Haidar Muhammad Ali, Ibeh Stanley, Shakkour Zaynab, Reslan Mohammad Amine, Nwaiwu Judith, Moqidem Yomna Adel, Sader Georgio, Nickles Rachel G, Babale Ismail, Jaffa Aneese A, Salama Mohamed, Shaito Abdullah, Kobeissy Firas
Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Biotechnology Program, School of Science and Engineering, The American University in Cairo, Cairo, Egypt.
Curr Neuropharmacol. 2022;20(11):2050-2065. doi: 10.2174/1570159X19666211202123322.
Microglia are the resident immune cells of the brain and play a crucial role in housekeeping and maintaining homeostasis of the brain microenvironment. Upon injury or disease, microglial cells become activated, at least partly, via signals initiated by injured neurons. Activated microglia, thereby, contribute to both neuroprotection and neuroinflammation. However, sustained microglial activation initiates a chronic neuroinflammatory response which can disturb neuronal health and disrupt communications between neurons and microglia. Thus, microglia-neuron crosstalk is critical in a healthy brain as well as during states of injury or disease. As most studies focus on how neurons and microglia act in isolation during neurotrauma, there is a need to understand the interplay between these cells in brain pathophysiology. This review highlights how neurons and microglia reciprocally communicate under physiological conditions and during brain injury and disease. Furthermore, the modes of microglia-neuron communication are exposed, focusing on cell-contact dependent signaling and communication by the secretion of soluble factors like cytokines and growth factors. In addition, it has been discussed that how microglia-neuron interactions could exert either beneficial neurotrophic effects or pathologic proinflammatory responses. We further explore how aberrations in microglia-neuron crosstalk may be involved in central nervous system (CNS) anomalies, namely traumatic brain injury (TBI), neurodegeneration, and ischemic stroke. A clear understanding of how the microglia-neuron crosstalk contributes to the pathogenesis of brain pathologies may offer novel therapeutic avenues of brain trauma treatment.
小胶质细胞是大脑中的常驻免疫细胞，在维持大脑微环境的稳态及日常功能中发挥着关键作用。在受到损伤或疾病侵袭时，小胶质细胞至少部分地通过受损神经元引发的信号而被激活。激活后的小胶质细胞对神经保护和神经炎症都有影响。然而，小胶质细胞的持续激活会引发慢性神经炎症反应，这可能会损害神经元健康，并破坏神经元与小胶质细胞之间的通讯。因此，小胶质细胞与神经元之间的相互作用在健康大脑以及损伤或疾病状态下都至关重要。由于大多数研究集中在神经创伤期间神经元和小胶质细胞如何单独发挥作用，因此有必要了解这些细胞在脑病理生理学中的相互作用。这篇综述重点介绍了神经元和小胶质细胞在生理条件下以及脑损伤和疾病期间如何相互交流。此外，还揭示了小胶质细胞与神经元之间的通讯方式，重点关注细胞接触依赖性信号传导以及通过细胞因子和生长因子等可溶性因子的分泌进行的通讯。此外，还讨论了小胶质细胞与神经元的相互作用如何产生有益的神经营养作用或病理性促炎反应。我们进一步探讨了小胶质细胞与神经元相互作用的异常如何可能与中枢神经系统（CNS）异常有关，即创伤性脑损伤（TBI）、神经退行性变和缺血性中风。清楚地了解小胶质细胞与神经元之间的相互作用如何导致脑部疾病的发病机制，可能为脑外伤治疗提供新的治疗途径。
