title: Valproic Acid treatment after experimental subarachnoid hemorrhage.
abstract: BACKGROUND
  Subarachnoid hemorrhage (SAH) can result in significant brain injury. Valproic acid (VPA), a widely-used anti-epileptic drug, was investigated as a possible neuroprotective drug in a prechiasmatic injection model of SAH in mice.
  
  
  METHODS
  Mice were randomized to the following experimental groups: SAH, SAH + VPA, Sham, and Sham + VPA. VPA (400 mg/kg) or saline was administered within 30 min of SAH induction and every 12 h thereafter for 48 h. Neurobehavioral assessments using the modified Garcia Score were conducted at 24 and 48 h. Brain injury was assessed at 48 h with fluoro-jade b and caspase-3/NeuN histo- and immunohistochemistry. Vasospasm was assessed in the MCA branches using hematoxylin & eosin histology.
  
  
  RESULTS
  SAH mice treated with VPA appeared to have improved neurobehavioral assessments at both 24 and 48 h compared to untreated SAH mice. VPA treatment in SAH mice also significantly decreased the number of degenerating neurons on fluoro-jade b staining. In VPA-treated SAH mice, there was a trend toward a decrease in the number of apoptotic neurons on caspase-3/NeuN immunohistochemistry. VPA did not significantly affect vasospasm.
  
  
  CONCLUSIONS
  This study demonstrated that VPA improves neurological outcome and decreases brain injury in a mouse model of SAH.
authors.affiliation: Division of Neurosurgery, Labatt Family Centre of Excellence in Brain Injury and Trauma Research, Keenan Research Centre of the Li KaShing Shing Knowledge Institute of St. Michael's Hospital, 30 Bond St., Toronto, ON, M5B 1W8, Canada.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Tso
authors.forename: Elliot
authors.initials: E
authors.lastname: Lass
authors.forename: Jinglu
authors.initials: J
authors.lastname: Ai
authors.forename: R
authors.initials: R
authors.lastname: Loch Macdonald
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D008297:Male; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011897:Random Allocation; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014635:Valproic Acid / Q000494:pharmacology*; D020301:Vasospasm, Intracranial / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology
chemical_list: D000927:Anticonvulsants; D018696:Neuroprotective Agents; D014635:Valproic Acid