A fluid percussion model of experimental brain injury in the rat

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✓ Fluid percussion models produce brain injury by rapidly injecting fluid volumes into the cranial cavity. The authors have systematically examined the effects of varying magnitudes of fluid percussion injury in the rat on neurological, systemic physiological, and histopathological changes. Acute neurological experiments showed that fluid percussion injury in 53 rats produced either irreversible apnea and death or transient apnea (lasting 54 seconds or less) and reversible suppression of postural and nonpostural function (lasting 60 minutes or less). As the magnitude if injury increased, the mortality rate and the duration of suppression of somatomotor reflexes increased. Unlike other rat models in which concussive brain injury is produced by impact, convulsions were observed in only 13% of survivors. Transient apnea was probably not associated with a significant hypoxic insult to animals that survived. Ten rats that sustained a moderate magnitude of injury (2.9 atm) exhibited chronic locomotor deficits that persisted for 4 to 8 days. Systemic physiological experiments in 20 rats demonstrated that all levels of injury studied produced acute systemic hypertension, bradycardia, and increased plasma glucose levels. Hypertension with subsequent hypotension resulted from higher magnitudes of injury. The durations of hypertension and suppression of amplitude on electroencephalography were related to the magnitudes of injury. While low levels of injury produced no significant histopathological alterations, higher magnitudes produced subarachnoid and intraparenchymal hemorrhage and, with increasing survival, necrotic change and cavitation. These data demonstrate that fluid percussion injury in the rat reproduces many of the features of head injury observed in other models and species. Thus, this animal model could represent a useful experimental approach to studies of pathological changes similar to those seen in human head injury.

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Address reprint requests to: C. Edward Dixon, Ph.D., Division of Neurosurgery, P.O. Box 693, MCV Station, Richmond, Virginia 23298.

© AANS, except where prohibited by US copyright law.

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Figures

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    Diagram of the fluid-percussion model of brain injury in the rat. A 4-mm central craniectomy is connected to one end of a Plexiglas cylinder filled with physiological saline. At the other end in the cylinder is a Plexiglas cork mounted on O-rings. Injury is produced by striking the cork with a 4.8-kg pendulum dropped from a specific height. The pressure transient is recorded on a storage oscilloscope with an extracranial transducer.

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    Effects of varying magnitudes of fluid percussion injury on acute neurological functioning. The data present mean durations of suppression ± standard error of the mean of: A) simple nonpostural reflexes; B) simple postural reflexes; C) complex nonpostural reflexes; D) complex postural responses; and E) complex locomotor responses.

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    Chronic changes in beam-balancing and beam-walking performance, and in body weight following a 2.9-atm fluid percussion injury. Data are plotted over 10 days from the time of injury for 10 rats. Asterisks: p < 0.05 versus baseline (Duncan's multiple-range test).

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    Mean arterial blood pressure ± standard error of the mean in traumatized rats following varying magnitudes of fluid percussion injury and in the sham-treated control group. Data are plotted over 60 minutes from the time of injury.

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    Example of the electroencephalographic (EEG) changes recorded from a single rat injured at 2.9 atm. Tracings were obtained preinjury (A), immediately postinjury (B, arrow indicates time of injury), and at 45 minutes postinjury (C) showing recovery of the EEG amplitude.

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    Photomicrographs of brain sections cut in a sagittal plane illustrating the alterations seen immediately after injury in the range of 2.9 to 3.6 atm. In the cerebrum (left) hemorrhage is readily seen in the corpus callosum, fimbria hippocampi, and thalamus, whereas the brain stem (right) reveals only scattered petechial hemorrhages confined to the ventral midline. H & E, × 12 (left), × 13 (right).

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    Photomicrographs of brain sections cut sagittally showing typical alterations seen immediately after a 3.8-atm injury. Intraparenchymal hemorrhage within the cerebrum (left), although more extensive than in the animals receiving less severe injuries, is still confined to the corpus callosum, the cortical gray/white matter interface, and the fimbria hippocampi. The brain stem (right) reveals extensive intraparenchymal hemorrhage confined to the midline of the pontomesencephalic and cervicomedullary junctions, while the cerebellum also shows hemorrhagic focci. H & E, × 10.

References

1.

