The Effect Of Isoflurane Preconditioning On Cognitive Function And Hippocampal AMPA Receptor GluR1 Subunit Expression In Rats With Vascular Dementia

Objective: To evaluate the effect of isoflurane preconditioning on cognitive function and hippocampal AMPA receptor GluR1 subunit expression in rats with vascular dementia. Methods: Sixty healthy male Sprague-Dawley rats, aged 7-8weeks,weighing 250-180 g,were randomly divided into 3 groups(n = 20 each) using a random number table: sham operation group(Sham group), vascular dementia group(VD group) and isoflurane preconditioning group(IPC group). Rats in the Sham group were subjected to the separation of right internal carotid arterty. The model of vascular dementia was produced by occlusion of the middle cerebral artery for 2h followed by reperfusion in VD and IPC groups. Rats in group IPC were exposed to1.5% isoflurane for 1 hour per day in total of 5 days. Middle cerebral artery occlusion was performed at 24 h after the end of preconditioning. 24 hours after operation, 2-3-5-triphenyl tetrazolium chloride staining was used to detect cerebral infarct volume.On 1, 3, 7, 14, 28 d after operation, neurological denficiency was evaluated by the modified neurological severity score. Morris maze water test was performed starting on day 9 and day 23 after operation respectively, the escape latency, frequency of crossing the original platform and swimming time percentage of the original platform quadrane were recorded. The rats in each groups were sacrificed on 14 and 28 days after operation and the hippocampal tissues were obtained for determination of the expression of mRNA(by using RT-PCR) and protein(by using Western blot) of GluR1. Results: TTC staining showed that no infarct was observed in the Sham group,the obvious cerebral infarct was observed in VD and IPC group. The infarct size in the IPC group was significantly lower than that in the VD group(P<0.05). The modified neurological deficit score showed that no neurological deficit was observed in the sham operation group(score 0), the variable degrees of neurological deficitwere observed VD and IPC group at different time points after operation. The neurological deficit score at 1, 3, 7, 14 days after operation in the IPC group was significantly lower than that in the VD group(P<0.05). The Morris water maze showed, compared with Sham group, the escape latency was prolonged, swimming time percentage of the original platform quadrant and frequency of crossing the origsinal platform were decreased in VD and IPC groups(P<0.05). Compared with VD group, The escape latency was shorten at 10~13 days after operation in IPC group,and swimming distance percentage of the original platform and frequency of crossing the original platform were increased at 14 days after the operation in IPC group(P<0.05). Compared with Sham group, the expression GluR1 mRNA and protein were down-regulated at 14 days after operation in VD and IPC groups(P<0.05). Compared with VD group, the expression GluR1 mRNA and protein were up-regulated at 14 days after operation in IPC group(P<0.05). Conclusion: The cerebral ischemia reperfusion injury can injury the rats hippocampus neurons and lead to cognitive dysfunction. Isoflurane preconditioninig reduces cerebral ischemia reperfusion injury and improves cognitive function by up-regulating the expression of the mRNA and protein of GluR1 of hippocampus in rats with vascular dementia.