| BACKGROUND: In 1990, kitagawa et al found that the neuronal cells in the gerbil hippocampus developed a resistance to ischemic neuronal damage after a brief period of reversible ischemia. This phenomenon, which has been designated as "ischemic tolerance", has drawn attention in the hope that understanding the mechanism will lead to new therapy for neuronal ischemic damage. Unfortunately, the idea of exposure to brief periods of ischemia before an anticipated cerebral ischemic event does not appear to be clinically feasible. Recently, a number of substances such as TNF-a , IL-1, LPS have proven effective in inducing ischemic tolerance in the brain. However, the possibility of clinical application of these substances is yet to be elucidated because of their toxicity or side effects. Previous investigations have demonstrated that volatile anesthetics such as isoflurane are also similar to those observed during ischemic preconditioning in the heart, and protect the myocardium from ischemia-reperfusion damage. In our preliminary study we demonstrated that repeated isoflurance preconditioning reduced cerebral ischemic injury in transient middle cerebral artery occlusion(MCAO) rats. In this study, We examined the time--4-response and dose-response effects of isoflurane preconditioning to induce ischemic tolerance in MCAO rats model.OBJECTIVE1. To study the time-response relationship of isoflurane preconditioning on focal cerebral ischemic injury.2. To study the dose-response relationship of isoflurane preconditioning on focal cerebral ischemic injury.METHODS1. the time-response relationship of isoflurane preconditioning on focal cerebral ischemic injury.60 male Sprague-Dawley rats were randomly assigned to 6 groups (n = 10 in each group) based on pretreatments. Control group: rats received no pretreatment. O2 Group: rats received 100% oxygen every day for 5 days. Animals in isoflurane preconditioning groups received 1 hour of 1.5% isoflurane in 100% oxygen every day. But 1 day for Iso-1 group, 3 days for Iso-3 group, 5 days for Iso-5 group and 7 days for Iso-7 group. At 24h after the last treatment, transient MCAO was induced by introducing a 3-nylon monofilament suture through right internal carotid artery. Neurological deficit scores and infarct volume were used to assess the effect of isoflurane pretreatment.2. the dose-response relationship of isoflurane preconditionig on focal cerebral ischemic injury.Forty rats were randomly assigned to 4 groups(n = 10 in each group): Control group, 0.75% group, 1.50% group and 2.25% group. The animals in the last three groups received 0.75%, 1.50% and 2.25% isoflurane inhalation respectively Ih everyday for 5d. At 24h after the last treatment, transient MCAOwas induced by introducing a 3-nylon monofilament suture through right-5-internal carotid artery. Neurological deficit scores and infarct volume were used to assess the effect of isoflurane pretreatment.RESULTS1. the time-response relationship of isoflurane preconditioning on focal cerebral ischemic injury.The neurologic deficit scores of control group, O2 group, Iso-1 group, Iso-3 group, Iso-5 group and Iso-7 group were 2.25 ?0.71, 2+ 0.76, 1.88 ?0.84, 1 ?.93, 1+0.93, and 1?.07 respectively. The infarct volume were 198 ?42mm3, 188 ?8 mm3, 157?3 mm3, 94?2 mm3, 96?8 mm3 and 102 ?2 mm3 respectively. The neurologic deficit scores and the infarct volume of Iso-3 group, Iso-5 group and Iso-7 group were better than that of control group, O2 group and Iso-1 group (p<0.05), there were no significant differences among Iso-3 group, Iso-5 group and Iso-7 group (p>0.05).2. the dose-response relationship of isoflurane preconditioning on focal cerebral ischemic injury.The neurologic deficit scores of control group, 0.75% group, 1.50% group and 2.25% group were 2.7 ?.82, 2.0 + 0.67, 1.0 ?.67 and 0.7 ?.61 respectively. The infarct volume were 178.6?2.4mm3, 143.9?2.4 mm3, 94.9 ?7.3 mm3, 47.5?0 mm3 respectively. The neurologic deficit scores and the infarct volume... |
