Laboratory of Behavioral Neuroscience, National Institute On Aging. Baltimore, Baltimore, MD, USA.
Departments of Physical Therapy and Rehabilitation Science, and Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.
Mol Neurodegener. 2023 Jun 5;18(1):37. doi: 10.1186/s13024-023-00627-2.
Peripheral inflammation, defined as inflammation that occurs outside the central nervous system, is an age-related phenomenon that has been identified as a risk factor for Alzheimer's disease. While the role of chronic peripheral inflammation has been well characterized in the context of dementia and other age-related conditions, less is known about the neurologic contribution of acute inflammatory insults that take place outside the central nervous system. Herein, we define acute inflammatory insults as an immune challenge in the form of pathogen exposure (e.g., viral infection) or tissue damage (e.g., surgery) that causes a large, yet time-limited, inflammatory response. We provide an overview of the clinical and translational research that has examined the connection between acute inflammatory insults and Alzheimer's disease, focusing on three categories of peripheral inflammatory insults that have received considerable attention in recent years: acute infection, critical illness, and surgery. Additionally, we review immune and neurobiological mechanisms which facilitate the neural response to acute inflammation and discuss the potential role of the blood-brain barrier and other components of the neuro-immune axis in Alzheimer's disease. After highlighting the knowledge gaps in this area of research, we propose a roadmap to address methodological challenges, suboptimal study design, and paucity of transdisciplinary research efforts that have thus far limited our understanding of how pathogen- and damage-mediated inflammatory insults may contribute to Alzheimer's disease. Finally, we discuss how therapeutic approaches designed to promote the resolution of inflammation may be used following acute inflammatory insults to preserve brain health and limit progression of neurodegenerative pathology.
外周炎症是指发生在中枢神经系统之外的炎症，它是一种与年龄相关的现象，已被确定为阿尔茨海默病的风险因素。虽然慢性外周炎症在痴呆症和其他与年龄相关的疾病中作用已得到充分描述，但对于发生在中枢神经系统之外的急性炎症性损伤对神经系统的影响知之甚少。在这里，我们将急性炎症性损伤定义为以病原体暴露（例如病毒感染）或组织损伤（例如手术）形式发生的免疫挑战，导致大量但时间有限的炎症反应。我们概述了检查急性炎症性损伤与阿尔茨海默病之间联系的临床和转化研究，重点介绍了近年来受到广泛关注的三类外周炎症性损伤：急性感染、重病和手术。此外，我们还回顾了促进急性炎症时神经反应的免疫和神经生物学机制，并讨论了血脑屏障和神经免疫轴的其他成分在阿尔茨海默病中的潜在作用。在强调该研究领域知识空白之后，我们提出了一条路线图，以解决方法学挑战、研究设计欠佳以及跨学科研究努力不足的问题，这些问题迄今为止限制了我们对病原体和损伤介导的炎症性损伤如何可能导致阿尔茨海默病的理解。最后，我们讨论了旨在促进炎症消退的治疗方法如何在急性炎症性损伤后用于保护大脑健康并限制神经退行性病理的进展。
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