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Protective Effects Of 17-β Estrodiol On Focal Cerebral Ischemia-reperfusion Associated With The NGF And BDNF Over-Expression

Posted on:2004-08-18Degree:MasterType:Thesis
Country:ChinaCandidate:X LiFull Text:PDF
GTID:2144360095950074Subject:Neurology
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For the high incidence, motality and disability rates, cerebrovascular diseases (CVD) are seriously endangering man's health, have become one of the three death reasons in mankind. Ischemia cerebrovascular disease (ICVD) roughly make up 70% the incidence rate of stroke. Epidemic investigation showed: premenopausal women's incidence of stroke is lower than age-matched men.But postmenopausal women's incidence of stroke strikingly rised.This indicated that estrogen played an important role in ICVD. 17-β estrodiol is an important component of estrogen .It's bioactivity is the highest.NGF and BDNF can protect neuron and restore nerve function. In recent years, studies have shown that the expression of NGF and BDNF was up-regulated following cerebral ischemia, which was able to protect neurons from ischemia injury. The aim of this experiment is to study the protective effect of 17-β estrodiol against neuronal injury and the possible roles of alternation in the expression of NGF and BDNF following cerebral ischemia-reperfiision,examine infarction volumes and hitological changes after crebral ischemia, study the mechanisms of 17- β estrodiol preventing and curing cerebral ischemia injury, provide experimental proof for 17- β estrodiol preventing and curing ICVD. Materials and MethodsSeventy-two halthy Wistar rats weighing from 250-290 grams were randomlydivided into 3 groups. Group A were sham-operated. Group B were ischemia followed by reperfusion. Group C were ischemia followed by reperfusion plus 17- beta estrodiol treatment. Rat cerebral ischemia-reperfusion injury model was established with suture emboli method. Sign were observed after rats having awaken from anesthesia. Seven days prior to experiment, 17-beta estrodiol was adminstered to rats by I.P. (0.1mg/kg, once a day). The same dosage of peanut-oil was adminstered to Group B and Group C. Brain ischemia was induced by left middle cerebral artery occlusion (MCAO) for 2hours and at 3,6,12,24 hours of reperfusion all animals were killed. Infarction volume was determined by 2,3,5-triphenyterazolium chloride (TTC) staining and image analysis. The expression of NGF and BDNF was analyzed by immunohistochemical method. After 2 hours ischemia followed by 24 hours reperfusion, rats were killed to make brain histological section. The sections were stained with hemotoxylineosin (H.E). Histological changes of brains were examined under light microscope. Results1. All animals of sham operation group hadn't motor deficit. Aimals in ischemia-reperfusion injured group and estradiol treatment group showed a significant motor deficit after sugery, especially the paralysis of the right frontlimbs, some of them exhibited circuling to right while walking. Aimals in estradiol treatment group showed significant improvement in motor fuction, their behaviour score decreasing remarkably compared with ischemia-reperfusion injured group(P<0.05).2. The TTC-stained coronal brain sections showed the pale regions which represent infarcted tissue. The TTC stained section showed that infarct zones were located in the basal ganglia, subcortex and cortex of left brain. In estradiol treatment group, infarct zones were located in the basal ganglia and subcortex, few expanded to cortex. Infarction volumes were reduced significantly in estradiol treatment group, compared with ischemia-reperrusion injured groupat 24h after reperfusion(P<0.05).3. Examined under microscope , ischemia-reperfusion injured group was found shrinkage and deformation of neuron bodies and concentration of nucleus and cytoplasm. Edema in brain interstitial space was obvious. In estradiol treatment group,most of neurons were complete in their structures, and their shapes were relatively normal. Edema in brain interatitial space was light. No ischemia changes were found in sham operation group.4. In the injured cortex, NGF expression of ischemia-reperfusion injured group come to the peak at 6h after reperfusion, and then gradually declined to the level of...
Keywords/Search Tags:17-estrodiol, cerebral ischemia reperfusion, NGF, BDNF, rats
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