Arya Awadhesh K, Hu Bingren
Department of Neurology and Anesthesiology, Shock Trauma and Anesthesiology Research Center, University of Maryland School of Medicine, Baltimore, MD, USA.
Veterans Affairs Maryland Health Center System, Baltimore, MD, USA.
Brain Circ. 2018 Oct-Dec;4(4):165-173. doi: 10.4103/bc.bc_32_18. Epub 2018 Dec 31.
Stroke leads to inflammatory and immune response in the brain and immune organs. The gut or gastrointestinal tract is a major immune organ equipped with the largest pool of immune cells representing more than 70% of the entire immune system and the largest population of macrophages in the human body. The bidirectional communication between the brain and the gut is commonly known as brain-gut or gut-brain axis. Stroke often leads to gut dysmotility, gut microbiota dysbiosis, "leaky" gut, gut hemorrhage, and even gut-origin sepsis, which is often associated with poor prognosis. Emerging evidence suggests that gut inflammatory and immune response plays a key role in the pathophysiology of stroke and may become a key therapeutic target for its treatment. Ischemic brain tissue produces damage-associated molecular patterns to initiate innate and adaptive immune response both locally and systemically through the specialized pattern-recognition receptors (e.g., toll-like receptors). After stroke, innate immune cells including neutrophils, microglia or macrophages, mast cells, innate lymphocytes (IL-17 secreting γδ T-cell), and natural killer T-cell respond within hours, followed by the adaptive immune response through activation of T and B lymphocytes. Subpopulations of T-cells can help or worsen ischemic brain injury. Pro-inflammatory Th1, Th17, and γδ T-cells are often associated with increased inflammatory damage, whereas regulatory T-cells are known to suppress postischemic inflammation by increasing the secretion of anti-inflammatory cytokine IL-10. Although known to play a key role, research in the gut inflammatory and immune response after stroke is still in its initial stage. A better understanding of the gut inflammatory and immune response after stroke may be important for the development of effective stroke therapies. The present review will discuss recent advances in the studies of the brain-gut axis after stroke, the key issues to be solved, and the future directions.
中风会导致大脑和免疫器官发生炎症和免疫反应。肠道或胃肠道是一个主要的免疫器官，拥有最大的免疫细胞库，占整个免疫系统的70%以上，也是人体中巨噬细胞数量最多的部位。大脑与肠道之间的双向通信通常被称为脑-肠轴或肠-脑轴。中风常导致肠道运动障碍、肠道微生物群失调、“渗漏”肠、肠道出血，甚至肠道源性败血症，这些往往与预后不良有关。新出现的证据表明，肠道炎症和免疫反应在中风的病理生理学中起关键作用，可能成为其治疗的关键靶点。缺血性脑组织会产生损伤相关分子模式，通过专门的模式识别受体（如Toll样受体）在局部和全身引发先天性和适应性免疫反应。中风后，包括中性粒细胞、小胶质细胞或巨噬细胞、肥大细胞、先天性淋巴细胞（分泌IL-17的γδT细胞）和自然杀伤T细胞在内的先天性免疫细胞会在数小时内做出反应，随后通过T和B淋巴细胞的激活引发适应性免疫反应。T细胞亚群可以帮助或加重缺血性脑损伤。促炎性Th1、Th17和γδT细胞通常与炎症损伤增加有关，而调节性T细胞则通过增加抗炎细胞因子IL-10的分泌来抑制缺血后炎症。尽管已知其起关键作用，但中风后肠道炎症和免疫反应的研究仍处于初始阶段。更好地了解中风后肠道炎症和免疫反应可能对开发有效的中风治疗方法很重要。本综述将讨论中风后脑-肠轴研究的最新进展、有待解决的关键问题以及未来方向。
