title: Time course of cerebral edema after traumatic brain injury in rats: effects of riluzole and mannitol.
abstract: Brain trauma is the main cause of morbidity and mortality in young adults. One delayed events that occurs after a head trauma and compromises the survival of patients is cerebral edema. The present study examined first the occurrence of cerebral edema after a traumatic brain injury (TBI) induced by moderate fluid percussion in rats. Brain water content was measured from 1 h to 7 days posttrauma, in the hippocampus and cortex, on both ipsi- and contralateral hemispheres. Second, the effects of mannitol, an osmotic agent frequently used in the clinic, and riluzole, a neuroprotective compound, were investigated on regional edema formation. After TBI, the ipsilateral edema began early at 1-6 h, was maximal at 48 h and was resorbed by 5-7 days. No edema was observed in the contralateral hemisphere. Mannitol at 1 g/kg or vehicle was administered iv 15 min, 2 h and 4 h postinjury. At this dose, mannitol significantly attenuated the ipsilateral injured cortex edema measured at 6 h (p < 0.05). Riluzole at 4 and 8 mg/kg or vehicle was administered 15 min (IV) and 6 h, 24 h, and 30 h (SC) post-TBI. Riluzole at 4 x 4 mg/kg significantly reduced edema measured at 48 h, in the ipsilateral hippocampus (p < 0.05), whereas at 4 x 8 mg/kg, the reduction was observed in the hippocampus (p < 0.01) and the injured cortex (p < 0.05). Our results demonstrate that (1) cerebral edema begins early after the injury and is resorbed over 1 week; (2) mannitol could attenuate cerebral edema; and (iii) riluzole in addition to its neuroprotective effects reduces the brain edema. Thus, riluzole could be useful in human TBI treatment.
authors.affiliation: Rhône-Poulenc Rorrer S.A., Neurodegenerative Diseases Department, Vitry-Sur-Seine, France.
authors.forename: F
authors.initials: F
authors.lastname: Bareyre
authors.forename: F
authors.initials: F
authors.lastname: Wahl
authors.forename: T K
authors.initials: TK
authors.lastname: McIntosh
authors.forename: J M
authors.initials: JM
authors.lastname: Stutzmann
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000293:injuries / Q000503:physiopathology; D004234:Diuretics, Osmotic / Q000494:pharmacology*; D007839:Functional Laterality; D006624:Hippocampus / Q000293:injuries / Q000503:physiopathology; D007700:Kinetics; D008297:Male; D008353:Mannitol / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010474:Percussion; D051381:Rats; D017207:Rats, Sprague-Dawley; D019782:Riluzole / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D004234:Diuretics, Osmotic; D018696:Neuroprotective Agents; D008353:Mannitol; D019782:Riluzole