Abstract

Once excessive, neurological disorders associated with inflammatory conditions will inevitably cause secondary inflammatory damage to brain tissue. Immunosuppressive therapy can reduce the inflammatory state, but resulting infections can expose the patient to greater risk. Using specific immune tolerance organs or tissues from the body, brain antigen immune tolerance treatment can create a minimal immune response to the brain antigens that does not excessively affect the body's immunity. However, commonly used immune tolerance treatment approaches, such as those involving the nasal, gastrointestinal mucosa, thymus or liver portal vein injections, affect the clinical conversion of the therapy due to uncertain drug absorption, or inconvenient routes of administration. If hepatic portal intravenous injections of brain antigens could be replaced by normal peripheral venous infusion, the convenience of immune tolerance treatment could certainly be greatly increased. We attempted to encapsulate brain antigens with minimally immunogenic nanomaterials, to control the sizes of nanoparticles within the range of liver Kupffer cell phagocytosis and to coat the antigens with a coating material that had an affinity for liver cells. We injected these liver drug-loaded nanomaterials via peripheral intravenous injection. With the use of microparticles with liver characteristics, the brain antigens were transported into the liver out of the detection of immune armies in the blood. This approach has been demonstrated in rat models of surgical brain injury. It has been proven that the immune tolerance of brain antigens can be accomplished by peripheral intravenous infusion to achieve the effect of treating brain trauma after operations, which simplifies the clinical operation and could elicit substantial improvements in the future.

Highlights

  • The central nervous system (CNS) is commonly considered to be an immunologically privileged organ that is isolated from the immune system by the blood-brain barrier [1, 2]

  • TEM revealed that the polyvinyl alcohol (PVA)/PBAE/poly lactic-co-glycolic acid (PLGA)/MBP and PVA/PBAE/PLGA/brain protein nanoparticles exhibited regular sphere and typical “coreshell” structures (Figure 1B)

  • Neurosurgery, spontaneous cerebrospinal meningitis, etc. will expose brain antigens to the immune system due to the destruction of the blood-brain barrier, which leads to an attack by the autoimmune system that further aggravates brain tissue damage

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Summary

Introduction

The central nervous system (CNS) is commonly considered to be an immunologically privileged organ that is isolated from the immune system by the blood-brain barrier [1, 2]. Disruption of the blood-brain barrier caused by a neurosurgical operation can result in an inflammatory reaction in the CNS, which is known as a surgical brain injury (SBI) [3]. Our team performed oral brain antigen tests to establish immune tolerance for the treatment of traumatic brain injury [7]. We began to apply the idea of transplantation surgery for the thymic and liver immune tolerance approach and performed thymus injections of brain antigens to establish an immune tolerance treatment for traumatic brain injury [9]. Following the injection of brain antigen into the rat thymus to establish immune tolerance, rat spleen cells were cocultured with BV-2 microglia cells [10]. Reducing the difficulty of this operation has become a new research goal of this project

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