Neuroscience Vol. 28, No. I, pp. 233-244,1989 Printed in Great Britain 0306-4522/89 $3.00 + 0.00 Pergamon Press plc IBRO TRAUMATIC BRAIN INJURY IN THE RAT: CHARACTERIZATION OF A LATERAL FLUID-PERCUSSION MODEL T. K. MCINWXH,*~ R. VINK,$ L. NOBLE,~ I. YAMAKAMI,~S. FERNYAK,~ H. SOAR@ and A. L. FADENS $%&al Research Center, Department of Surgery, University of Connecticut Health Center, Farmington, CT 06032, U.S.A. JDepartment of Neurology, University of California, San Francisco; and Center for Neural Injury, San Francisco Veterans Administration Medical Center, San Francisco, CA 94121, U.S.A. Abstract-Experimental fluid-percussion models produce brain injury by rapidly injecting saline into the closed cranium. In the present study we characterize the physiological, histopathological and neurological responses to mechanical brain injury in the rat produced by lateral fluid-percussion injury of graded severity. Physiological experiments (n = 105) demonstrated that all levels of injury produced an acute and transient systemic hypertension and bradycardia. Acute hypertension followed by significant hypotension occurred at higher magnitudes of injury. Post-injury suppression of electroencephalographic amplitude was related to the severity of injury. An increase in slow wave (delta/theta) electroencephalographic activity with a concomitant decrease in alpha/beta electrocncephalographic activity were observed only at moderate and high magnitude of injury and were correlated with a worsened neurological outcome (r = 0.84; P < 0.05) and increased mortality (r = 0.66; P < 0.05). Alterations in brainstem auditory- evoked potentials were also observed only at the higher levels of injury. Histopathological analysis revealed that the extent of post-injury hemorrhage, cavitation and vascular disruption (as measured by extravasation of Evans Blue dye) was greater at the higher magnitudes of injury. Neurological scoring performed over a 4-week post-injury period demonstrated that lateral fluid-percussion brain injury produces a chronic neurological deficit that is directly related to the severity of injury. Survival was also significantly reduced at the higher magnitudes of injury. These data demonstrate that the lateral model of fluid-percussion injury in the rat reproduces many of the features of head injury observed in other models and species and may therefore be a useful experimental model for the study of the pathophysiology of traumatic brain injury. Experimental models of traumatic brain injury attempt to recreate reproducible and clinically relevant pathological conditions through the applica- tion of mechanical forces. These models include devices that accelerate or rotate the skull,” induce impact to intact and freely moving cranium,z’ in- duce impact to a fixed, immobilized cranium,12 and rapidly inject physiological saline into a closed cranium (fluid-percussion).29 Fluid-percussion injury appears to reproduce some aspects of the bio- mechanical, physiological, neurological and morpho- pathological responses observed in human closed head injury. 29 The technique produces pressure transients (-20 ms) similar to those recorded in human cadaver skulls during sudden impact,‘* neuro- logical signs of behavioral suppression resembling unconsciousness in humans,” reduction or abo- lition of cerebrovascular responsiveness to changes to PC&, 33 loss of pressure autoregulation,l’ im- *To whom correspondence should be addressed. Abbreviations: ABGs, arterial blood gases; BAERs, brain- stem auditory evoked potentials; CSE, compressed spectral edge; EBA, Evans Blue Albumin; EEG, elec- troencephalographic; FFT, fast Fourier-transformed; ICP, intracranial pressure; MAP, mean arterial pressure. mediate26 and late developingz4 increases in intracra- nial pressure, and edema, probably of vasogenic origin.’ Most fluid-percussion studies have been performed in the cat,‘3S’4*29 and rabbit.19 However, the develop- ment of a rat model of fluid-percussion brain injury would be advantageous with regard to the ease of animal care, the ability to study a large number of animals, the high resistance to infection of this species and the likelihood that other investigators would be able to implement a similar model in their laborato- ries. Hayes and colleagues have recently begun to examine the physiological and behavioral response to midline (vertex) fluid-percussion in the rat,* whereas F’itts and co-workers have successfully utilized a combined hypoxia/trauma rat model of fluid-percus- sion injury.15 In the present study, we endeavor to characterize the physiological, histopathological and neurological responses to mechanical brain injury in the rat produced by lateral (parasagittal) fluid-percus- sion injury of graded severity. We chose to evaluate a lateral model of fluid-percussion brain injury, since it may cause greater cortical damage or shearing with less direct brainstem compression, and may, there- fore, be more clinically relevant than the conventional vertex model. 233