Tau Protein In Beagle Dogs' Chronic Ischemic Cerebral White Matter Dysmyelination

To explore the expression level and effect of Tau Protein in ischemic cerebral white matter dysmylination in Beagle dogs.Chronic cerebral ischemia models were established by 4-vessel occlusion(4-VO)method in 16 adult Beagle dogs,The dogs were randomly divided into the sham operation group A and the experimental group B/C/D(n = 4).Select the lateral ventricle edge WM,observe the pathological changes in different groups by HE staining,compare the demyelination between the different groups after scoring by Luxol Fast Blue WM myelin staining.The expression level of Tau/p-Tau/NG2/CNPase/Fyn were detected by immunohistochemical method with average optical density.Analysising the relationship between each factor in each group by Pearson linear correlation analysis.Result of the study:(1)HE staining showed typical pathological changes of WM dysmyelination after chronic cerebral ischemic ? Compared with group A(1.50±0.5345),the WM demyelination severity was increased(P<0.05)in lateral ventricle of group B(2.25±0.4629)?C(2.50±0.5345)?D(2.75±0.4629)by LFB staining.(2)Compared with the group A(0.1392±0.0310),the expression level of Tau were significantly increased(P<0.05)in group B(0.2143±0.0214)? C(0.1851±0.0283)? D(0.1840±0.0461)? Compared with the group A(0.1845±0.0118),the expression level of p-Tau were significantly increased(P<0.05)in group B(0.2081±0.0171)?C(0.2119±0.0111)?D(0.2254±0.0125)?Compared with the group A(0.1470±0.0213),the expression level of NG2 were significantly increased(P<0.05)in group B(0.1769±0.0181)? C(0.1693±0.0169)? D(0.1703±0.0155)?Compared with the group A(0.2874±0.0242),the expression of CNPase was significantly decreased(P<0.05)in the lateral ventricle of group B(0.2404±0.0298)?C(0.2183±0.0132)?D(0.2178±0.0212)?Compared with the group A(0.2224±0.0487),the expression of Fyn was significantly decreased(P<0.05)in the lateral ventricle of group B(0.2011±0.0491)? C(0.1897±0.0490)? D(0.1606±0.0362)?(3)After analysising the relationship between the expression levels of each factor in each group by Spearman correlation analysis,the results indicated that Tau was positively correlated with the NG2(r=0.277,P=0.006).The expression level of Tau and p-Tau was negatively correlated with(r=-0.268,P=0.008).The expressionlevel of Tau and CNPase was negatively correlated with(r=-0.303,P=0.003).The expression level of p-Tau and CNPase was negatively correlated with(r=-0.509,P=0.001).The expression level of NG2 and CNPasewas negatively correlated with(r=-0.402,P=0.001).Conclusion of the study:1.Chronic cerebral ischemia can lead to dysmyelination of the lateral ventricles white matter.2.The increased expression of Tau may be related to the differentiation dysmaturity of oligodendrocyte progenitor cells in chronic cerebral ischemia.3.There is a positive correlation between Tau protein hyperphosphorylation and ischemia degree in chronic ischemic cerebral white matter demyelination,the hyperphosphorylation of Tau reduced Tau-Fyn binding,which leads the abnormal of glial cell contacting and early myelin formation.