Abstract
Acute subdural hematoma (ASDH) results in neuronal death due to mitochondrial dysfunction and a subsequent cascade of apoptotic and necrotic events. We previously demonstrated that mitochondrial ATP-dependent potassium (mitoKATP) channels have a major role in cerebral ischemic preconditioning in vivo and in vitro. However, the role of the mitoKATP channel has not been investigated in the context of ASDH. Thus, the purpose of this study was to determine whether the mitoKATP channel mediates neuroprotection in a rat model of ASDH. Male Wistar rats were subjected to subdural infusion of 400μL autologous venous blood. The rats were assigned to four experimental groups pretreated intraventricularly 15 minutes before ASDH with (1) vehicle (n=10); (2) the mitoKATP channel agonist diazoxide (n=9); (3) diazoxide plus the selective mitoKATP channel antagonist 5-hydroxydecanoate (5-HD) (n=6); or (4) 5-HD alone (n=6). Infarct volume was assessed at 4days after ASDH. Brain edema formation was also measured. Pretreatment with diazoxide significantly reduced infarct volume and brain edema formation after ASDH. However, the effects of diazoxide were abolished by co-treatment with 5-HD. 5-HD alone increased infarct volume. These data suggest that the mitoKATP channel is an important mediator of the neuroprotective effects of cerebral preconditioning in a rat model of ASDH.
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