, et al: Dynamic changes in local cerebral glucose utilization following cerebral conclusion in rats: evidence of a hyper- and subsequent hypometabolic state. Brain Res 561:106–119, 1991

    • Search Google Scholar
    • Export Citation
  • 98.

    Zhang C, , Raghupathi R, & Saatman KE, et al. : Riluzole attenuates cortical lesion size, but not hippocampal neuronal loss, following traumatic brain injury in the rat. J Neurosci Res 52:342349, 1998 Zhang C, Raghupathi R, Saatman KE, et al: Riluzole attenuates cortical lesion size, but not hippocampal neuronal loss, following traumatic brain injury in the rat. J Neurosci Res 52:342–349, 1998

    • Search Google Scholar
    • Export Citation

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