Font Size: a A A

A Study On Immune Tolerance In Experimental And Clinical Work To Treat Traumatic Brain Injury

Posted on:2012-07-01Degree:DoctorType:Dissertation
Country:ChinaCandidate:H W ZhangFull Text:PDF
GTID:1114330335494218Subject:Surgery
Abstract/Summary:PDF Full Text Request
The brain tissue and brain-blood barrier were hurt by the violence after traumatic brain injury. And then the immune system was activated to cause secondary injury in the brain. The purpose of this study is to interfere with the immune system to block secondary damage in the brain.Part 1. Permeability of arachnoid granulations after traumaObjective:To confirm that the permeability of AGs increases after TBI. Methods:All treatments were done on 1st day and 3ld day after trauma. In trauma and control groups,0.5ml CSF was drained, and 0.5ml methylene blue solution was injected into cerebellar cistern. CSF from control and trauma group was mixed with 0.5ml methylene blue solution, and was injected into cerebellar cistern of two normal groups (group C and group D) respectively. Blood was drained to test concentration methylene blue and TNF-a. Results:Compared to the control group, concentrations of methylene blue and TNF-a were significantly higher in trauma group. In group C, concentrations of methylene blue and TNF-a increased than those in control group. In group D, concentrations of methylene blue and TNF-a increased than those in trauma group. There was no significant difference between trauma group and group D. Conclusions:TBI can lead to increased permeability of AGs, but apart from violence itself, the secondary inflammatory reaction comes to a greater role.Part 2. treatment of oral tolerance in experimental and clinical brain injury studiesObjective:Oral tolerance induced by self-CSF taken orally and its role in treatment of TBI. Methods:Rabbit models of TBI were taken lml CSF every day in the first week. CSF was injected back to the cerebellar cistern in group A immediately; the CSF was discard in group B; rabbits in group C were fed with self-CSF by a gastrotube; in group D, rabbits were injected 50ug complete Freund adjuvant into the posterier footpad after trauma, and fed self-CSF as group C. All rabbits were drained blood on 1st day,3rd day,7th day,14th day and 21st day to measure amount of WBCs, concentration of IL-1, IFN-y, IL-10, TGF-βand anti-brain antibody by ELISA method. All rabbits were killed on 21st day to get brains to test Glu and observe neurons.90 patients were randomly divided into three groups, and got lumber puncture every morning from 2nd day to 7th day.4ml CSF was drained to test concentration of protein. Group a need no further drainage, another 10ml CSF was discared in group b, but fed by intestinal tube in group c.4ml blood was drained on 1st day,3rdday,7th day,14th day and 21st day to get serum and test antibrain-antibody and count WBCs. Results:Concentrations of IL-1, IFN-y, anti-brain antibody, amount of Glu, neurodegeneration and WBCs in group B, group C, and group group D were lower than the control group (P<0.05). Concentrations of IL-10 and TGF-βwere higher than that in the control group (P<0.05), and increased the most in group C. In clinical trials, levels of anti-brain antibody and protein content of CSF were lowest in group c, which were of middle levles in group b (P<0.05). Conclusions:CSF drainage can reduce the antigen and protein in CSF, and release immunne injury of the brain; CSF taken orally can induce immune tolerance and reduce the immune damage. CSF drainage and oral tolerance were useful to treat TBI.Part 3. immune tolerance induced by cell therapy and it's effect on TBIObjective:To observe the effect of immature dendritic cells and ucMSCs on immunol reaction after TBI. Methods:Nothing in control group (group A),107 ucMSCs in group B and were 107 in imDCs in group C were injected into blood of rabbits with TBI on 1st day,2nd day and 3rd clay after TBI. All rabbits were drained biood on (?) day,3rd ay,7th day,14th day and 21st day to measure amount of WBC concentration of IL-1, IFN-y, IL-10, TGF-βand anti-brain antibody by ELISA method. All rabbits were killed on 21st day to get brains to test Glu and observe neurons. Results:In the stem cell group and dendritic cell group, concentrations of IL-i, IFN-γ, anti-brain antibody, amount of WBC in blood and Glu in brains were lower than those of control group (P<0.05), while concentrations of IL-10 and the of TGF-βhigher than those in control group (P<0.05). Conclusions:The intravenous injection of imDCs and ucMSCs can reduce the immune response and brain injury from secondary inflammation after TBI.
Keywords/Search Tags:traumatic brain injury, arachnoid granulation, methylene blue, immune tolerance, unbilical cord mesenchymal stem cell, immature dendritic cell
PDF Full Text Request
Related items