A new model of diffuse brain injury in rats

Part I: Pathophysiology and biomechanics

Restricted access

✓ This report describes the development of an experimental head injury model capable of producing diffuse brain injury in the rodent. A total of 161 anesthetized adult rats were injured utilizing a simple weight-drop device consisting of a segmented brass weight free-falling through a Plexiglas guide tube. Skull fracture was prevented by cementing a small stainless-steel disc on the calvaria. Two groups of rats were tested: Group 1, consisting of 54 rats, to establish fracture threshold; and Group 2, consisting of 107 animals, to determine the primary cause of death at severe injury levels. Data from Group 1 animals showed that a 450-gm weight falling from a 2-m height (0.9 kg-m) resulted in a mortality rate of 44% with a low incidence (12.5%) of skull fracture. Impact was followed by apnea, convulsions, and moderate hypertension. The surviving rats developed decortication flexion deformity of the forelimbs, with behavioral depression and loss of muscle tone. Data from Group 2 animals suggested that the cause of death was due to central respiratory depression; the mortality rate decreased markedly in animals mechanically ventilated during the impact. Analysis of mathematical models showed that this mass-height combination resulted in a brain acceleration of 900 G and a brain compression gradient of 0.28 mm. It is concluded that this simple model is capable of producing a graded brain injury in the rodent without a massive hypertensive surge or excessive brain-stem damage.

Article Information

Contributor Notes

Address reprint requests to: Anthony Marmarou, Ph.D., Division of Neurosurgery, Medical College of Virginia, Box 508, MCV Station, Richmond, Virginia 23298.
Headings
References
  • 1.

    Adams JHDoyle DFord Iet al: Diffuse axonal injury in head injury: definition, diagnosis and grading. Histopathology 15:49591989Adams JH Doyle D Ford I et al: Diffuse axonal injury in head injury: definition diagnosis and grading. Histopathology 15:49–59 1989

    • Search Google Scholar
    • Export Citation
  • 2.

    Bakay LLee JCLee GCet al: Experimental cerebral concussion. Part 1: An electron microscopic study. J Neurosurg 47:5255311977Bakay L Lee JC Lee GC et al: Experimental cerebral concussion. Part 1: An electron microscopic study. J Neurosurg 47:525–531 1977

    • Search Google Scholar
    • Export Citation
  • 3.

    Beckman DLBean JW: Pulmonary damage and head injury. Proc Soc Exp Biol Med 130:591969Beckman DL Bean JW: Pulmonary damage and head injury. Proc Soc Exp Biol Med 130:5–9 1969

    • Search Google Scholar
    • Export Citation
  • 4.

    Dixon CELyeth BGPovlishock JTet al: A fluid percussion model of experimental brain injury in the rat. J Neurosurg 67:1101191987Dixon CE Lyeth BG Povlishock JT et al: A fluid percussion model of experimental brain injury in the rat. J Neurosurg 67:110–119 1987

    • Search Google Scholar
    • Export Citation
  • 5.

    Foda MAAMarmarou A: A new model of diffuse brain injury in rats. Part II: Morphological characterization. J Neurosurg 80:3013131994Foda MAA Marmarou A: A new model of diffuse brain injury in rats. Part II: Morphological characterization. J Neurosurg 80:301–313 1994

    • Search Google Scholar
    • Export Citation
  • 6.

    Gennarelli TAThibault LE: Biological models of head injury in Becker DPPovlishock JT (eds): Central Nervous System Trauma Status Report. Bethesda, Md: National Institutes of Health1985 pp 391404Gennarelli TA Thibault LE: Biological models of head injury in Becker DP Povlishock JT (eds): Central Nervous System Trauma Status Report. Bethesda Md: National Institutes of Health 1985 pp 391–404

    • Search Google Scholar
    • Export Citation
  • 7.

    Gennarelli TAThibault LEAdams JHet al: Diffuse axonal injury and traumatic coma in the primate. Ann Neurol 12:5645741982Gennarelli TA Thibault LE Adams JH et al: Diffuse axonal injury and traumatic coma in the primate. Ann Neurol 12: 564–574 1982

    • Search Google Scholar
    • Export Citation
  • 8.

    Gennarelli TAThibault LEOmmaya AK: Pathophysiologic responses to rotational and translational accelerations of the head in Proceedings of the 16th Strapp Car Crash Conference. New York: Society of Automobile Engineers1972 pp 295308Gennarelli TA Thibault LE Ommaya AK: Pathophysiologic responses to rotational and translational accelerations of the head in Proceedings of the 16th Strapp Car Crash Conference. New York: Society of Automobile Engineers 1972 pp 295–308

    • Search Google Scholar
    • Export Citation
  • 9.

