TIME-COURSE OF CEREBRAL EDEMA AFTER TRAUMATIC BRAIN INJURY IN RATS - EFFECTS OF RILUZOLE AND MANNITOL

Brain trauma is the main cause of morbidity and mortality in young adu lts. One delayed events that occurs after a head trauma and compromise s the survival of patients is cerebral edema. The present study examin ed first the occurrence of cerebral edema after a traumatic brain inju ry (TBI) induced by moderate fluid percussion in rats. Brain water con tent was measured from 1 h to 7 days posttrauma, in the hippocampus an d cortex, on both ipsi-and contralateral hemispheres. Second, the effe cts of mannitol, an osmotic agent frequently used in the clinic, and r iluzole, a neuroprotective compound, were investigated on regional ede ma formation. After TBI, the ipsilateral edema began early at 1-6 h, w as 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 ad ministered iv 15 min, 2 h and 4 h postinjury. At this dose, mannitol s ignificantly attenuated the ipsilateral injured cortex edema measured at 6 h (p < 0.05). Riluzole at 4 and 8 mg/kg or vehicle was administer ed 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 ipsilater al hippocampus (p < 0.05), whereas at 4 x 8 mg/kg, the reduction was o bserved 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 c erebral edema; and (iii) riluzole in addition to its neuroprotective e ffects reduces the brain edema. Thus, riluzole could be useful in huma n TBI treatment.