Lubeluzole following traumatic brain injury in the rat

Lubeluzole, a novel nitric oxide synthase (NOS) pathway modulator, was show n to be neuroprotective in cerebral ischemia as studied in animal models an d clinical trials. The present study investigated the effect of lubeluzole on contusion volume and brain edema following traumatic brain injury. Sprag ue-Dawley rats (n = 36) were subjected to cortical impact injury. Lubeluzol e (0.8 mg/kg i.v.; n = 18) or a corresponding volume of vehicle (n = 18) wa s injected 15 and 75 minutes following trauma. Animals were sacrificed 24 h ours following trauma. Contusion volume was measured planimetrically from c oronal slices stained with hematoxylin and eosin. In this group, T-2-weight ed magnetic resonance imaging (MRI) was also performed 90 minutes and 6 and 24 hours after trauma. Hemispheric swelling and water content were determi ned gravimetrically 24 hours after trauma. In this group, intracranial pres sure (ICP), mean arterial blood pressure (MABP), and cerebral perfusion pre ssure (CPP) were monitored for 30 minutes before sacrifice. Lubeluzole did not reduce contusion volume, hemispheric swelling, or water content. ICP, M ABP, and the resulting CPP did not differ between treated and untreated rat s 24 hours after injury. T-2-weighted MRI revealed a higher volume of edema at 90 minutes after trauma in treated rats. However, at 6 and 24 hours aft er trauma, no significant difference was discernible. Under these experimen tal conditions, lubeluzole fails to exert beneficial effects following expe rimental traumatic brain injury (TBI).