Annegers JFGrabow JDGroover RVet al: Seizures after head trauma: a population study. Neurology 30:6836891980Annegers JF Grabow JD Groover RV et al: Seizures after head trauma: a population study. Neurology 30:683–689 1980

2.

Baker HLindsey JWeisbroth S: Selected normative data in Baker HJLindsey JRWeisbroth SH (eds): The Laboratory Rat. New York: Academic Press1979 Vol 1 pp 411412Baker H Lindsey J Weisbroth S: Selected normative data in Baker HJ Lindsey JR Weisbroth SH (eds): The Laboratory Rat. New York: Academic Press 1979 Vol 1 pp 411–412

3.

Beckman DL: Pulmonary responses to experimental brain injury in Becker DPPovlishock JT (eds): Central Nervous System Status Report 1985. Bethesda, Md: National Institute of Neurological and Communicative Disorders and Stroke1985 pp 417424Beckman DL: Pulmonary responses to experimental brain injury in Becker DP Povlishock JT (eds): Central Nervous System Status Report 1985. Bethesda Md: National Institute of Neurological and Communicative Disorders and Stroke 1985 pp 417–424

4.

Bederson JBBartkowski HMMoon Ket al: Nuclear magnetic resonance imaging and spectroscopy in experimental brain edema in a rat model. J Neurosurg 64:7958021986Bederson JB Bartkowski HM Moon K et al: Nuclear magnetic resonance imaging and spectroscopy in experimental brain edema in a rat model. J Neurosurg 64:795–802 1986

5.

Blomqvist PWieloch T: Ischemic brain damage in rats following cardiac arrest using a long-term recovery model. J Cereb Blood Flow Metab 5:4204311985Blomqvist P Wieloch T: Ischemic brain damage in rats following cardiac arrest using a long-term recovery model. J Cereb Blood Flow Metab 5:420–431 1985

6.

Bruce DALangfitt TWMiller JDet al: Regional cerebral blood flow, intracranial pressure, and brain metabolism in comatose patients. J Neurosurg 38:1311441973Bruce DA Langfitt TW Miller JD et al: Regional cerebral blood flow intracranial pressure and brain metabolism in comatose patients. J Neurosurg 38:131–144 1973

7.

Cheney DLTrabucchi MRacagni Get al: Effects of acute and chronic morphine on regional rat brain acetylcholine turnover rate. Life Sci 15:197719901974Cheney DL Trabucchi M Racagni G et al: Effects of acute and chronic morphine on regional rat brain acetylcholine turnover rate. Life Sci 15:1977–1990 1974

8.

Collier HOJ: Multiple toe-pinch test for potential analgesic drugs in Keele CASmith R (eds): The Assessment of Pain in Man and Animals. London: Universities Federation for Animal Welfare1962 pp 262270Collier HOJ: Multiple toe-pinch test for potential analgesic drugs in Keele CA Smith R (eds): The Assessment of Pain in Man and Animals. London: Universities Federation for Animal Welfare 1962 pp 262–270

9.

Denny-Brown DRussell WR: Experimental cerebral concussion. Brain 64:931641941Denny-Brown D Russell WR: Experimental cerebral concussion. Brain 64:93–164 1941

10.

Feeney DMGonzalez ALaw WA: Amphetamine, haloperidol, and experience interact to affect rate of recovery after motor cortex injury. Science 217:8558571982Feeney DM Gonzalez A Law WA: Amphetamine haloperidol and experience interact to affect rate of recovery after motor cortex injury. Science 217:855–857 1982

11.

Fukuda HTanaka TKaijima Met al: Quisqualic acid-induced hippocampal seizures in unanesthetized cats. Neurosci Lett 59:53591985Fukuda H Tanaka T Kaijima M et al: Quisqualic acid-induced hippocampal seizures in unanesthetized cats. Neurosci Lett 59:53–59 1985

12.

Gennarelli TAThibault LE: Biological models of head injury in Becker DPPovlishock JT (eds): Central Nervous System Trauma Status Report 1985. Bethesda, Md: National Institute of Neurological and Communicative Disorders and Stroke1985 pp 391404Gennarelli TA Thibault LE: Biological models of head injury in Becker DP Povlishock JT (eds): Central Nervous System Trauma Status Report 1985. Bethesda Md: National Institute of Neurological and Communicative Disorders and Stroke 1985 pp 391–404

13.