    Grubb RL JrNaumann RAOmmaya AK: Respiration and the cerebrospinal fluid in experimental cerebral concussion. J Neurosurg 32:3203291970Grubb RL Jr Naumann RA Ommaya AK: Respiration and the cerebrospinal fluid in experimental cerebral concussion. J Neurosurg 32:320–329 1970

    • Search Google Scholar
    • Export Citation
  • 10.

    Hawkins TDLloyd ADFletcher GICet al: Ventricular size following head injury: a clinicoradiological study. Clin Radiol 27:2792891976Hawkins TD Lloyd AD Fletcher GIC et al: Ventricular size following head injury: a clinicoradiological study. Clin Radiol 27:279–289 1976

    • Search Google Scholar
    • Export Citation
  • 11.

    Huger FPatrick G: Effect of concussive head injury on central catecholamine levels and synthesis rates in rat brain regions. J Neurochem 33:89951979Huger F Patrick G: Effect of concussive head injury on central catecholamine levels and synthesis rates in rat brain regions. J Neurochem 33:89–95 1979

    • Search Google Scholar
    • Export Citation
  • 12.

    Levin HSMeyers CAGrossman RGet al: Ventricular enlargement after closed head injury. Arch Neurol 38:6236291981Levin HS Meyers CA Grossman RG et al: Ventricular enlargement after closed head injury. Arch Neurol 38:623–629 1981

    • Search Google Scholar
    • Export Citation
  • 13.

    Lewelt WJenkins LWMiller JD: Autoregulation of cerebral blood flow after experimental fluid percussion injury of the brain. J Neurosurg 53:5005111980Lewelt W Jenkins LW Miller JD: Autoregulation of cerebral blood flow after experimental fluid percussion injury of the brain. J Neurosurg 53:500–511 1980

    • Search Google Scholar
    • Export Citation
  • 14.

    Marshall LFMarshall SBKlauber MRet al: A new classification of head injury based on computerized tomography. J Neurosurg 75:S14S201991Marshall LF Marshall SB Klauber MR et al: A new classification of head injury based on computerized tomography. J Neurosurg 75:S14–S20 1991

    • Search Google Scholar
    • Export Citation
  • 15.

    McIntosh TKVink RNoble Let al: Traumatic brain injury in the rat: characterization of a lateral fluid-percussion model. Neuroscience 28:2332441989McIntosh 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
  • 16.

    Meyer SJKondo ANomura Fet al: Cerebral hemodynamics and metabolism following experimental head injury. J Neurosurg 32:3043191970Meyer SJ Kondo A Nomura F et al: Cerebral hemodynamics and metabolism following experimental head injury. J Neurosurg 32:304–319 1970

    • Search Google Scholar
    • Export Citation
  • 17.

    Millen JEGlauser FLZimmerman M: Physiological effects of controlled concussive brain trauma. J Appl Physiol 49:8568621980Millen JE Glauser FL Zimmerman M: Physiological effects of controlled concussive brain trauma. J Appl Physiol 49:856–862 1980

    • Search Google Scholar
    • Export Citation
  • 18.

    Nelson SRLowry OHPassonneau JV: Changes in energy reserves in mouse brain associated with compressive head injury in Caveness WFWalker AE (eds): Head Injury. Conference Proceedings. Philadelphia: JB Lippincott1966 pp 444447Nelson SR Lowry OH Passonneau JV: Changes in energy reserves in mouse brain associated with compressive head injury in Caveness WF Walker AE (eds): Head Injury. Conference Proceedings. Philadelphia: JB Lippincott 1966 pp 444–447

    • Search Google Scholar
    • Export Citation
  • 19.

    Nilsson BNordström CH: Experimental head injury in the rat. Part 3: Cerebral blood flow and oxygen consumption after concussive impact acceleration. J Neurosurg 47:2622731977Nilsson B Nordström CH: Experimental head injury in the rat. Part 3: Cerebral blood flow and oxygen consumption after concussive impact acceleration. J Neurosurg 47:262–273 1977

    • Search Google Scholar
    • Export Citation
  • 20.

    Nilsson BNordström CH: Rate of cerebral energy consumption in concussive head injury in the rat. J Neurosurg 47:2742811977Nilsson B Nordström CH: Rate of cerebral energy consumption in concussive head injury in the rat. J Neurosurg 47:274–281 1977

    • Search Google Scholar
    • Export Citation
  • 21.

