2005 Volume 16 Issue 2 Pages 87-93
Ischemic preconditioning in brain is well documented and several reports have shown that this phenomenon is mediated by activation of mitochondrial ATP-dependent potassium (mitoKATP) channels. However, the role of mitoKATP channels in the penumbra area has not been studied thoroughly. In a model of venous ischemia, large penumbra-like low flow areas and few no flow areas are created which are susceptible to spreading depression (CSD). Thus, we studied effects of mitoKATP channels on infarct development in this model. Male Wistar rats were subjected to 2-vein occlusion (2VO) by photochemical thrombosis of two adjacent cortical veins, combined with 10 KCl-induced CSD and assigned to three experimental groups pretreated intraventricularly before 2VO with vehicle, diazoxide; a mitoKATP channel opener, and diazoxide + 5-hydroxydecanoate (5-HD); a selective mitoKATP channel blocker. Regional cerebral blood flow (rCBF) and impedance were monitored, and infarct volume was assessed 7 days after ischemia. Pretreatment with diazoxide significantly reduced the infarct volume, while rCBF in the vicinity of the two veins at 70 min after 2VO was comparable in both groups. On the other hand, the mean amplitude of impedance changes evoked by CSD was decreased by pretreatment with diazoxide. These effects of diazoxide were abolished by 5-HD. These results suggest that activation of mitoKATP channels plays a major role in neuronal death under penumbra-like conditions as shown in venous ischemia.
