Study On The Cellular And Molecular Pathogenesis Of Vascular Dementia And The Effects Of Huperzine A In Mice

Vascular dementia (VD) is a kind of cerebral dysfunction caused by a series of cerebral vessel disease and is called the acquired intelligence impairment syndrome. It belnogs to the ordinary disease of neurology. With the proportion of the elderly increases in the population the incidence of cerebral vascular disease rises, its morbidity mounts year by year rapidly and brings about a heavy load to the society and family. At present, the pathogenesis of VD can not be distinct, nor is there a specific treatment. Therefore, it is significant to study the pathophysiological mechanism of VD and to look for some effective ways for the treatment of VD.The hippocampus is considered to be correlated with learning and memory. The relation of the pathological changes in the hippocampus with VD and its function caused more attention in recent years. The median eminence of the third ventricle and the area of floor between lateral recess and lateral aperture of fourth ventricle are the specific area in the circulation of cerebralspinal fluid, and the important site in the chemistric signal transduction in brain. They have the supervisal function to the immunity information molecule, and participate in the regulating of neuronal secretion and neuronal immunity to mantaining the balance of the internal environment. It is reported that there is tangling of neurofibril and accumulation of amylum in the ependyma of the ventricles in AD. But there is no report about whether it appears in VD. The intracellular concentration of calcium ([Ca2+]i) and calmodulin (CaM) and calcium/calmodulin dependent protein kinase â…¡ (CaMPKâ…¡) are always hot spots of study on the mechanism of ischemia-hypoxia damage. A lots of studies on cerebral ischemia animal model indicate that calcium over-loading and elevation of CaM and CaMPKâ…¡ in neurons might participate in the development of ischemic damage; while the Ca2+ channel antagons might hold back calcium over-loading and alleviate the ischemia damage in neurons. Lots of academicians had taken more research on the mechanism of ischemia damage and found that elevation of cyclic AMP (cAMP) and excessive expression of glutamate acid receptors in postsynapse membrane of neurons suffered with ischemia might participate in the mechanism of ischemia damage. It is reported that [Ca2+]i and cAMP in neurons are the second signal which participate in the mechanism of learning and memory. Gradually the influence of [Ca2+]i, CaM, CaMPKâ…¡, cAMP and N-methyl-D-aspartate receptor (NMDA receptor) in neurons on learning and memory cause more interesting. Studys on Alzheimers dementia (AD) animal model indicated that calcium over-loading and decrease of cAMP, expression of adenylyl cyclase (AC) and glutamate acid receptors in neurons. These achievements bring about clues to investigate the role of calcium signal transduction mechanism, NMDA receptor and cAMP in the development of VD.In the present study, dihydroergocriptine has the apparent effect to VD in past, and became the front drug to dementia; but Huperzine A is the new drug to dementia and its effect and pharmacology is in dicussion. Thus, we make the medication group with the former drugs to investigate their new pharmacology. The VD animal model was established through cerebral ischemia-reperfusion repeatly in our study. Based on the establishment of VD model, we observed pathologic change in VD mice hippocampus CA1 area and the scanning electron microscopic(SEM) characteristics of ependyma in the median eminence of the third ventricle, and inspected the expression of NMDA receptor and the level of [Ca2+]i and CaM and CaMPKâ…¡ and cAMP and the expression of AC in hippocampus, to investigate the molecular pathogenesis of VD. The establishment of VD mice model and its pathologic features of the hippocampus 331 mice were divided into the control control group (n = 66), sham-operated group(n =66), VD model group(n = 67), dihydro- ergocriptine group(n = 66), Huperzine A group(n = 66). The mice were subjected for ischemia (20 min)- repe...