Changes In Dendritic Morphology And Spine Density In Hippocampal CA1Pyramidal Cells Of The Chronic Cerebral Ischemic Rat

Background and objective:Chronic cerebral ischemia is a common pathological state. Chronic cerebral ischemia exist in many cerebrovascular diseases(CVD),such as brain arteriosclerosis, vascular dementia, AD, Binswanger disease and arteriovenous malformations, with progressive cognitive impairment as the main symptoms. The hippocampus is an important part of the limbic system, involved in a number of higher nervous activity, acts of reflection, visceral activities, and regulation of biological rhythms and endocrine function of the integration of role. And the hippocampus has a close relationship with learning and memory, especially in the hippocampus CA1, neurons carry information processing, strengthening and delivery functions. Because of the uniqueness of hippocampal blood vessels and the highly ordered lamellar structure of hippocampal cells, the hippocampus is the most sensitive region to the brain ischemia,and hypoxia.Dendrites are important structures for neurons in information processing and synaptic transmission. There are many small protrusions on the surface of dendrites called dendritic spines, which are the primary postsynaptic targets of excitatory glutamatergic synapses. The length and arborization of dendrites and dendritic spines can expand the surface area of stimulation that neurons receive, and they play a crucial role in information transmission. Therefore, the dendritic morphology of hippocampal pyramidal cell and the plasticity of the structure and function ofdendritic spines are considered to be the cellular basis of learning and memory. Past a number of studies have showde that acute cerebral ischemia can lead to a series of traumatic changes of the hippocampal CA1pyramidal cells, and cause dendrites and dendritic spines of varying degrees of injury, In comparing with the acute cerebral ischemia, the alteration of dendrites with time in chronic cerebral ischemia is still not clear. In this experiment, the model of chronic cerebral ischemia was established withpermanent occlusion of the bilateral common carotid arteries (2VO) in rats, and brains were processed for Golgi staining. The changes in dendritic morphology and spine density in hippocampal CA1pyramidal cells were observed with optical microscope.Then presume the cellular mechanisms of chronic cerebral is chemia injury in the hippocampal CA1and its impact on learning and memory.Materials and methods30health SD rats (male or female) weight about320-350g, were divided randomly into two groups:the model group and the sham-operated group, every group had15rats. The rats in each group were further selected for observation at the time points of2,4and8weeks after operation. The model of chronic cerebral ischemia was established with permanent occlusion of the bilateral common carotid arteries (2VO) in rats. Respectively, in2weeks,4weeks,8weeks, the behavior of rats in each group was evaluated through the Morris water maze, then the successful modeling was selected, and brains were processed for Golgi staining. The changes in dendritic branch and length and spine density in hippocampal CA1pyramidal cells were observed with optical microscope.Results:1Ethology assessment Significantly Increased escape latency (P<0.05) and reduced number crossing the platform (P<0.01) were found2weeks after2VO in the model group, the alteration lasted for8weeks with the most significance at8weeks after2VO.2dendritic branch and length and spine density in CA1:Compared with the sham-operated group, dendritic branch and length in the model group was significantly reduced in4weeks and8weeks (P<0.01), and spine density in the model group were significantly reduced in2weeks,4weeks and8weeks (P<0.01); With prolonged ischemia, dendritic branch and length andspine density in the model group were all significantly reduced (P<0.05).Conclusion1. Chronic cerebral ischemia can lead to long-term learning and memory dysfunctions in rats, and cognitive dysfunction was significantly exacerbated along with ischemia time.2. Chronic cerebral ischemia can cause a significant reduction in dendritic branch and length and spine density, and lead to traumatic changes in dendrites and spines in hippocampal CA1pyramidal cells, which constitutes the pathophysiological basis in the progressive cognitive dysfunction.