The Mechanism Of Cognitive Dysfunction Caused By Chronic Cerebral Hypoperfusion And The Study On The Treatment Of Recanalization

OBJECTIVE:To observe the Cerebral white matter and the secondary cognitive dysfunction caused by Chronic Cerebral hypoperfusion(CCH),to study the therapeutic effect of reperfusion on CCH,and the possible mechanism of reperfusion in the treatment of CCH was preliminarily speculated.METHODS:(1)CCH mice model was established by right unilateral common carotid artery operation(rUCCAO)in mice,western-blot(WB),mouse behavioral test and Diffusion Tensor Imaging(DTI)were used to observe the changes of brain tissue and cognitive function after CCH.(2)To collect the data of cognitive function,cerebral blood flow and brain imaging in patients with Carotid artery stenosis,compare the changes before and after reperfusion operation,and observe the therapeutic effect of clinical operation.(3)To establish the model of reperfusion after rUCCAO,the neuroprotective effect of reperfusion after CCH was studied by WB and IHC.(4)To establish mice model of reperfusion and to explore the possible mechanism of reperfusion in treating CCH by IF.RESULTS:(1)WB found that white matter-related protein content decreased in rUCCAO mice,mouse behavioral experiments observed that cognitive function decreased significantly in rUCCAO mice and also in DTI imaging,rUCCAO mice had obvious white matter fiber disorder,it means that during CCH,the white matter of the brain is obviously damaged.(2)From 10 patients who underwent reperfusion operation of the Carotid artery stenosis,the cognitive function of the patients was improved,and PET/MRI and DTI imaging showed some improvement in brain imaging,it was found that reperfusion had therapeutic effect on CCH-induced brain injury.(3)White matter-related protein content of reperfusion mice was found to be higher than that of rUCCAO mice,and the recovery of brain myelin sheath injury was observed by IHC method,under transmission electron microscope,the demyelinating lesion in mice was alleviated by reperfusion.(4)The deposition of aβ in the cerebral tissue matrix of rUCCAO mice was observed by IF method.The deposition of aβ in the brain of the reperfusion mice was less than that of rUCCAO mice,it is suggested that the decrease of aβ deposition may be a possible mechanism of the recovery of CCH brain injury induced by surgical reperfusion.CONCLUSION:The damage of CCH to the white matter of mouse brain was confirmed in rUCCAO mouse model,the therapeutic effect of reperfusion was observed from clinical cases,and the mouse model of reperfusion after CCH was successfully established.It was found that after reperfusion,the brain morphology of the mice improved significantly and the tissue composition recovered somewhat.The deposition of aβ in CCH mice was found to decrease after operation.It is suggested that the decrease of aβ may be the cause of recovery of CCH injury and improvement of cognitive function.