Department of Neuroscience, Section of Human Anatomy, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168, Rome, Italy; Gemelli Science and Technology Park (GSTeP)-Organoids Research Core Facility, Fondazione Policlinico Agostino Gemelli IRCCS, Rome, Italy.
Department of Neuroscience, Section of Human Anatomy, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168, Rome, Italy.
Neurochem Int. 2024 Nov;180:105872. doi: 10.1016/j.neuint.2024.105872. Epub 2024 Oct 1.
A growing body of evidence supports the link between peripheral inflammation and impairment of neurologic functions, including mood and cognitive abilities. The pathogenic event connecting peripheral inflammation and brain dysfunction is represented by neuroinflammation, a pathogenic phenomenon that provides an important contribution to neurodegeneration and cognitive decline also in Alzheimer's, Parkinson's, Huntington's diseases, as well as in Multiple Sclerosis. It is driven by resident brain immune cells, microglia and astrocytes, that acquire an activated phenotype in response to proinflammatory molecules moving from the periphery to the brain parenchyma. Although a huge progress has been made in clarifying cellular and molecular mechanisms bridging peripheral and central inflammation, a clear picture has not been achieved so far. Therefore, experimental models are of crucial relevance to clarify knowledge gaps in this regard. Many findings demonstrate that systemic inflammation induced by pathogen-associated molecular patterns, such as lipopolysaccharide (LPS), is able to trigger neuroinflammation. Therefore, LPS-administration is widely considered a useful tool to study this phenomenon. On this basis, the present review will focus on in vivo studies based on acute and subacute effects of systemic administration of LPS, with special attention on the state of art of microglia and astrocyte response to peripheral challenge.
越来越多的证据支持外周炎症与神经功能障碍之间的联系，包括情绪和认知能力。连接外周炎症和大脑功能障碍的致病事件是神经炎症，这是一种致病现象，它对阿尔茨海默病、帕金森病、亨廷顿病以及多发性硬化症中的神经退行性变和认知能力下降也有重要贡献。它是由驻留的大脑免疫细胞，小胶质细胞和星形胶质细胞驱动的，这些细胞在对从外周向脑实质迁移的促炎分子作出反应时获得激活表型。尽管在阐明连接外周和中枢炎症的细胞和分子机制方面已经取得了巨大进展，但到目前为止还没有明确的认识。因此，实验模型对于澄清这方面的知识空白至关重要。许多研究结果表明，病原体相关分子模式（如脂多糖（LPS））引起的全身炎症能够引发神经炎症。因此，LPS 给药被广泛认为是研究这一现象的有用工具。在此基础上，本综述将重点介绍基于 LPS 全身给药的急性和亚急性作用的体内研究，特别关注小胶质细胞和星形胶质细胞对外周刺激的反应的最新进展。
