title: Neuroprotection and anti-seizure effects of levetiracetam in a rat model of penetrating ballistic-like brain injury.
abstract: OBJECTIVE
  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.
authors.forename: Krista L
authors.initials: KL
authors.lastname: Caudle
authors.forename: Xi-Chun M
authors.initials: XC
authors.lastname: Lu
authors.forename: Andrea
authors.initials: A
authors.lastname: Mountney
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Shear
authors.forename: Frank C
authors.initials: FC
authors.lastname: Tortella
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D004569:Electroencephalography; D020233:Gait Disorders, Neurologic / Q000188:drug therapy / Q000209:etiology; D005786:Gene Expression Regulation / Q000187:drug effects; D020197:Head Injuries, Penetrating / Q000150:complications* / Q000188:drug therapy*; D000077287:Levetiracetam; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D010889:Piracetam / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D012640:Seizures / Q000188:drug therapy* / Q000209:etiology*; D018709:Statistics, Nonparametric; D013997:Time Factors; D015599:Trauma Severity Indices; D016896:Treatment Outcome
chemical_list: D018696:Neuroprotective Agents; D000077287:Levetiracetam; D010889:Piracetam
keywords: Traumatic brain injury; cognitive function; motor; neuroprotection; post-traumatic seizures; rat