Department of Physical Therapy and Rehabilitation Science, University of California, San Francisco, CA, USA; Brain and Spinal Injury Center, University of California, San Francisco, CA, USA.
Axe Neurosciences, CRCHU de Québec-Université Laval, Québec, QC, Canada.
Brain Behav Immun. 2021 Nov;98:122-135. doi: 10.1016/j.bbi.2021.08.210. Epub 2021 Aug 14.
Traumatic brain injury (TBI) is one of the leading causes of long-term neurological disability in the world. Currently, there are no therapeutics for treating the deleterious consequences of brain trauma; this is in part due to a lack of complete understanding of cellular processes that underlie TBI-related pathologies. Following TBI, microglia, the brain resident immune cells, turn into a "reactive" state characterized by the production of inflammatory mediators that contribute to the development of cognitive deficits. Utilizing multimodal, state-of-the-art techniques that widely span from ultrastructural analysis to optogenetic interrogation of circuit function, we investigated the reactive microglia phenotype one week after injury when learning and memory deficits are also measured. Microglia displayed increased: (i) phagocytic activity in vivo, (ii) synaptic engulfment, (iii) increased neuronal contact, including with dendrites and somata (termed 'satellite microglia'). Functionally, satellite microglia might impact somatic inhibition as demonstrated by the associated reduction in inhibitory synaptic drive. Cumulatively, here we demonstrate novel microglia-mediated mechanisms that may contribute to synaptic loss and cognitive impairment after traumatic brain injury.
创伤性脑损伤（TBI）是全球导致长期神经功能障碍的主要原因之一。目前，尚无治疗脑创伤有害后果的疗法；部分原因是缺乏对导致 TBI 相关病变的细胞过程的全面了解。TBI 后，大脑驻留免疫细胞小胶质细胞转变为“反应性”状态，其特征是产生炎症介质，导致认知缺陷的发展。我们利用多种先进的技术，从超微结构分析到对电路功能的光遗传询问，广泛研究了损伤后一周时的反应性小胶质细胞表型，此时也测量了学习和记忆缺陷。小胶质细胞表现出增加：（i）体内吞噬活性，（ii）突触吞噬，（iii）增加神经元接触，包括与树突和胞体（称为“卫星小胶质细胞”）的接触。功能上，卫星小胶质细胞可能会影响体细胞抑制，如相关抑制性突触驱动的减少所证明的那样。总之，我们在这里证明了新的小胶质细胞介导的机制，这些机制可能导致创伤性脑损伤后的突触丢失和认知障碍。
