Neuroprotective, neuroplastic, and neurobehavioral effects of daily treatment with levetiracetam in experimental traumatic brain injury.

Background: Prophylactic treatment with antiepileptic drugs (AEDs) has been recommended to prevent early seizure onset in patients with traumatic brain injury (TBI). However, the potential neuroprotective and/or detrimental effects of prophylactic AED treatment on behavioral and cognitive function after TBI are not well studied.

Objective: To investigate the effects of a novel AED, levitiracetam (LEV), on behavioral and cognitive function after experimental TBI in rats.

Methods: Adult male rats were administered LEV (intraperitoneal 50 mg/kg) or vehicle (saline; SL) daily for 20 days beginning 1 day after controlled cortical impact (CCI; 2.8 mm; 4 m/s) or sham surgery. Beam performance (days 1-6), Y-maze (day 7), and Morris water maze (days 14-19) postinjury testing was assessed.

Results: Daily LEV treatment improved motor function, increased novel arm exploration in the Y-maze, elicited greater hippocampal cell sparing, and decreased contusion volumes compared with CCI/SL rats. Daily LEV administration also reversed a TBI-induced decrease in regional glutamate transporter expression and neuroplastic marker proteins present 20 days post-CCI. Also, daily LEV treatment decreased regional IL-1β expression after TBI.

Conclusions: These results suggest that daily LEV treatment has beneficial effects on histological, molecular, and behavioral elements of neurological recovery after TBI, in part, via modulation of neuroinflammatory and excitatory pathways.