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Swelling-induced activation of Volume Regulated Anion Channels (VRACs) during ischemia mediates excitatory amino-acid (EAA) release and takes part in ischemic-induced damage.In this project, we evaluate the expression of the volume regulated chloride channels in neonatal mice subjected to hypoxic-ischemic injury.In addition, we also evaluate the role of these channels in neonatal hypoxic-ischemic injury model using a selective VRAC blocker which is a specific antagonist of VRAC.The VACR blocker demonstrated a promising neuroprotective effect in adult brain ischemia only when given intracisternally.Unlike adult animals, in whom the blocker can not cross the blood-brain-barrier (BBB) when given intravenously, perinatal and neonatal animals have immature formations of BBB, and hence, the intraperitoneally application of the blocker shows sufficient to provide neuroprotection during hypoxic-ischemic conditions.In this study, cerebral hypoxic-ischemic injury was induced in postnatal seven-day-old mouse pups, and the mice which are treated with the blocker showed a significantly reduced mean percentage of right hemispheric corrected infarct volume compared to the vehicletreated mice.The treated mice also showed better functional recovery as they were more active than vehicletreated mice at 4 and 24-hour post injury.In addition, the VRAC blocker also reduced the OGD cell death in-vitro.These experiments further support the pathophysiological role of VRACs in ischemic brain injury, and suggest the blocker as a potential, easily administrable therapeutic drug targeting VRACs in the context of perinatal and neonatal hypoxic-ischemic brain injury.