title: Riluzole attenuates cortical lesion size, but not hippocampal neuronal loss, following traumatic brain injury in the rat.
abstract: The neuroprotective effects of Riluzole, a compound with several mechanisms of action including the inhibition of sodium channel activity and glutamate release, were evaluated in a rat model of parasagittal fluid-percussion (FP) brain injury. Male Sprague-Dawley rats (350-400 g, n = 17) were anesthetized with sodium pentobarbital (60 mg/kg i.p.) and 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), followed by subcutaneous injections (identical dose) at 6 hr and 24 hr. Two 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 computerized image analysis system. Administration of Riluzole significantly 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 unaffected by Riluzole treatment. The present study demonstrates that Riluzole can attenuate cortical lesion size following brain trauma. These neuroprotective effects may be related to the synergy of the different mechanisms of action of Riluzole.
authors.affiliation: Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia 19104-6316, USA.
authors.forename: C
authors.initials: C
authors.lastname: Zhang
authors.forename: R
authors.initials: R
authors.lastname: Raghupathi
authors.forename: K E
authors.initials: KE
authors.lastname: Saatman
authors.forename: D H
authors.initials: DH
authors.lastname: Smith
authors.forename: J M
authors.initials: JM
authors.lastname: Stutzmann
authors.forename: F
authors.initials: F
authors.lastname: Wahl
authors.forename: T K
authors.initials: TK
authors.lastname: McIntosh
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000473:pathology*; D002470:Cell Survival / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects* / Q000473:pathology; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019782:Riluzole / Q000494:pharmacology*
chemical_list: D018696:Neuroprotective Agents; D019782:Riluzole