| Estrogen is a kind of steroid secreted by ovary.It play a broad and important role in metabolism ,cardio-vascular ,cerebrovascular and bone growth .In perimenopausal period ,the function of ovary has decreased gradually .in defect of estrogen ,a serious of changes begin to take place ,such as disorders of metabolism ,increasing incidence rate of senile dementia and cardio-cerebro-vascular ,appearance of osteoporosis and so forth .As the number of aged individual increases ,dementia is a growing public health crisis. This is a particularly urgent problem in light of the fact that dementia has been carring heavy burden on family and society .No currently available treatment has been shown unequivocable to reverse existing deficits or arrest the disease's progression .Therefore ,it is imperative to find some of agents with more effects .Population-based epidemiologic studies have suggested that postmenopausal estrogen replacement therapy has positive effects in delaying the onset of dementia and improving cognitive deficits and potentially delaying disease progression.Through study to a large extent, It is hypothesized that several of these neuroprotective and neurotrophic mechanisms can be linked to estrogen effects : First, estrogen have some influence on blood and blood vessels. Estrogen's putative effects include decreased blood viscosity, inhibition of blood vessels injury, dilatation upon microvessels , increased cerebral blood flow with improvement of energy and oxygen transport together. Second, estrogen regulate nerve tissue directly. Estrogen's putative effects include blockage of A beta production and neurotoxicity, reducedexcitotoxicity, and direct anti-inflammation and antioxidant activity.Third, estrogen modulate neurons cellular function. Estrogen's putative effects include activation of the nuclear estrogen receptor, increased expression of the antiapoptotic factor bcl-2 and related proteins, prevented the injury-induced downregulation of bcl-2 expression, activation of mitogen activated protein kinase pathways, activation of cAMP signal transduction pathways, modulation of intracellular calcium homeostasis and so on .In sum, the mechanisms by which estrogen provide such neuroprotection are likely multifactorial, and probably depend on the type and severity of injury as well as the type and concentration of hormone present. Both genomic and nongenomic mechanisms may be involved.However, it has not been reported that whether estrogen can bring about the protective effect to Chronic cerebral hypoperfusion, the important one in great many of etiologic factors led to vascular dementia which number be only lesser than Alzheimer 's Disease in all dementia. So a research was made to try to study some of neuroprotective mechanisms of estrogen upon vascular dementia by means of observing the estrogen influence on nerve tissue and brain cognitive function of ovariectomized aging mice occluded bilateral common carotid artery permanently. In the experiment, by means of microscope and electron microscope and immunohistochemistry, the microstrure and ultrustructure and numbers of ChAT \CaBP \GABA positive neurons in front cortex and hippocampus were observed in three groups of sham operation and operation and operation treatmented by estradiol .the cognitive behavior of all rats in three groups were tested by a computerized shuttle-training case of AAR and PAR. The results are as follows:First, estrogen has been shown to attenuate neuronal death, the numbers and shape of neurons in front cortex and hippocampal CA1could be maintained to some extent in therapy group ,better than operation group and worse thansham group.Second, estrogen can richen synapse, narrow synapse gap,increase the number of synapse vesicle and enhance synapse connection. Third, the number of ChAT positive neurons could be improved and corelate with cognitive function .Fourth, estradiol therapy results in an increase of CaBP that regulate intracellular calcium homeostasis. Fifth, the exci...
|
PDF Full Text Request