Lubeluzole treatment does not attenuate neurobehavioral dysfunction or CA3hippocampal neuronal loss following traumatic brain injury in rats

Purpose: One of the downstream consequences of glutamate-induced NMDA (N-me thyl-D-aspartate) receptor activation following traumatic brain injury (TBI ) is production of nitric oxide (NO). Ln this study, we evaluated the abili ty of lubeluzole, a novel neuroprotective compound which downregulates the glutamate-activated nitric oxide pathway and blocks sodium and voltage-sens itive calcium channels, to improve behavioral and histological outcome in r ats following TBI. Methods: Rats were anesthetized and subjected to moderate lateral fluid per cussion brain injury (2.4-2.6 atm) or were surgically prepared but not inju red (sham). Fifteen minutes after injury, animals received a bolus of eithe r vehicle (n = 12 injured, n = 14 uninjured) or lubeluzole (0.31 mg/kg, n = 12 injured, n = 8 uninjured) through the jugular vein followed by a one ho ur infusion of vehicle or lubeluzole (0.31 mg/kg). Animals were tested at 4 8 hours post-injury for cognitive performance in the Morris water maze, neu romotor function, and limb placing function, and then sacrificed. Results: While brain injury resulted in significant cognitive and motor def icits, injured animals treated with lubeluzole did not differ in spatial me mory performance, neuromotor score, or limb placing function from injured, vehicle-treated animals. Furthermore, there was no difference in the mean n umber of ipsilateral hippocampal CA3 neurons between injured rats treated w ith vehicle and those treated with lubeluzole. Conclusions: This single-dose study failed to demonstrate a beneficial effe ct of lubeluzole on the acute behavioral or histological sequelae following TBI.