    Nilsson BPontén U: Experimental head injury in the rat. Part 2: Regional brain energy metabolism in concussive trauma. J Neurosurg 47:2522611977Nilsson B Pontén U: Experimental head injury in the rat. Part 2: Regional brain energy metabolism in concussive trauma. J Neurosurg 47:252–261 1977

    • Search Google Scholar
    • Export Citation
  • 22.

    Nilsson BPontén UVoigt G: Experimental head injury in the rat. Part 1: Mechanics, pathophysiology, and morphology in an impact acceleration trauma model. J Neurosurg 47:2412511977Nilsson B Pontén 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

    • Search Google Scholar
    • Export Citation
  • 23.

    Ommaya AKGennarelli TA: Cerebral concussion and traumatic unconsciousness. Correlation of experimental and clinical observation on blunt head injuries. Brain 97:6336541974Ommaya AK Gennarelli TA: Cerebral concussion and traumatic unconsciousness. Correlation of experimental and clinical observation on blunt head injuries. Brain 97:633–654 1974

    • Search Google Scholar
    • Export Citation
  • 24.

    Ommaya AKGennarelli TA: Correlation between the biomechanics and pathophysiology of head injury in Sano KIshii S (eds): Neural Trauma. New York: American Elsevier1974 pp 275289Ommaya AK Gennarelli TA: Correlation between the biomechanics and pathophysiology of head injury in Sano K Ishii S (eds): Neural Trauma. New York: American Elsevier 1974 pp 275–289

    • Search Google Scholar
    • Export Citation
  • 25.

    Shapira YShohami ESidi Aet al: Experimental closed head injury in rats: mechanical, pathophysiologic, and neurologic properties. Crit Care Med 16:2582651988Shapira Y Shohami E Sidi A et al: Experimental closed head injury in rats: mechanical pathophysiologic and neurologic properties. Crit Care Med 16:258–265 1988

    • Search Google Scholar
    • Export Citation
  • 26.

    Shima KMarmarou A: Evaluation of brain-stem dysfunction following severe fluid-percussion head injury to the cat. J Neurosurg 74:2702771991Shima K Marmarou A: Evaluation of brain-stem dysfunction following severe fluid-percussion head injury to the cat. J Neurosurg 74:270–277 1991

    • Search Google Scholar
    • Export Citation
  • 27.

    Sullivan HGMartinez JBecker DPet al: Fluid-percussion model of mechanical brain injury in the cat. J Neurosurg 45:5205341976Sullivan HG Martinez J Becker DP et al: Fluid-percussion model of mechanical brain injury in the cat. J Neurosurg 45:520–534 1976

    • Search Google Scholar
    • Export Citation
  • 28.

    van den Brink WSlomka WMarmarou Aet al: Neurophysiological evidence of preservation of brain stem function in a new model of closed head injury in the rat in Avezaat Cvan Eijndhoven JMaas Aet al (eds): Intracranial Pressure VII. Berlin: Springer-Verlag1993 pp 221226van den Brink W Slomka W Marmarou A et al: Neurophysiological evidence of preservation of brain stem function in a new model of closed head injury in the rat in Avezaat C van Eijndhoven J Maas A et al (eds): Intracranial Pressure VII. Berlin: Springer-Verlag 1993 pp 221–226

    • Search Google Scholar
    • Export Citation
  • 29.

    van Dongen KJBraakman R: Late computed tomography in survivors of severe head injury. Neurosurgery 7:14221980van Dongen KJ Braakman R: Late computed tomography in survivors of severe head injury. Neurosurgery 7:14–22 1980

    • Search Google Scholar
    • Export Citation
  • 30.

    West MParkinson DHavlicek V: Spectral analysis of the electroencephalographic response to experimental concussion in the rat. Electroencephalogr Clin Neurophysiol 53:1922001982West M Parkinson D Havlicek V: Spectral analysis of the electroencephalographic response to experimental concussion in the rat. Electroencephalogr Clin Neurophysiol 53:192–200 1982

    • Search Google Scholar
    • Export Citation
  • 31.

    Yuan X-QWade CClifford C: Immediate hypertensive response to fluid percussion brain injury may be related to intraccrebral hemorrhage and hypothalamic damage. J Neurotrauma 8:2192281991Yuan X-Q Wade C Clifford C: Immediate hypertensive response to fluid percussion brain injury may be related to intraccrebral hemorrhage and hypothalamic damage. J Neurotrauma 8:219–228 1991

    • Search Google Scholar
    • Export Citation
TrendMD
Cited By
Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 1532 1155 78
Full Text Views 561 176 12
PDF Downloads 382 115 7
EPUB Downloads 0 0 0
PubMed
Google Scholar