Effect of isoflurane preconditioning on expression of hippocampal GluR1 subunits-containing AMPA receptors in a rat model of focal cerebral ischemia-reperfusion

Abstract

Objective To evaluate the effect of isoflurane preconditioning on the expression of hippocampal GluR1 subunits-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate(AMPA)receptors in a rat model of focal cerebral ischemia-reperfusion(I/R). Methods Forty-eight pathogen-free healthy male Sprague-Dawley rats, weighing 250-280 g, aged 7-8 weeks, were divided into 3 groups(n=16 each)using a random number table: sham operation group(group S), focal cerebral I/R group(group I/R)and isoflurane preconditioning group(group IPC). Focal cerebral I/R was induced by occlusion of the middle cerebral artery for 2 h followed by reperfusion to induce cognitive decline in I/R and IPC groups. Rats were exposed to 1.5% isoflurane for 1 h every day for 5 consecutive days, and the model was established at 24 h after the last exposure in group IPC. Eight rats in each group were selected to perform Morris water maze test for 6 consecutive days starting from 9 or 23 days after operation. The rats were sacrificed at 14 and 28 days after operation, and the hippocampal tissues were obtained for determination of the expression of GluR1 mRNA(by using real-time polymerase chain reaction)and GluR1 protein(by Western blot). Results Compared with group S, the escape latency was significantly prolonged at each time point after operation, the frequency of crossing the original platform quadrant and percentage of swimming distance at the original platform quadrant were decreased at 14 and 28 days after operation, and the expression of GluR1 protein and mRNA was down-regulated at 14 days after operation in I/R and IPC groups(P<0.05). Compared with group I/R, the escape latency was significantly shortened at 10-13 days after operation, the percentage of swimming distance at the original platform quadrant and frequency of crossing the original platform quadrant were increased at 14 days after the operation, and the expression of GluR1 protein and mRNA was up-regulated at 14 days after operation in group IPC(P<0.05). Conclusion The mechanism by which isoflurane preconditioninig improves the cognitive function is related to up-regulation of the expression of hippocampal GluR1 subunits-containing AMPA receptors in a rat model of focal cerebral I/R. Key words: Isoflurane; Ischemic preconditioning; Brain; Reperfusion injury; Hippocampus; Receptors, AMPA