Effect Of 17β-estrogen On Cognitive Function And The Expression Of NFG,BDNF,GDNF In Vascular Dementia Rats

Vascular dementia (VD) was the intellectual injury syndrome, induced by cerebrovascular diseases. It was proved that ischemia was major cause. VD was the most frequent in Asia and many developing countries according to cpidemiological study. The higher the incidence of cerebrovascular disease, the more VD patients. VD was seriously endangering man s health and life quality. Recent study show estrogen can ameliorate ischemia damage and improve cognitive function. But the protective mechanism hasn't been known. In recent years, the neuroprotection of NGF, BDNF and GDNF during ischemia brain injury has been caused attention. Studies have shown the expression of NGF, BDNF and GDNF was up-regulated following cerebral ischemia, which was able to protect neurons from ischemia injury. As to treatment of VD, the relationship of estrogen and NGF, BDNF and GDNF has not been reported. The aim of this experiment is to test NFG, BDNF and GDNF production and cognitive function change after chronic cerebral ischemia, study the mechenisms of 17β-estrogen preventing and curing chronic cerebral ischemia and prove experimental proof for 17β-estrogen preventing and curing VD. Materials and Methods.48 healthy old Wistar rats weighing from 550-650 grams and 12-13 months wererandomly divided into 3 groups. Group A were sham-operated, Group B were chronic forebrain ischemia, Group C were chronic forebrain ischemia plus 17β-estrogen. Each group was 16 respectively. Model rats of chronic forebrain ischemia were subjected to permanent bilateral common carotid arteries ligation for 2 months. The rats of three groups were intra-abdomina infused with oil, oil and 17β-estrogen respectively after operation. Cognitive function of total rats was observed at 60d after operation by Y-maze test. Then all of rats were killed. Each group divided 2 subgroup randomly. One subgroup rats were killed to make brain histological section. The section were stained with hemotoxylineosin (H.E). Histological changes of brains were examined under hight microscopre. The expression of NGF, BDNF and GDNF was analyzed by immunohistochemical method. Other subgroup rats were killed and measured the content of NGF and BDNF by ELISA method. Results1. The number of learing, the correct times for 10 maze tests of VD rats at 60d after ligation were significantly different from those of the normal rats P<0.05.(results of group A were 44.125±2.167 and 8.375 ± 1.061; results of group B are 79.870±2.695 and 5.125 ± 1.126) Significant recovery of cognitive impairment was found in VD rats infused with 17β-estrogen after 60d.(results of group C were 55.750±2.605 and 7.500±1.069)2. Examined under microscope, group B was found shrinkage and deformation of neuron bodies and concentration of nucleus and cytoplasm. Edema in brain interstitial space was obvious. Cell count of CA1 in hippocampus was decreased. In group C, most of neurons were complete in their stuctures and their shapes. Edema in brain interatitial space was light. No ischemia changes were found in group A.3. The expressions of NGF BDNF and GDNF of VD rats in hippocampus were significantly increased at 60d after ligation, P<0.05, compared with group A. (results of group A were 45.125 ± 2.417; 64.250 ± 3.772; 32.50 ± 4.928 respectively; results of group B were 60.250+5.285; 80.375 + 2.659; 58.122 + 4.343 respectively)The expression of NGF, BDNF and GDNF in the group Cwere significantly higher than those of the group B, P<0.05.( (results of group C were 83.257±4.340; 90.810±4.713; 77.134±5.055 respectively ) 4. The contents of NGF and BDNF in group B were higher than that in group A, P< 0.05;( (results of group A were 13.363 ±2.594 and 18.875 ± 3.903; results of group B were 20.838±4.193 and 28.690±2.484) The contents of NGF and BDNF in group C were significantly higher than that in group B, P<0.05. (results of group C were 30.988±4.541 and 37.174±3.878) Conclusion:1. The increase in NGF, BDNF and GDNF contents on VD rats indicated that they may play an important role in protecting ischemia cerebral tissue.2. 17β-estrogen effectively improved cognitive function, attenuated the pathological changes and possessed protective effect on VD rats3. 17β-estrogen exactly increased the expression of NGF, BDNF and GDNF in the VD rats. It may be a kind of new mechenisms of 17β-estrogen preventing and curing chronic cerebral ischemia.4. The study could be served as an experimental proof for 17β-estrogen preventing and curing VD injury. Meantime, it could be served as an theorial proof for phytoestrogon preventing and curing VD injury.