Blaylock Russell L
Theoretical Neuroscience Research, Ridgeland, United States.
Surg Neurol Int. 2025 Jan 31;16:26. doi: 10.25259/SNI_1114_2024. eCollection 2025.
Autoimmune disorders are destructive processes considered to be an attack on "self " antigens by the immune system CD-+4 T-cells that are directed toward antigens, in the case of multiple sclerosis (MS), particularly myelin antigens. Yet, there is growing evidence that the major destructive events in MS, as well as other non-central nervous system (CNS) autoimmune disorders, are much more than an immune attack on the CNS initiated by a misdirected immune system that attacks a "self " antigen or antigens by a process called molecular mimicry. Extensive evidence suggests that inflammation, in turn, initiates excitotoxicity, which is responsible for the majority of pathological findings in all stages of the disease, especially a loss of oligodendroglia (source of myelin) and axon injury in MS. Excitotoxicity also is a better explanation for progressive MS, in which the immune attack has either slowed or is halted; yet, the destructive pathology continues to progress. It also explains the destructive lesions seen in gray matter, which is essentially devoid of inflammation. It has recently been shown that most of the damage to the oligodendrocytes, as well as axonal injury, is secondary to excitotoxicity. While there is a growing appreciation that excitotoxicity plays a major role, there has been little effort to link the immune changes to the excitotoxic process, recently named immunoexcitotoxicity, even though the role of excitotoxicity has been shown to occur in the inflammatory stage in the beginning and throughout the process of the disease, particularly the chronic progressive stage. It is also known that peripheral glutamate receptors exist throughout the body, thus making the process of immunoexcitotoxicity a possible integral part of all or most autoimmune disorders in which the immune system is intimately linked to enhancing the excitotoxic process. This is of special concern now that peripheral glutamate receptors have been isolated in many peripheral tissues and are known to be fully functional.
自身免疫性疾病是一种破坏性过程，被认为是免疫系统中针对抗原的CD4 + T细胞对“自身”抗原的攻击。在多发性硬化症（MS）中，尤其是针对髓鞘抗原。然而，越来越多的证据表明，MS以及其他非中枢神经系统（CNS）自身免疫性疾病中的主要破坏性事件，远不止是免疫系统错误地攻击“自身”抗原而引发的对中枢神经系统的免疫攻击，这种攻击是通过一种称为分子模拟的过程进行的。大量证据表明，炎症反过来会引发兴奋性毒性，而兴奋性毒性是该疾病所有阶段大多数病理表现的原因，尤其是MS中少突胶质细胞（髓鞘来源）的丧失和轴突损伤。兴奋性毒性也更好地解释了进行性MS，在这种情况下，免疫攻击要么减缓要么停止；然而，破坏性病理仍在继续发展。它还解释了在基本上没有炎症的灰质中看到的破坏性病变。最近有研究表明，少突胶质细胞的大部分损伤以及轴突损伤都是兴奋性毒性的继发结果。虽然人们越来越认识到兴奋性毒性起主要作用，但几乎没有人努力将免疫变化与兴奋性毒性过程联系起来，最近这个过程被称为免疫兴奋性毒性，尽管兴奋性毒性的作用已被证明在疾病开始的炎症阶段以及整个疾病过程中都会发生，尤其是在慢性进展阶段。还已知外周谷氨酸受体存在于全身各处，因此免疫兴奋性毒性过程可能是所有或大多数自身免疫性疾病的一个组成部分，在这些疾病中，免疫系统与增强兴奋性毒性过程密切相关。鉴于外周谷氨酸受体已在许多外周组织中被分离出来并且已知具有完整功能，这一点尤其值得关注。
