Au Ngan Pan Bennett, Ma Chi Him Eddie
Department of Biomedical Sciences, City University of Hong KongKowloon Tong, Hong Kong.
Centre for Biosystems, Neuroscience, and Nanotechnology, City University of Hong KongKowloon Tong, Hong Kong.
Front Aging Neurosci. 2017 May 4;9:128. doi: 10.3389/fnagi.2017.00128. eCollection 2017.
Microglia are the resident immune cells of the central nervous system (CNS) and they contribute to primary inflammatory responses following CNS injuries. The morphology of microglia is closely associated with their functional activities. Most previous research efforts have attempted to delineate the role of ramified and amoeboid microglia in the pathogenesis of neurodegenerative diseases. In addition to ramified and amoeboid microglia, bipolar/rod-shaped microglia were first described by Franz Nissl in 1899 and their presence in the brain was closely associated with the pathology of infectious diseases and sleeping disorders. However, studies relating to bipolar/rod-shaped microglia are very limited, largely due to the lack of appropriate and experimental models. Recent studies have reported the formation of bipolar/rod-shaped microglia trains in models of CNS injury, including diffuse brain injury, focal transient ischemia, optic nerve transection and laser-induced ocular hypertension (OHT). These bipolar/rod-shaped microglia formed end-to-end alignments in close proximity to the adjacent injured axons, but they showed no interactions with blood vessels or other types of glial cell. Recent studies have also reported on a highly reproducible culture model system to enrich bipolar/rod-shaped microglia that acts as a powerful tool with which to characterize this form of microglia. The molecular aspects of bipolar/rod-shaped microglia are of great interest in the field of CNS repair. This review article focuses on studies relating to the morphology and transformation of microglia into the bipolar/rod-shaped form, along with the differential gene expression and spatial distribution of bipolar/rod-shaped microglia in normal and pathological CNSs. The spatial arrangement of bipolar/rod-shaped microglia is crucial in the reorganization and remodeling of neuronal and synaptic circuitry following CNS injuries. Finally, we discuss the potential neuroprotective roles of bipolar/rod-shaped microglia, and the possibility of transforming ramified/amoeboid microglia into bipolar/rod-shaped microglia. This will be of considerable clinical benefit in the development of novel therapeutic strategies for treating various neurodegenerative diseases and promoting CNS repair after injury.
小胶质细胞是中枢神经系统（CNS）中的常驻免疫细胞，它们在CNS损伤后引发原发性炎症反应。小胶质细胞的形态与其功能活动密切相关。此前的大多数研究都试图阐明分枝状和阿米巴样小胶质细胞在神经退行性疾病发病机制中的作用。除了分枝状和阿米巴样小胶质细胞外，双极/杆状小胶质细胞最早由弗朗茨·尼斯尔于1899年描述，它们在大脑中的存在与传染病和睡眠障碍的病理学密切相关。然而，关于双极/杆状小胶质细胞的研究非常有限，这主要是由于缺乏合适的实验模型。最近的研究报告称，在CNS损伤模型中，包括弥漫性脑损伤、局灶性短暂性缺血、视神经横断和激光诱导的高眼压（OHT），会形成双极/杆状小胶质细胞链。这些双极/杆状小胶质细胞在紧邻相邻受损轴突的位置形成端对端排列，但它们与血管或其他类型的神经胶质细胞没有相互作用。最近的研究还报道了一种高度可重复的培养模型系统，用于富集双极/杆状小胶质细胞，该系统是表征这种小胶质细胞形式的有力工具。双极/杆状小胶质细胞的分子层面在CNS修复领域备受关注。这篇综述文章重点关注与小胶质细胞形态及其向双极/杆状形式转化相关的研究，以及双极/杆状小胶质细胞在正常和病理CNS中的差异基因表达和空间分布。双极/杆状小胶质细胞的空间排列在CNS损伤后神经元和突触回路的重组和重塑中至关重要。最后，我们讨论了双极/杆状小胶质细胞潜在的神经保护作用，以及将分枝状/阿米巴样小胶质细胞转化为双极/杆状小胶质细胞的可能性。这对于开发治疗各种神经退行性疾病和促进损伤后CNS修复的新型治疗策略具有相当大的临床益处。
