Effect Of Hyperglycemia And Insulin Intervention On The Cerebral Injury After Ischemia-reperfusion In Rats

ObjectivesTo explore the effect of hyperglycemia and insulin intervention on the cerebral injury after ischemia-reperfusion in rats and their potential mechanism, so to provide the new strategies for clinical treatment and prevention on ischemic stroke.MethodsThe 240 male SD rats were randomly divided into four groups: sham operation group, normal plasma glucose group, hyperglycemia and insulin intervention groups. All the rats except of those in the sham operation group were subjected with right middle cerebral artery occlusion for 2 hours and then reperfusion for 1, 6, 12 and 24 hours, respectively. The rats of hyperglycemia and insulin intervention groups were given streptozotocin (STZ) to induce hyperglycemia models. The neurologic functional scores, infarct sizes, numbers of apoptotic neurons around infarction region, proliferating neural stem cells (NSC) in hippocampus and the expression of IGF-I mRNA in infarction region of model rats were determined by means of the neurological severity score (NSS), triphenyl tetrazolium chloride (TTC) dye assay, TdT-mediated dUTP nick-END labeling (TUN-EL) assay, streptavidin-biotin-peroxidasecomplex (SABC) reaction, and reverse transcription - polymerase chain reaction (RT-PCR), respectively.ResultsCompared with those of normal plasma glucose group, the neurological function scores (t=4.06, 5.68, 5.42, 6.78, respectively, all P＜0.01), infarct sizes (t=11.60, 26.80, 23.94, 23.29, respectively, all P＜0.01) and the numbers of apoptotic neurons (t=6.83, 9.39, 4.23, 5.31, respectively, all P＜0.01) of the hyperglycemia group rats became worse significantly at the same reperfusion time. Moreover, those parameters in the insulin intervention group were better than those in the hyperglycemia group, even similar with those in the normal glucose group after 24h reperfusion.The expressions of IGF-ⅠmRNA in infarction region were stronger in hyperglycemia group rats after 6 and 12 hours reperfusion. Their expressions in the insulin intervention group rats, however, were persistently weaker at all the reperfusion time, particularly after 12 hours reperfusion.Compared with that in the sham operation rats, there were a bit of proliferation of NSCs in hippocampus of normal plasma glucose group rats after 24 hours reperfusion (t=4.68, P＜0.01). At the same perfusion time, there were no significant proliferation of NSCs in the rats of hyperglycemia and insulin intervention groups compared to that in the normal plasma glucose group (t=1.05, 0.28, both P＞0.05). During the 24 hours perfusion, there were no marked change of NSCs number both in hyperglycemia and insulin intervention groups (F=0.29, 0.50, respectively, both P＞0.05).ConclusionsAt 24 hours after ischemia-reperfusion, hyperglycemia could enlarge the infarct size, aggravate the damage of neurological function, increase the apoptotic neurons around infarction region, stimulate the expression of IGF-ⅠmRNA in infarction region, and inhabit the proliferating of neural stem cells in hippocampus of model rats. The effect of hyperglycemia on neurological function and infarct size perhaps by its effect of inducing neurons apoptosis around infarction region, however, had no relationship with the expression of IGF-ⅠmRNA in infarction region and proliferating of neural stem cells in hippocampus. While insulin maybe play the effect of neuroprotection by inhibiting the neuron apoptosis.