Valproic acid treatment after experimental subarachnoid hemorrhage

Abstract

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 modifi ed Garcia Score were conducted at 24 and 48 h. Brain injury was assessed at 48 h with fl uoro-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 signifi cantly decreased the number of degenerating neurons on fl uoro-jade b staining. In VPAtreated SAH mice, there was a trend toward a decrease in the number of apoptotic neurons on caspase-3/NeuN immunohistochemistry. VPA did not signifi cantly affect vasospasm. Conclusion : This study demonstrated that VPA improves neurological outcome and decreases brain injury in a mouse model of SAH. Introduction : Subarachnoid hemorrhage (SAH) can result in signifi cant 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.