The Expression Of HCN1and P38MAPK In Hippocampus Of Rats Following Chronic Cerebral Ischemia

Objective: To explore the expression of HCN1and p38MAPK followingchronic cerebral ischemia and the relationship between them of cognitiveimpairment caused by chronic cerebral ischemia.Methods: The permanent occlusion of bilateral common carotid arteries(2VO) was conducted in Wistar rats to produce the chronic cerebral ischemia.40rats were randomly divided into one month ischemia group and two monthischemia group, and control group were set up for both of ischemia groups. Thusthere were four groups in the research. The rats’ cognitive function of eachgroups were tested by Morris water maze on different time (1,2month) after2VO. The change of pyramidal cell in each group rats’ hippocampus CA1regionwas determined by HE staining on one month and two month. Proteinimmunoblotting were used to detect the expression of protein HCN1andp38MAPK. Immunofluorescence double-staining were used to observe thelocation of HCN1and p38MAPK.Results: The spatial learning and memory impaired after continuoushypoperfusion one month and more severe after continuous hypoperfusion twomonth. The result of detecting spatial learning and memory of rats were severein ischemia group by contrast with control group with significant differences(p<0.05). The pyramidal cell degenerated and arranged loosely, accompanied byinflammatory cell infiltration and gliosis in the same region in one month ischemia group. And the pyramidal cell in hippocampus CA1region of twomonth ischemia group presented disordered and depigmentation obviously.HCN1expressed on membrane of pyramidal cells in point and linear inhippocampus CA1region, and p38MAPK expressed in cytoplasm and nucleusin point and piece. HCN1and p38MAPK were co-location in cytoplasm near thecell membrane. The amount of HCN1decreased and of p38MAPK increased inischemia group compared with control group, and the change more notable intwo month ischemia group than one month ischemia with significancedifferences (p<0.05).Conclusions: Neurons in rats’ hippocampus CA1region were damaged by2VO; The cognitive impairment was caused by chronic cerebral ischemia;HCN1and p38MAPK co-located on pyramidal cell in rats’ hippocampus CA1region. The amount of p38MAPK increased and HCN1decreased with theischemia time. It may be one of mechanisms of the impairment of spatiallearning and memory caused by chronic cerebral ischemia.