Microglial-derived microparticles mediate neuroinflammation after traumatic brain injury

作者：Alok Kumar, Bogdan A. Stoica, David J. Loane, Ming Yang, Gelareh Abulwerdi, Niaz Khan, Asit Kumar, Stephen R. Thom, Alan I. Faden · 发表于：Journal of Neuroinflammation · 年份：2017 · DOI：10.1186/s12974-017-0819-4 · 被引用次数：324 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Traumatic Brain Injury and Neurovascular Disturbances、Extracellular vesicles in disease

BACKGROUND: Local and systemic inflammatory responses are initiated early after traumatic brain injury (TBI), and may play a key role in the secondary injury processes resulting in neuronal loss and neurological deficits. However, the mechanisms responsible for the rapid expansion of neuroinflammation and its long-term progression have yet to be elucidated. Here, we investigate the role of microparticles (MP), a member of the extracellular vesicle family, in the exchange of pro-inflammatory molecules between brain immune cells, as well as their transfer to the systemic circulation, as key pathways of inflammation propagation following brain trauma. METHODS: Adult male C57BL/6 mice were subjected to controlled cortical impact TBI for 24 h, and enriched MP were isolated in the blood, while neuroinflammation was assessed in the TBI cortex. MP were characterized by flow cytometry, and MP content was assayed using gene and protein markers for pro-inflammatory mediators. Enriched MP co-cultured with BV2 or primary microglial cells were used for immune propagation assays. Enriched MP from BV2 microglia or CD11b-positive microglia from the TBI brain were stereotactically injected into the cortex of uninjured mice to evaluate MP-related seeding of neuroinflammation in vivo. RESULTS: As the neuroinflammatory response is developing in the brain after TBI, microglial-derived MP are released into the circulation. Circulating enriched MP from the TBI animals can activate microglia in vitro...