Blaylock Russell L, Maroon Joseph
Theoretical Neurosciences, LLC Visiting Professor of Biology, Belhaven University, Jackson, MS 315 Rolling Meadows Rd, Ridgeland, MS 39157, USA.
Surg Neurol Int. 2011;2:107. doi: 10.4103/2152-7806.83391. Epub 2011 Jul 30.
Some individuals suffering from mild traumatic brain injuries, especially repetitive mild concussions, are thought to develop a slowly progressive encephalopathy characterized by a number of the neuropathological elements shared with various neurodegenerative diseases. A central pathological mechanism explaining the development of progressive neurodegeneration in this subset of individuals has not been elucidated. Yet, a large number of studies indicate that a process called immunoexcitotoxicity may be playing a central role in many neurodegenerative diseases including chronic traumatic encephalopathy (CTE). The term immunoexcitotoxicity was first coined by the lead author to explain the evolving pathological and neurodevelopmental changes in autism and the Gulf War Syndrome, but it can be applied to a number of neurodegenerative disorders. The interaction between immune receptors within the central nervous system (CNS) and excitatory glutamate receptors trigger a series of events, such as extensive reactive oxygen species/reactive nitrogen species generation, accumulation of lipid peroxidation products, and prostaglandin activation, which then leads to dendritic retraction, synaptic injury, damage to microtubules, and mitochondrial suppression. In this paper, we discuss the mechanism of immunoexcitotoxicity and its link to each of the pathophysiological and neurochemical events previously described with CTE, with special emphasis on the observed accumulation of hyperphosphorylated tau.
一些患有轻度创伤性脑损伤的人，尤其是重复性轻度脑震荡患者，被认为会发展为一种缓慢进展的脑病，其特征是具有一些与各种神经退行性疾病共有的神经病理学特征。尚未阐明解释这部分个体中进行性神经退行性变发展的核心病理机制。然而，大量研究表明，一种称为免疫兴奋性毒性的过程可能在包括慢性创伤性脑病（CTE）在内的许多神经退行性疾病中起核心作用。免疫兴奋性毒性这一术语最初由第一作者提出，用于解释自闭症和海湾战争综合征中不断演变的病理和神经发育变化，但它也可应用于多种神经退行性疾病。中枢神经系统（CNS）内的免疫受体与兴奋性谷氨酸受体之间的相互作用引发一系列事件，如大量活性氧/活性氮生成、脂质过氧化产物积累和前列腺素激活，进而导致树突回缩、突触损伤、微管损伤和线粒体抑制。在本文中，我们讨论了免疫兴奋性毒性的机制及其与先前描述的CTE的每种病理生理和神经化学事件的联系，特别强调了观察到的过度磷酸化tau的积累。
