Michael K Tso1, Elliot Lass, Jinglu Ai, R Loch Macdonald. 1. 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.
Abstract
INTRODUCTION: 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. 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 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:SAHmice treated with VPA appeared to have improved neurobehavioral assessments at both 24 and 48 h compared to untreated SAHmice. VPA treatment in SAHmice also significantly decreased the number of degenerating neurons on fluoro-jade b staining. In VPA-treated SAHmice, there was a trend toward a decrease in the number of apoptotic neurons on caspase-3/NeuN immunohistochemistry. VPA did not significantly affect vasospasm. CONCLUSION: This study demonstrated that VPA improves neurological outcome and decreases brain injury in a mouse model of SAH.
Authors: Marcel A Kamp; Jasper H van Lieshout; Maxine Dibué-Adjei; Jasmin K Weber; Toni Schneider; Tanja Restin; Igor Fischer; Hans-Jakob Steiger Journal: Transl Stroke Res Date: 2017-01-30 Impact factor: 6.829