| Chronic cerebral hyperfusion(CCH),is the main cause of leukoaraiosis.At present,it is considered that leukoaraiosis after chronic cerebral ischemia is an important type of cerebral small vessel disease.However,the clinical characteristics,effective treatment,and the clinical indicators of leukoaraiosis after chronic cerebral ischemia are still unclear.Therefore,this paper carried out the following three aspects of research,first,to explore the clinical indicators used for drug efficacy observation of leukoaraiosis.Second,to explore the effect of nicotinamide(NAM)for CCH.Third,to explore the protection mechanism of NAM for CCH.Chapter 1: Clinical characteristics of patients with chronic cerebral ischemia and leukoaraiosisObjective: To analyze the clinical characteristics of patients with leukoaraiosis and screen out the effective observation indicators for the treatment of chronic cerebral ischemia.Methods: From January 1,2019 to December 31,2019,118 hospitalized patients with lacunar cerebral infarction(more than 3 months)were collected in Brain Hospital Affiliated to Nanjing Medical University.All patients were examined with head MRI.According to Fazekas' leukoaraiosis scale,the patients were divided into4 groups with grade 0 ? 3.The collected clinical information included name,gender,age,height,weight,smoking,drinking,hypertension,diabetes and family history.The laboratory data included: TC,TG,Hb A1 c,LDL,HDL and other biological indicators.The neurological deficit Assessment: NIHSS scale was used to assess the severity of admission,m RS scale was used to assess the degree of neurological deficit,BBS scale was used to assess balance function,MMSE scale was used to assess the degree of cognitive function,HAMA and HAMD were used to assess emotional state.SPSS16.0 statistical software was used for statistical analysis of the data,p < 0.05 was considered statistically significant.Results: There were differences in the history of hypertension and diabetes among different leukoaraiosis groups.Age and recent blood glucose control were positively correlated with the degree of leukoaraiosis.The balance function score,cognitive function score and mental state score were found to be correlated with the degree of leukoaraiosis.Logistic correlation analysis showed that balance function score and cognitive function score could be used as evaluation indexes of leukoaraiosis.Conclusion: There are neurological deficits in cognitive,emotional and balance function after leukoaraiosis.These neurological dysfunction,especially cognitive and balance dysfunction,might be used as an effective indicator for drug treatment after chronic cerebral ischemia.Chapter 2: The protective effect of NAM on neurological function injury after chronic cerebral ischemiaObjective: To detect the protective effect of NAM on chronic cerebral ischemia.Methods: 3-month-old C57 BL / 6J male mice with 8 mice in each group were divided into three groups: Sham group,CCH group and NAM group.Bilateral carotid artery stenosis(BCAS)was used to established the model of chronic cerebral ischemia.NAM(200 mg / kg)was injected intraperitoneally 2 hours after modeling.The mice were injected with the same dose of NAM every day.The balance function of mice was evaluated by rotating rod test on the 1st,3rd,7th,14 th and 30 th day after operation.The cognitive function and emotional function of mice were detected by Morris water maze test,open field test,sugar water test and forced swimming test on the 30 th day.The corpus callosum was stained by K-B / H-E on the 35 th day after operation.The CPNase and synapsin in corpus callosum were detected by histochemistry and Western blot.Results: After the 1st day of chronic cerebral ischemia,the balance function decreased,and NAM could alleviate this dysfunction from 3rd day.After 30 days of chronic cerebral ischemia,the learning and memory function of the CCH group decreased in Morris water maze test.In open field test,sugar water test,and forced swimming test,CCH group showed that the activity of the central area decreased,the sugar intake decreased,and the depression aggravated.NAM can reduce the balance function,cognitive function,and emotional function of behavioral disorders.Furthermore,NAM can reduce the white matter damage of corpus callosum caused by CCH.In histochemical and Western blotting examination,NAM can increase the expression of CPNase and synaptophysin in corpus callosum after CCH.Conclusion: NAM could improve the white matter remodeling function of corpus callosum,and reduce the white matter lesions after chronic cerebral ischemia,which has a protective effect on cognitive,emotional,and balance function.Chapter 3: The role of HMGB1 inflammatory protein in the protective effect of NAM after chronic cerebral ischemiaObjective: To study the protective mechanism of the effect of NAM after chronic cerebral ischemia.Methods: 3-month-old C57 BL / 6J male mice with 8 mice in each group were divided into three groups: Sham group,CCH group and NAM group.NAM(200 mg/ kg)was injected intraperitoneally after operation,and then the same dose of NAM was injected every day.The blood flow in the cortex after chronic cerebral ischemia was detected by laser speckle flowmeter before operation,1day,3 days,7 days,14 days and 30 days after operation.Evans blue test was performed on 3 days after operation,and ZO-1,CD68,and HMGB1 / RAGE were detected by histochemistry on 3 days after operation.CD68 and HMGB1/ RAGE were detected by Western blot on 3 days after operation.Results: After chronic cerebral ischemia,the cortical blood flow decreased by 30%-40%.With the prolongation of ischemia time,the cortical blood flow gradually recovered to 75%-80%.NAM could improve the recovery of cortical blood flow.The increase of Evans blue in corpus callosum and the decreased ZO-1 positive cells in histochemistry showed BBB damaged after chronic cerebral ischemia,and NAM could alleviate the damage.The expression of CD68 and HMGB1/ RAGE in the white matter increased after chronic cerebral ischemia,while NAM decreased the expression of CD68 and HMGB1 / RAGE in the corpus callosum.Conclusion: NAM can reduce BBB damage by reducing the expression of HMGB1/ RAGE in white matter,which has protective effect after CCH. |
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