Neuroprotection and anti-seizure effects of levetiracetam in a rat model of penetrating ballistic-like brain injury

• Published in: Restorative neurology and neuroscience Vol. 34; no. 2; pp. 257 - 270
• Main Authors: Caudle, Krista L., Lu, Xi-Chun M., Mountney, Andrea, Shear, Deborah A., Tortella, Frank C.
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 21.03.2016
• Subjects: Analysis of Variance; Animals; Disease Models, Animal; Electroencephalography; Gait Disorders, Neurologic - drug therapy; Gait Disorders, Neurologic - etiology; Gene Expression Regulation - drug effects; Head Injuries, Penetrating - complications; Head Injuries, Penetrating - drug therapy; Male; Maze Learning - drug effects; Motor Activity - drug effects; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Piracetam - analogs & derivatives; Piracetam - pharmacology; Piracetam - therapeutic use; Rats; Rats, Sprague-Dawley; Reaction Time - drug effects; Seizures - drug therapy; Seizures - etiology; Statistics, Nonparametric; Time Factors; Trauma Severity Indices; Treatment Outcome; cognitive function; motor; Traumatic brain injury; rat; post-traumatic seizures; neuroprotection
• DOI: 10.3233/RNN-150580
• ISSN: 0922-6028

Purpose: We assessed the therapeutic efficacy of FDA-approved anti-epileptic drug Levetiracetam (LEV) to reduce post-traumatic nonconvulsive seizure (NCS) activity and promote neurobehavioral recovery following 10% frontal penetrating ballistic-like brain injury (PBBI) in male Sprague-Dawley rats. Methods: Experiment 1 anti-seizure study: 50 mg/kg LEV (25 mg/kg maintenance doses) was given twice daily for 3 days (LEV3D) following PBBI; outcome measures included seizures incidence, frequency, duration, and onset. Experiment 2 neuroprotection studies: 50 mg/kg LEV was given twice daily for either 3 (LEV3D) or 10 days (LEV10D) post-injury; outcome measures include motor (rotarod) and cognitive (water maze) functions. Results: LEV3D treatment attenuated seizure activity with significant reductions in NCS incidence (54%), frequency, duration, and delayed latency to seizure onset compared to vehicle treatment. LEV3D treatment failed to improve cognitive or motor performance; however extending the dosing regimen through 10 days post-injury afforded significant neuroprotective benefit. Animals treated with the extended LEV10D dosing regimen showed a twofold improvement in rotarod task latency to fall as well as significantly improved spatial learning performance (24%) in the MWM task. Conclusions: These findings support the dual anti- seizure and neuroprotective role of LEV, but more importantly identify the importance of an extended dosing protocol which was specific to the therapeutic targets studied.