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  • Title: Time course of cerebral edema after traumatic brain injury in rats: effects of riluzole and mannitol.
    Author: Bareyre F, Wahl F, McIntosh TK, Stutzmann JM.
    Journal: J Neurotrauma; 1997 Nov; 14(11):839-49. PubMed ID: 9421455.
    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.
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