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

14.

Govons SRGovons RBVanHuss WDet al: Brain concussion in the rat. Exp Neurol 34:1211281972Govons SR Govons RB VanHuss WD et al: Brain concussion in the rat. Exp Neurol 34:121–128 1972

15.

Gurdjian ESLissner HRWebster JEet al: Studies on experimental concussion. Relation of physiologic effect to time duration of intracranial pressure increase at impact. Neurology 4:6746811954Gurdjian ES Lissner HR Webster JE et al: Studies on experimental concussion. Relation of physiologic effect to time duration of intracranial pressure increase at impact. Neurology 4:674–681 1954

16.

Hayes RLLewelt WYeatts MLet al: Metabolic behavioral and electrophysiological correlates of experimental brain injury in the cat. J Cereb Blood Flow Metab 3 (Suppl 1):S39S401983Hayes RL Lewelt W Yeatts ML et al: Metabolic behavioral and electrophysiological correlates of experimental brain injury in the cat. J Cereb Blood Flow Metab 3 (Suppl 1):S39–S40 1983

17.

Hayes RLStalhammer DAGalinat BJet al: A new model of concussive brain injury in the cat produced by extradural fluid volume loading. II. Physiological and neuropathological observations. Brain Injury (In press1987)Hayes RL Stalhammer DA Galinat BJ et al: A new model of concussive brain injury in the cat produced by extradural fluid volume loading. II. Physiological and neuropathological observations. Brain Injury (In press 1987)

18.

Ishige NPitts LHHashimoto Tet al: The effect of hypoxia on traumatic brain injury in rats. Part 1. Changes in neurological function, electroencephalogram, and histopathology. Neurosurgery (In press1987)Ishige N Pitts LH Hashimoto T et al: The effect of hypoxia on traumatic brain injury in rats. Part 1. Changes in neurological function electroencephalogram and histopathology. Neurosurgery (In press 1987)

19.

Jennett BSnoek JBond MRet al: Disability after severe head injury: observations on the use of the Glasgow Coma Scale. J Neurol Neurosurg Psychiatry 44:2852931981Jennett B Snoek J Bond MR et al: Disability after severe head injury: observations on the use of the Glasgow Coma Scale. J Neurol Neurosurg Psychiatry 44:285–293 1981

20.

Katayama YYoung HFDunbar JGet al: Coma associated with flaccidity produced by fluid percussion head injury in the cat. Part 2: contribution of activity in the pontine inhibitory system. Brain Injury (In press1987)Katayama Y Young HF Dunbar JG et al: Coma associated with flaccidity produced by fluid percussion head injury in the cat. Part 2: contribution of activity in the pontine inhibitory system. Brain Injury (In press 1987)

21.

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

22.

Lindgren SRinder L: Experimental studies in head injury. II. Pressure propagation in “percussion concussion.” Biophysik 3:1741801966Lindgren S Rinder L: Experimental studies in head injury. II. Pressure propagation in “percussion concussion.” Biophysik 3:174–180 1966

23.

Lyeth BGDixon CEHamm RJet al: Neurological deficits following experimental cerebral concussion in the rat attenuated by scopolamine pretreatment. Soc Neurosci Abst 11:4321985 (Abstract)Lyeth BG Dixon CE Hamm RJ et al: Neurological deficits following experimental cerebral concussion in the rat attenuated by scopolamine pretreatment. Soc Neurosci Abst 11:432 1985 (Abstract)

24.

Millen JEGlauser FL: Low levels of concussive brain trauma and pulmonary edema. J Appl Physiol 54:6666701983Millen JE Glauser FL: Low levels of concussive brain trauma and pulmonary edema. J Appl Physiol 54:666–670 1983

25.

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

26.

Ommaya AKGeller AParsons LC: The effects of experimental head injury on one-trial learning in rats. Int J Neurosci 1:3713781971Ommaya AK Geller A Parsons LC: The effects of experimental head injury on one-trial learning in rats. Int J Neurosci 1:371–378 1971

27.

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

28.

Parkinson DWest MPathiraja T: Concussion: comparisons of humans and rats. Neurosurgery 3:1761801978Parkinson D West M Pathiraja T: Concussion: comparisons of humans and rats. Neurosurgery 3:176–180 1978

29.

