Isoflurane preconditioning improves learning and memory functions in focal cerebral ischemia-reperfusion injury in rats by upregulating hippocampal AMPA receptor GluR1 subunit / 国际脑血管病杂志

ABSTRACT

Objective To investigate the effect of isoflurane preconditioning on rat learning and memory in cerebral ischemia-reperfusion injury and its possible mechanism.Methods Thirty-six adult male Sprague-Daw ley rats w ere randomly divided into a sham operation group, a cerebral ischemia-reperfusion group, and an isoflurane preconditioning group (n=12 in each group). A model of middle cerebral artery occlusion and ischemic-reperfusion w as induced by a modified intraluminal suture method. The rats of the isoflurane preconditioning group inhaled 1.5%isoflurane for 1 hour per day for 5 d. At 24 h after the last preconditioning, a model of MCAO w as made. At 24 h after MCAO, the infarct volume w as detected by using 2,3,5 chlorinated diphenyl tetrazolium staining. At day 1, 3, 7, and 14 after MCAO, the modified Neurological Severity Score (mNSS) were performed. At day 9 after MCAO, the Morris w ater maze test w as used to evaluate the learning and memory of rats. At day 14, Western blotting w as used to detect the protein expression level of hippocampal tissue glutamate receptor 1 (GluR1) on the side of ischemia. Results No obvious infarcts w ere observed in the rats of the sham operation group. The infarct volume in the isoflurane preconditioning group w as significantly smal er than that of the cerebral ischemia-reperfusion group (26.383%±3.128%vs.19.107%±1.661%;P<0.05). No neurological deficit w as observed in the sham operation group (score 0). The mNSS scores at day 1, 3, 7, and 14 after MCAO in the isoflurane preconditioning group w ere decreased significantly (day 19.000 ±1.195 vs.11.500 ±1.414;day 36.6250 ±1.407 vs.6.625 ±1.407vs.6.625 ±1.407; day 7 5.875 ±0.707 vs.7.375 ±1.407; and day 143.375 ±1.187 vs.5.125 ±1.246;al P<0.05). The Morris w ater maze show ed that the escape latencies at day 1-5 after MCAO in the isoflurane preconditioning group w ere al significantly shorter than those in the cerebral ischemia-reperfusion group (day 1 95.992 ±15.734 s vs.103.008 ±11.654 s; day 2 70.949 ±14.708 s vs. 94.705 ±14.709 s;day 339.660 ±7.413 s vs.65.716 ±10.155 s;day 422.692 ±5.778 s vs.35.240 ±8.553 s;day 5 14.906 ±4.336 s vs.22.890 ±10.381 s; al P<0.05). The numbers of crossing platform (4.556 ± 1.333 vs.2.889 ±1.536 ) and the percentages of time spent in the target quadrant ( 33.014%±5.223%vs. 21.978%±6.697%) in the isoflurane preconditioning group w ere significantly increased than in the cerebral ischemia-reperfusion group (al P<0.01). The levels of hippocampal GluR1 protein on the ischemic sides in the sham operation group, ischemia-reperfusion group, and isoflurane preconditioning group w ere 0.871 ±0.153, 0.456 ±0.130, and 0.689 ±0.126, respectively. There w ere significant differences among the 3 groups ( F=18.329, P<0.001) and the isoflurane preconditioning group w as significantly higher than the ischemia-reperfusion group (P<0.05). Conclusions Isoflurane preconditioning can improve the learning and memory in cerebral ischemia-reperfusion in rats, its mechanism may be associated w ith the uprelagating GluR1 expression in the hippocampus.