RILUZOLE ATTENUATES CORTICAL LESION SIZE, BUT NOT HIPPOCAMPAL NEURONAL LOSS, FOLLOWING TRAUMATIC BRAIN INJURY IN THE RAT

The neuroprotective effects of Riluzole, a compound with several mecha nisms of action including the inhibition of sodium channel activity an d glutamate release, were evaluated in a rat model of parasagittal flu id-percussion (FP) brain injury. Male Sprague-Dawley rats (350-400 g, n = 17) were anesthetized with sodium pentobarbital (60 mg/kg i.p.) an d subjected to parasagittal FP brain injury of moderate severity (2.3- 2.5 atm), Fifteen min following injury, animals randomly received an i ,v, bolus of either Riluzole (8 mg/kg, n = 8) or vehicle (n = 9), foll owed by subcutaneous injections (identical dose) at 6 hr and 24 hr, Tw o weeks after injury and drug treatment, animals were sacrificed and a series of brain sections, stained with Hematoxylin and Eosin (H&E) or cresyl violet, were evaluated for quantitative cortical lesion volume and cell counts of hippocampal CA3 neurons, respectively, using a com puterized image analysis system. Administration of Riluzole significan tly reduced FP-induced tissue loss in the temporal/occipital cortices ipsilateral to the site of impact by 46%, compared to vehicle-treated, brain-injured animals (P = 0.01), In contrast, the selective neuronal loss observed in the CA3 region of the ipsilateral hippocampus was un affected by Riluzole treatment. The present study demonstrates that Ri luzole can attenuate cortical lesion size following brain trauma. Thes e neuroprotective effects may be related to the synergy of the differe nt mechanisms of action of Riluzole. (C) 1998 Wiley-Liss, Inc.