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

Abstract

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.

Keywords: glutamate transporter; levitiracetam; neuroinflammation; neuroplasticity; neuroprotection; traumatic brain injury.