title: The neuroprotective effect of diazoxide is mediated by mitochondrial ATP-dependent potassium channels in a rat model of acute subdural hematoma.
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 (mitoK(ATP)) channels have a major role in cerebral ischemic preconditioning in vivo and in vitro. However, the role of the mitoK(ATP) channel has not been investigated in the context of ASDH. Thus, the purpose of this study was to determine whether the mitoK(ATP) channel mediates neuroprotection in a rat model of ASDH. Male Wistar rats were subjected to subdural infusion of 400 μL autologous venous blood. The rats were assigned to four experimental groups pretreated intraventricularly 15 minutes before ASDH with (1) vehicle (n=10); (2) the mitoK(ATP) channel agonist diazoxide (n=9); (3) diazoxide plus the selective mitoK(ATP) channel antagonist 5-hydroxydecanoate (5-HD) (n=6); or (4) 5-HD alone (n=6). Infarct volume was assessed at 4 days 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 mitoK(ATP) channel is an important mediator of the neuroprotective effects of cerebral preconditioning in a rat model of ASDH.
authors.affiliation: Department of Neurosurgery, Nara Medical University, Shijo-cho 840, Kashihara 634-8521, Japan. nakagawa@naramed-u.ac.jp
authors.forename: Ichiro
authors.initials: I
authors.lastname: Nakagawa
authors.forename: Daisuke
authors.initials: D
authors.lastname: Wajima
authors.forename: Kentaro
authors.initials: K
authors.lastname: Tamura
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Nishimura
authors.forename: Young-Su
authors.initials: YS
authors.lastname: Park
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakase
mesh_terms: D000818:Animals; D020520:Brain Infarction / Q000209:etiology* / Q000517:prevention & control*; D003652:Decanoic Acids / Q000627:therapeutic use; D003981:Diazoxide / Q000627:therapeutic use*; D004195:Disease Models, Animal; D020199:Hematoma, Subdural, Acute / Q000150:complications* / Q000188:drug therapy; D006880:Hydroxy Acids / Q000627:therapeutic use; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003652:Decanoic Acids; D006880:Hydroxy Acids; D018696:Neuroprotective Agents; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; C052853:5-hydroxydecanoic acid; D003981:Diazoxide