Treatment of surgical brain injury by immune tolerance induced by intrathymic and hepatic portal vein injection of brain antigens

Abstract

Surgical brain injury (SBI) defines complications induced by intracranial surgery, such as cerebral edema and other secondary injuries. In our study, intrathymic and hepatic portal vein injection of allogeneic myelin basic protein (MBP) or autogeneic brain cell suspensions were administered to a standard SBI model. Serum pro-inflammatory IL-2, anti-inflammatory IL-4 concentrations and the CD4+T/CD8+T ratio were measured at 1, 3, 7, 14 and 21 d after surgery to verify the establishment of immune tolerance. Furthermore, we confirmed neuroprotective effects by evaluating neurological scores at 1, 3, 7, 14 and 21 d after SBI. Anti-Fas ligand (FasL) immunohistochemistry and TUNEL assays of brain sections were tested at 21 d after surgery. Intrathymic injections of MBP or autogeneic brain cell suspensions functioned by both suppressing secondary inflammatory reactions and improving prognoses, whereas hepatic portal vein injections of autogeneic brain cell suspensions exerted a better effect than MBP. Intrathymic and hepatic portal vein injections of MBP had equal effects on reducing secondary inflammation and improving prognoses. Otherwise, hepatic portal vein injections of autogeneic brain cell suspensions had better outcomes than intrathymic injections of autogeneic brain cell suspensions. Moreover, the benefit of injecting antigens into the thymus was outweighed by hepatic portal vein injections.

Immune Tolerance Therapy

“…In the animal model of TBI, the injection of self-CSF and self-brain-homogenate into the thymus can induce the immune tolerance of brain antigen, which has therapeutic effect. [ 12 108 109 ] We then confirmed that intrathymic injections of brain antigens can induce immune tolerance by the reeducation function of the thymus. [ 110 ] In that study, T cells were isolated from the spleens of C57BL/6 mice after intrathymic injection of MBP in the experimental group.…”

“…[ 27 ] Inducing immune tolerance to MBP can reduce the occurrence of secondary inflammation and provide neuroprotection after brain injury. [ 28 29 ]…”

“…Yang et al . [ 29 ] reported that intrathymic injection of MBP can induce immune tolerance and reduce SBI.…”

“…After cross combination, the evaluation of immune tolerance of the four groups showed that the mixed brain antigen plus liver route had the best effect. [ 29 ] The problems that need to be solved urgently are that oral immune tolerance requires a large number of antigens, approximately 100 times the dose of antigens used for nasal mucosal immune tolerance; the autologous brain tissue antigen injection pathway is limited by the amount of autologous brain tissue and CSF; the use of allogeneic brain tissue antigens or stem cells presents with infection and/or ethical issues. Therefore, according to the types of diseases and individual differences, the selection of highly effective drug types and safe administration routes to achieve individualized treatment is the development trend of immune tolerance reconstruction in the future.…”

Can the Fact That Myelin Proteins Are Old and Break down Explain the Origin of Multiple Sclerosis in Some People?

“…Aspects of B cell biology [ 31 ] and T cell interactions with respect to MS have been more extensively reviewed elsewhere [ 32 ]. Interestingly, in surgical brain injury, it has been found that immune tolerance can be induced by hepatic portal vein and intrathymic injection of MBP [ 33 ]. Possibly, in individuals who are not affected by MS, continuous exposure to low levels of modified MBP via the route depicted in Figure 4 may act in a similar manner to therapeutic administration of a causative antigen as outlined by Verhagen et al [ 34 ].…”