Biodistribution Of Taurine In Nude Mouse With Severe Traumatic Brain Injury And It’s Therapeutical Effect

Objective To conduct an in vivo optical imaging analysis of the metabolism and biodistribution of taurine in nude mouse with severe traumatic brain injury, to observe the expression of TauT and GF AP after brain trauma,Methods This study includes two experimental parts, one is in vivo optical imaging, the other is immunohistochemistry.32nude mice were randomly divided into normal group, sham operation group, brain trauma group, taurine treatment group. TBI models were made by fluid-percussion. All liquid used was injected via caudal vein immediately after TBI. In vivo optical imaging system was used to observe the distribution and metabolism of taurine at1,2,4,8,12and24h after injection. Then, the nude mice were executed, fluorescence Imaging of the isolated organ was conducted. The second part,48BALB/C mice were randomly divided into normal group, sham operation group and taurine treatment group. The building of TBI model and injection of taurine were the same with the in vivo optical imaging experiment.8mice of each group were executed at12h and24h after TBI. Morphology change of brain was observed by HE staining. The expression of TauT and GF AP was analysed by immumohistochemical staining.Results1.In group normal, Tau diffused in the whole body after injection, and the majority of Tau was excreted through kidney within12h, only the gallbladder with high concentration Tau. Tau in group sham still accumulated at skin incision margin24h after TBI. High intensity of Tau still accumulated at brain trauma area24h after TBI in group TBI-Tau. In group TBI-Cy7, Cy7diffused in subcutaneouse, without concentration in any organ.2. In group sham, there was no obvious damage in cellular morphology and structure. The ultrastructure of neuron and glia of group TBI-Cy7were severely destroyed. In group TBI-Tau, mild hyperemia, edema observed in traumatic brain tissue, with focal hemorrhage, and accompanied by polymorphonuclear inflammatory cells.3.12h after TBI, TauT expressed in vascular endothelial cell and several nerve cells in cerebral cortex and hippocampus of traumatic brain tissue. Compare with group sham, the TauT of group TBI was lower both in cerebral cortex and hippocampus (p<0.05). In group TAU, the TauT was remarkably higher than group TBI (p<0.05).24h after TBI, compare with group sham, there was no evident difference in cerebral cortex, and the TauT in hippocampus was remarkably lower in group TBI.4.12h after TBI, reactive astrocytes mainly limited in corpus callosum and hippocampus of brain trauma side of group TBI and TAU,24h after TBI, in group TBI and TAU, GFAP positive cells increased significantly, especially in the hippocampus. Both at12h and24h, the GFAP in group TBI and TAU was remarkably higher than group sham, and there were no significant differences between them.Conclusion1. The in vivo optical imaging technology can accurately monitor the distribution and metabolism of Tau in nude mouse. The majority of Tau was excreted through kidney. After TBI, Tau could accumulate specifically at brain trauma area and skin incision margin. The distribution of Tau in in vitro brain tissue was consistent with brain trauma area.2. Tau could effectively alleviate the damage of neural cells24h after TBI, and the ultrastructure of neuron and glia returned to normal, which showed effective therapeutic effect of Tau from morphology aspect.3. TauT expressed in vascular endothelial cell and several neural cells in cerebral cortex and hippocampus of brain trauma area. TBI could obviously inhibit expression of TauT, and exogenous Tau could promote TauT expression in cerebral cortex and hippocampus of brain trauma area.4.12h after TBI, the expression of GFAP was significantly increased in corpus callosum and hippocampus of brain trauma area, Tau could’t reduce the proliferation of glial cells in the acute phase of TBI.