title: Valproate prevents epileptiform activity after trauma in an in vitro model in neocortical slices.
abstract: OBJECTIVE
  Epileptogenesis is a hallmark of severe cortical trauma, with up to approximately 80% of patients experiencing seizures in the first 24 hours after penetrating head injury. An in vitro model of traumatic brain injury was developed to investigate hyperexcitability and epileptogenesis and their prevention. We determined whether sodium valproate would prevent epileptiform activity in this experimental model.
  
  
  METHODS
  Rat cortical slices were prepared and maintained in vitro using standard methods. Trauma was effected by removing the superficial 450-500 microm of slices. Traumatized slices were exposed to valproate at various time points. Intracellular and extracellular recordings were used to assess evoked activities.
  
  
  RESULTS
  In untreated traumatized deep segments, hyperexcitability was manifested by depressed inhibition and often (54%) by epileptiform activity. Preparations exposed to valproate at 30 minutes or later after trauma showed abnormal activity similar to control traumatized slices. Epileptogenicity in deep segments was significantly reduced when slices were exposed to valproate (a) continuously immediately after trauma, (b) after a 20-minute delay, or (c) immediately after trauma for 1 hour and then returned to physiological solution. Finally, slices that were exposed to valproate or pentobarbital beginning 20 minutes after trauma for only 1 hour and then returned to physiological medium showed a significant reduction in abnormal activity. Valproate was found to enhance fast gamma-aminobutyric acid(A)-ergic inhibitory strength.
  
  
  CONCLUSIONS
  Valproate significantly reduces epileptiform activity after trauma to the neocortex, likely by restoring the excitation-inhibition balance, perhaps through augmentation of gamma-aminobutyric acid transmission. The timing of this action may have implications for mechanisms of seizure genesis and may suggest a role for rapid treatment.
authors: Department of Physiology and Pharmacology, State University of New York Downstate Medical Center, Brooklyn, New York 11203, USA.
authors: L
authors: L
authors: Yang
authors: L S
authors: LS
authors: Benardo
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001930:Brain Injuries / Q000150:complications*; D004195:Disease Models, Animal; D004827:Epilepsy / Q000517:prevention & control*; D006801:Humans; D066298:In Vitro Techniques; D019579:Neocortex / Q000293:injuries* / Q000503:physiopathology; D009433:Neural Inhibition / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013003:Somatosensory Cortex / Q000293:injuries / Q000503:physiopathology; D009435:Synaptic Transmission / Q000502:physiology; D014635:Valproic Acid / Q000627:therapeutic use*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D000927:Anticonvulsants; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid