Mechanisms and Effects of Ischemic Postconditioning on Hippocampus rCBF and VEGF Following Cerebral Ischemic in Tree Shrews
|School||Kunming Medical College|
|Keywords||Photochemical Adapt thrombosis after ischemia Vascular endothelial growth factor Regional cerebral blood flow Cerebral artery occlusion Hippocampus Tree ( shrews )|
BACKGROUND: Cerebral ischemia, a major cause of mortality in our country, is characterized by insufficient blood supply to regions of the brain which leads to tissue necrosis (infarction). Therefore to be a hot spot and investigative emphasis for basic and clinical medicine.Thus the mechanism of neuroprotection of cerebral ischemia has been an important area in cerebrovascular disease.But ischemic postconditioning is a novel strategy to harness nature’s protection against myocardial ischaemia-reperfusion injury. Basis of it ,we study the effect of ischemic postconditioning on hippocampus regional cerebral blood flow (rCBF) and vascular endothelial growth factor(VEGF) following diffent cerebral ischemic model(including focal thrombotic cerebral ischemia and middle cerebral artery occlusion) in tree shrews.OBJECTIVE: To approach the interrelationship between rCBF and VEGF on hippocampus when ischemic postconditioning. To reveal the effect and possible mechanism of rCBF when hippocampus microenvironment is changed by aminoglutaminic acid、calcium ion.Then provide important base for theory and experiment on the protection of brain on ischemic condition.METHODS: To individually establish photochemical induction cerebral ischemic model (thrombotic cerebral ischemia)、middle cerebral artery occlusion model (occlusive cerebral ischemia) in tree shrews,then 3 circulations 5min on/5min off on arteriae carotis communis is ischemic postconditioning.To observe change of rCBF in different time(including 4、8、12、24、72h after cerebral ischemia ),and timing execute animals.The absorbance of neuron VEGF expression in hippocampus CA1 area was detected by immunochemistry in 4、8、12、24、72h after cerebral ischemic,using high definition image analysis.The ultramicrostructure of mitochondrion ,endoplasmic reticulum change in hippocampus were observed with electronic microscope 4、8、12、24、72h after cerebral ischemic.Then observe change of rCBF in hippocampus CA1 area through microperfusion aminoglutaminic acid (50mmol/l)、calcium ion(100umol/1) in normal hippocampus.RESULTS:The rCBF reduce along with temporal lasting in cerebral thrombus (different time vs sham P value<0．01) ,especially decrease in 24h (2．55±0．28pu) ;then add ischemic postconditioning to TC group except 4h group (P> 0．05) ,the rCBF of other groups also to a exten restoration,especially increase in 72h (18．74+1．59) ; The rCBF of MCAO group along with prolong time after cerebral ischemic (after cerebral ischemic 4、24、72h) also decrease (P<0．01) ,the same to lower in 72h (1．056±0．033) ; when apply ischemic postconditioning to MCAO group,the rCBF can be restored to same extent ,however no significant deviation (P>0．05) except 4h group (P<0．05) ; The rCBF of TC group to compare MCAO group , besides 24h no obviously change (P>0．05) , that of 4h and 72h MCAO group both lower than TC group (P<0．01) ; After PC, the rCBF of TC group and MCAO group both increase; among the total especially in TC group (P<0．01) .After cerebral ischemic 4h , expresses of VEGF in TC group gradually begin to intensification (P<0．01) , express of VEGF in 12h is the most intensification; but express of it after 24h attenuated (P<0．01) , the most attenuate in 72 h (P > 0．05 ) . Among PC+ MCAO groups besides 8h (P > 0．05) , the other groups also enhance than TC (P<0．01) , obviously in 12 h group; The expression of VEGF of MCAO group is the most increase in 24 h (P<0．01) ,but after PC the expression of VEGF is very high than before ;And observation that the expression of VEGF of TC group is obviously higer than MCAO group by ischemic postconditioning (P<0．01) . Electron microscope reveals that mitochondrium stress and endoplasmic reticulum cisterna formation of hippocampus were the most manifest in ischemic 24 h, but when we apply PC on it ,the phenomenon can be relieived; The phenomenon above-mentioned for MCAO group was the most manifest in24 h, and more Severity than TC; but can be relieived by administration PC.Then difference microperfusion 50mmol/L aminoglutaminic acid、100umol/L calcium ion in hippocampus, the rCBF of both groups significant depress than sham (P<0．01) , with approximation the rCBF of ischemic 4 h.CONCLUSION:①Our experiment firstly confirms that PC which to be enforced by deligated common carotid artery can against cerebral ischemia, among them it was better that can against thrombus ischemic model; During ischemic 12h, the high expression of VEGF maybe relate to rCBF amelioration;②Also PC influence the rCBF of hippocampus maybe the key point of protective neuron ; The interrelation between the expression of VEGF and amelioration of rCBF;③The decrease of CA1 area of hippocampus except for relevant thrombogenesis or vascular occlusion , still close relation to region elevated concentration aminoglutaminic acid and calcium ion.