6533b825fe1ef96bd12828c4

RESEARCH PRODUCT

MitoKATP-channel opener protects against neuronal death in rat venous ischemia.

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OBJECTIVE: Mitochondrial adenosine triphosphate-dependent potassium (mitoK ATP ) channels are present in the brain, and several reports have shown their neuroprotective, preconditioning effect against an ischemic insult. The role of mitoK ATP channels in the penumbra area has not been studied thoroughly. In a model of venous ischemia, widespread penumbra-like low flow areas are created, which are susceptible to cortical spreading depression. Thus, we studied effects of mitoK ATP channels on infarct size in this model. METHODS: Male Wistar rats were subjected to two-vein occlusion by photochemical thrombosis of two adjacent cortical veins combined with KCI-induced cortical spreading depression. The rats were assigned to four experimental groups pretreated intraventricularly 15 minutes before two-vein occlusion with 1) vehicle, 2) the mitoK ATP channel opener diazoxide (2 mmol/L), 3) diazoxide (2 mmol/L) plus the selective mitoK ATP channel blocker 5-hydroxydecanoate (5-HD; 100 mmol/L), or 4) 5-HD alone (100 mmol/L). Regional cerebral blood flow (laser Doppler scanning) and brain cell swelling (impedance) were monitored acutely. Infarct volume was assessed 7 days after ischemia. RESULTS: Pretreatment with diazoxide significantly reduced the infarct volume from 6.2 ± 0.7 mm' to 3.8 ± 0.4 mm 3 , whereas regional cerebral blood flow in the vicinity of the two veins was comparable in both groups 70 minutes after two-vein occlusion. Effects of diazoxide were abolished by 5-HD, whereas 5-HD alone even increased infarct volume. CONCLUSION: These results suggest that the opening of mitoK ATP channels plays a major role in brain protection under penumbra-like conditions, as shown in this venous occlusion model.