Protective effect of treatment with low-dose gliclazide in a model of middle cerebral artery occlusion and reperfusion in rats

• SUR1 involved in the ischemia/reperfusion injury in a rat MCAO model.
• Intravenously infusion of gliclazide could be neuroprotective.
• Gliclazide infusion at rate of 10 μg/h was more effective in decreasing apoptosis.
• Low doses of gliclazide caused only a slight reduction of serum glucose level.

The aim of this study was to explore the expression of sulfonylurea receptor 1 (SUR1), the regulatory subunit of the NCCa-ATP channel, and to investigate the protective effects of gliclazide following middle cerebral artery occlusion (MCAO)/reperfusion in male Wistar rats. Adult rats underwent 2 h of the left MCAO using the intraluminal thread technique before reperfusion. The core areas of the infarct at different reperfusion time points were examined for the mRNA level and protein expression of SUR1 using reverse transcription-polymerase chain reaction (RT-PCR) and western blotting respectively. Gliclazide was administered intravenously into the right jugular vein for 12 h simultaneously with the reperfusion. The number of apoptotic cells was determined using the TUNEL assay. The neurological functional deficits were evaluated using Bederson׳s test, and the cerebral infarction volume was visualized with TTC staining. We found up-regulation of SUR1 mRNA and protein levels in ischemic infarct tissues after reperfusion following MCAO, and SUR1 mRNA and protein were maximally upregulated 8–12 h after a 2-hour ischemia. The treatment with low-dose of gliclazide reduced the total number of TUNEL-positive cells, the neurological functional deficits and the brain infarct volume. These results suggest that the SUR1-regulated NCCa-ATP channel may be associated with MCAO/reperfusion injury and the infarct-reducing effects of intravenous treatment with gliclazide may be due, in part, to the blocked upregulation of SUR1 expression, the decreased infarct size and the reduced apoptosis in the ischemia–reperfusion brain.