Department of Psychology, University of Arizona, Tucson, AZ, USA.
Department of Biomedical Engineering, University of Arizona, Tucson, AZ, USA.
Brain Behav Immun. 2017 Nov;66:31-44. doi: 10.1016/j.bbi.2017.05.009. Epub 2017 May 17.
As head injuries and their sequelae have become an increasingly salient matter of public health, experts in the field have made great progress elucidating the biological processes occurring within the brain at the moment of injury and throughout the recovery thereafter. Given the extraordinary rate at which our collective knowledge of neurotrauma has grown, new insights may be revealed by examining the existing literature across disciplines with a new perspective. This article will aim to expand the scope of this rapidly evolving field of research beyond the confines of the central nervous system (CNS). Specifically, we will examine the extent to which the bidirectional influence of the gut-brain axis modulates the complex biological processes occurring at the time of traumatic brain injury (TBI) and over the days, months, and years that follow. In addition to local enteric signals originating in the gut, it is well accepted that gastrointestinal (GI) physiology is highly regulated by innervation from the CNS. Conversely, emerging data suggests that the function and health of the CNS is modulated by the interaction between 1) neurotransmitters, immune signaling, hormones, and neuropeptides produced in the gut, 2) the composition of the gut microbiota, and 3) integrity of the intestinal wall serving as a barrier to the external environment. Specific to TBI, existing pre-clinical data indicates that head injuries can cause structural and functional damage to the GI tract, but research directly investigating the neuronal consequences of this intestinal damage is lacking. Despite this void, the proposed mechanisms emanating from a damaged gut are closely implicated in the inflammatory processes known to promote neuropathology in the brain following TBI, which suggests the gut-brain axis may be a therapeutic target to reduce the risk of Chronic Traumatic Encephalopathy and other neurodegenerative diseases following TBI. To better appreciate how various peripheral influences are implicated in the health of the CNS following TBI, this paper will also review the secondary biological injury mechanisms and the dynamic pathophysiological response to neurotrauma. Together, this review article will attempt to connect the dots to reveal novel insights into the bidirectional influence of the gut-brain axis and propose a conceptual model relevant to the recovery from TBI and subsequent risk for future neurological conditions.
随着头部损伤及其后遗症成为日益引人关注的公共卫生问题，该领域的专家在阐明损伤时和此后整个恢复过程中大脑内发生的生物学过程方面取得了重大进展。鉴于我们对神经创伤的集体知识以惊人的速度增长，通过用新的视角检查跨学科的现有文献，可能会揭示新的见解。本文将旨在将这一快速发展的研究领域的范围扩展到中枢神经系统 (CNS) 之外。具体来说，我们将研究肠道-大脑轴的双向影响在创伤性脑损伤 (TBI) 发生时以及随后的数天、数月和数年内调节复杂生物学过程的程度。除了源自肠道的局部肠内信号外，人们普遍认为胃肠道 (GI) 生理学受中枢神经系统的神经支配高度调节。相反，新出现的数据表明，CNS 的功能和健康受以下三个方面的相互作用调节：1）肠道中产生的神经递质、免疫信号、激素和神经肽；2）肠道微生物组的组成；3）作为外部环境屏障的肠壁的完整性。具体到 TBI，现有的临床前数据表明，头部损伤会导致胃肠道的结构和功能损伤，但缺乏直接研究这种肠道损伤对神经元影响的研究。尽管存在这种空白，但源自受损肠道的提出的机制与已知促进 TBI 后大脑神经病理学的炎症过程密切相关，这表明肠道-大脑轴可能是降低 TBI 后慢性创伤性脑病和其他神经退行性疾病风险的治疗靶点。为了更好地了解各种外周影响如何与 TBI 后中枢神经系统的健康相关，本文还将回顾继发性生物损伤机制和对神经创伤的动态病理生理学反应。总之，这篇综述文章将试图将这些线索联系起来，揭示肠道-大脑轴的双向影响的新见解，并提出一个与 TBI 恢复和随后未来神经状况风险相关的概念模型。