Povlishock JT: The morphopathologic responses to experimental head injuries of varying severity in Becker DPPovlishock JT (eds): Central Nervous System Trauma Status Report 1985. Bethesda, Md: National Institute of Neurological and Communicative Disorders and Stroke1985 pp 443452Povlishock JT: The morphopathologic responses to experimental head injuries of varying severity in Becker DP Povlishock JT (eds): Central Nervous System Trauma Status Report 1985. Bethesda Md: National Institute of Neurological and Communicative Disorders and Stroke 1985 pp 443–452

30.

Povlishock JTBecker DPSullivan HGet al: Vascular permeability alterations to horseradish peroxidase in experimental brain injury. Brain Res 153:2232391978Povlishock JT Becker DP Sullivan HG et al: Vascular permeability alterations to horseradish peroxidase in experimental brain injury. Brain Res 153:223–239 1978

31.

Racagni GCheney DLTrabucchi Met al: Measurement of acetylcholine turnover rate in discrete areas of rat brain. Life Sci 15:196119751974Racagni G Cheney DL Trabucchi M et al: Measurement of acetylcholine turnover rate in discrete areas of rat brain. Life Sci 15:1961–1975 1974

32.

Rosner MJ: Systemic response to experimental head injury in Becker DPPovlishock JT (eds): Central Nervous System Trauma Status Report 1985. Bethesda, Md: National Institute of Neurological and Communicative Disorders and Stroke1985 pp 405415Rosner MJ: Systemic response to experimental head injury in Becker DP Povlishock JT (eds): Central Nervous System Trauma Status Report 1985. Bethesda Md: National Institute of Neurological and Communicative Disorders and Stroke 1985 pp 405–415

33.

Rosner MJBecker DP: The etiology of plateau waves: a theoretical model and experimental observations in Ishii SNagai HBrock M (eds): Intracranial Pressure V. Berlin: Springer-Verlag1983 pp 301306Rosner MJ Becker DP: The etiology of plateau waves: a theoretical model and experimental observations in Ishii S Nagai H Brock M (eds): Intracranial Pressure V. Berlin: Springer-Verlag 1983 pp 301–306

34.

Saunders MLMiller JDStablein Det al: The effects of graded experimental trauma on cerebral blood flow and responsiveness to CO2. J Neurosurg 51:18261979Saunders ML Miller JD Stablein D et al: The effects of graded experimental trauma on cerebral blood flow and responsiveness to CO2. J Neurosurg 51:18–26 1979

35.

Siesjö BK: Brain Energy Metabolism. New York: John Wiley & Sons1978 pp 398451Siesjö BK: Brain Energy Metabolism. New York: John Wiley & Sons 1978 pp 398–451

36.

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

37.

Teasdale G: Assessment of head injuries. Br J Anaesth 48:7617661976Teasdale G: Assessment of head injuries. Br J Anaesth 48:761–766 1976

38.

Teasdale GJennett B: Assessment of coma and impaired consciousness. A practical scale. Lancet 2:81841974Teasdale G Jennett B: Assessment of coma and impaired consciousness. A practical scale. Lancet 2:81–84 1974

39.

Walker AEKollros JJCase TJ: The physiological basis of concussion. J Neurosurg 1:1031161944Walker AE Kollros JJ Case TJ: The physiological basis of concussion. J Neurosurg 1:103–116 1944

40.

Wei EPDietrich WDPovlishock JTet al: Functional, morphological, and metabolic abnormalities of the cerebral microcirculation after concussive brain injury in cats. Circ Res 46:37471980Wei EP Dietrich WD Povlishock JT et al: Functional morphological and metabolic abnormalities of the cerebral microcirculation after concussive brain injury in cats. Circ Res 46:37–47 1980

41.

Zsilla GRacagni GCheney DLet al: Constant rate infusion of deuterated phosphorylcholine to measure the effects of morphine on acetylcholine turnover rate in specific nuclei of rat brain. Neuropharmacology 16:25301977Zsilla G Racagni G Cheney DL et al: Constant rate infusion of deuterated phosphorylcholine to measure the effects of morphine on acetylcholine turnover rate in specific nuclei of rat brain. Neuropharmacology 16:25–30 1977

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