Abstract:

Abstract:Objective To investigate the damage of hippocampal neurons induced by  chronic cerebral ischemia in the rats,and to clarify its mechanism.Methods 90 healthy adult male SD rats were randomly divided into sham operation group (n＝30) and experimental group (n＝60).The chronic cerebral ischemia rat models were established by permanently ligating the common carotid arteries on both sides of the rats in experimental group.The rats in sham operation group were established by incising the  cervical median,only the common carotid arteries on both sides were separated without ligating.The rats in sham operation group and experimental group were respectively sacrificed at the  7th,14th and 21st  day after operation.At each time point 10 rats in sham operation group and 20 rats in experimental group were selected and sacrificed.Immunohistochemistry staining was used to observe the dynamic changes of the expression levels of choline acetyltransferase(ChAT) in hippocampus neurons,and TA-FE method was used to observe the dynamic changes of hippocampal microvascualr architecture.MiVnt image analytical system was used to quantitatively analyze the immunohistochemistry result,the microvessel density (MVD) and micorvessel area density (MVA) of horizontal part of hippocampus in the rats.Results Compared with sham operation group,the ChAT expression levels in hippocampus neurons of the rats in experimental group at different time points were significantly decreased（P<0.05);and with the prolongation of time,the ChAT expression levels were gradually decreased;the ChAT expression level in 14-day experimental group was significantly lower than that in 7-day experimental group（P<0.05);the ChAT expression level in 21-day experimental group was significantly lower than those in 7-day and 14-day experimental groups（P<0.05).The MVD and MVA of hippocampus of the rats in experimental group at different time points were obviously decreased compared with sham operation group（P<0.05）;the MVA was gradually decreased with the prolongation of time,and the MVA of hippocampus of the rats in 21-day and 14-day experimental groups were obviously decreased compared with 7-day experimental group（P<0.05);the MVD was gradually decreased with the prolongation of time,the MVD of hippocampus of the rats in 21-day and 14-day experimental groups was obviously decreased compared with 7-day experimental group（P<0.05);the MVD of hippocampus of the rats in 21-day experimental group was obviously decreased compared with 14-day experimental group（P<0.05).Conclusion Chronic cerebral ischemia can lead to the progressive decrease of the ChAT expression level,MVD and MVA of hippocampus of the rats  to aggravate gradually the learning and memory dysfunction,which may be one of the reasons of vascular dementia.

Key words:  , chronic cerebral ischemia, hippocampus, microvascular architecture, choline acetyltransferase