Treatment Of Surgical Brain Injury By Immune Tolerance Induced By Intrathymic Injection Of Antigens

Objective: Surgical brain injury(SBI)model was established by using SD rats and then induce immune tolerance by intrathymic injection of ovalbumin(OVA)or myelin basic protein(MBP).The therapeutic effect of bystander suppression or immune tolerance for the treatment of secondary brain injury induced by SBI was explored and compared.Methods: 32 Male SD rats(weight 270~300g)were randomly divided into four groups with 8 rats per group.OVA group: SBI+ intrathymic injection of OVA,MBP group: SBI+ intrathymic injection of MBP,Control group: SBI+ intrathymic injection of normal saline and Sham group.Serum pro-inflammatory cytokine interleukin-2(IL-2),anti-inflammatory cytokine interleukin-4(IL-4)concentrations,CD4+T/CD8+T cell ratios in blood,modified neurological severity score(MNSS)and cerebral edema volume were measured at 1,3,7,14 and 21 d after SBI.Fas L expression level and apoptosis rate of brain cells were tested respectively at 21 d after SBI.Results: 1.Establishment of immune tolerance and evaluation of therapeutic effect by intrathymic injection of OVACompared with Sham group,the concentrations of pro-inflammatory cytokine IL-2 in Control group were increased significantly at 3,7 and 14 d after SBI(P<0.05).Compared with Control group,the serum levels of pro-inflammatory cytokine IL-2 in OVA group were decreased significantly at 3,7 and 14 d after SBI(P<0.05).The serum levels of anti-inflammatory cytokine IL-4 in OVA group were increased significantly than control group at 7 and 14 d after SBI(P<0.05).The CD4+T/CD8+T cell ratios in Control group were increased significantly compared with Sham group at 3,7 and 14 d after SBI(P<0.05).Compared with Control group,the CD4+T/CD8+T cell ratios in OVA group were decreased significantly at 7,14 d after SBI(P<0.05).Fas L expression level was increased in OVA group when compared with Control group(P<0.05).Although the apoptosis rate of brain cells was increased significantly in Control group and OVA group when compared with Sham group(P<0.05),the apoptosis rate of brain cells in OVA group was decreased significantly when compared with Control group(P<0.05).Compared with Control group,the cerebral edema volume in OVA group was decreased significantly at 14,21 d after SBI(P<0.05)and the MNSS was decreased only at 14 d after SBI in OVA group(P<0.05).2.Establishment of immune tolerance and evaluation of therapeutic effect by intrathymic injection of MBP Compared with Control group,the serum levels of pro-inflammatory cytokine IL-2 were decreased and anti-inflammatory cytokine IL-4 were increased in MBP group at 3,7 and 14 d after SBI(P<0.05).Compared with Control group,the CD4+T/CD8+T cell ratios in MBP group were decreased significantly at 7,14 d after SBI(P<0.05).Fas L expression level was increased and the apoptosis rate of brain cells was decreased in MBP group when compared with Control group(P<0.05).Compared with Control group,the cerebral edema volume and the MNSS were decreased significantly at 3,7,14 and 21 d after SBI(P<0.05).Conclusion:1.Immune tolerance induced by intrathymic injection of "bystander antigen" OVA can reduce brain edema and promote the recovery of neurological function through "bystander suppression effect".Meanwhile,consistent with the previous results of our study group,intrathymic injection of brain antigen MBP also can induce immune tolerance so as to reduce brain edema,promote the recovery of neurological function.2.Although the intrathymic injection of brain antigen MBP or bystander antigen OVA can induce the same intensity of immune tolerance,the therapeutic effect of intrathymic injection of MBP in the treatment of brain injury was better than that of OVA.But the most important thing is bystander suppression effect can be used to treat secondary brain damage,autoimmune diseases,especially those are unable to identify antigens.