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Experimental Researches Of The Neuroprotective Effect Of Insulin On Brain Ischemia

Posted on:2002-10-30Degree:DoctorType:Dissertation
Country:ChinaCandidate:B LiFull Text:PDF
GTID:1104360032452458Subject:Surgery
Abstract/Summary:PDF Full Text Request
Insulin, as one of regulating the blood glucose incretion, has a beneficial effect on brain ischemic damage by its down regulate the blood glucose values effect. In the early stage, many papers had reported that regulating the glucose values in the low-normal range with administration of insulin post brain ischemia could attenuate ischemic brain damage. Along with the insulin and its receptor being detected in central nervous system (CNS), the effect of insulin on CNS has caught people's attention. In recent year, some researches indicate that the protective effect of insulin on brain ischemia does not only depend on its hypoglycemic effect, but also relies on the neuroprotective effect. Unfortunately, as the mechanism of the neuroprotective effect of insulin on brain ischemia is not clear, it limites the application of insulin in clinic treatment for brain ischemic insult. In the present study with SD rats as objects, we established a standard animal global brain ischemia model and explored the mechanism of the neuroprotective effect of insulin on brainischemia.I .Establishing the rat standard global brain ischemic model by modified four-vessel occlusion (4-VO) method. To modify the traditional 4-VO method, first, the double alar foramina of the first cervical vertebra were enlarged by microdrill to expose the vertebral artery, and then cauterized the vertebral artery under the direct visualization with microscope. Second, the changes of electrocorticogram (ECG) were dynamic monitored pre and post brain ischemia, and the silent ECG appeared post ischemia as was a criterion to judge weather the complete global brain ischemia was achieved. The morphological criterion, by which the neurons in rat hippocampal CA1 region almost died 7 days following brain ischemia, was applied to judge weather the model was well established. In this study, there were 26 rats that achieved the standard of complete global brain ischemia judged by the silent ECG criterion, and the neurons in hippocampal CA1 region of these rats were almost dead. Even though, 24 rats achieved the complete global brain ischemia judged by the traditional criterion based on the sign of the whitening of the eye ball and the disappearing of the upturning reflection post brain isachmia, in only 21 rats, the neurons in the hippocampal CA1 region were almost dead. The reliability of the traditional criterion was 87.5%(21/24). Judged by the morphological criterion, the ratio of successfully established global brain ischemic model by the modified 4-VO method was 86.7% (26/30) . That was higher than that by the traditional 4-VO method which was only 70%(21/30). The result indicated that using this modified 4-VO method to establish the rat global brain ischemic model can improve the reliability and successful ratio.II .The global brain ischemiac model of rat was established with the methodthat has been described above. One unit of insulin was injected into the rat brain ventricular immediately post re-perfusion. After that, the changes of the blood glucose and the pathological changes of the neurons of the hippocampal CA1 region at 1, 3, 5, 7d and the 8 weeks post brain ischemia were observed, and the ability of the memory at the 8 weeks post brain ischemia was tested. The blood glucose values between the rats of the treated group and the rats of the ischemic group were not significantly different post brain ischemia. At l,3,5,7d and 8 weeks post brain ischemia, the count of the normal neurons of CA1 region in the treated group was 168.6?10.9,133.5 + 10.5,105.6?10.1 and 102.7?10.2, respectively,that was higher than that in the ischemic group 87.4?.4,45.4?.1,10.5?.4 and 10.3?.6 Respectively. Eight weeks later, the ability of memory of the rats was tested by the bisection "Y" maze. The requiring times of electric shock to attain the criterion of 9 correct response out of 10 tests were 9.6 ?1.4 in the treated group, that was lower than that in the ischemic group which were 18.6 + 2.6. The result demonstrated that insulin has exactly...
Keywords/Search Tags:insulin, brain ischemia, neuroprotective effect, apoptosis of neuron, Bcl-2 family gene
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