2019 Aug 08 – Chronic activation of microglia and astrocytes is involved in the neuroinflammatory response that follows traumatic brain injury (TBI), and may contribute to associated long-term functional deficits. Joseph El Khoury, Michael Whalen and coworkers analyzed the temporal course of changes in gene expression that characterize activated microglia after controlled cortical impact (CCI) in mice, encompassing acute and subacute timepoints [2 days and 14 days post-injury (dpi), respectively] up to the chronic period at 60 dpi. Fluorescence activated cell sorting was used to isolate microglia from the whole brain, followed by quantitative gene expression analysis by NanoString nCounter Mouse Inflammation v2 Panel. No study had characterized before the chronic stage in an established model of focal cerebral contusion. Changes in specific clusters of genes revealed a reduced ability for microglia to sense tissue damage, perform housekeeping and maintain homeostasis in the early stages following CCI, with partial recovery at 60 dpi. A transition to inflammatory responses also emerged, with a biphasic expression pattern of genes in the interferon gamma cytokine signaling pathway (proinflammatory) and of interleukin (IL) 4 and 10 (anti-inflammatory), among others. At 60 dpi, CD40 and IL-1β were among upregulated genes identified with the highest confidence: both are known to participate in inflammatory processes and have been associated to neurodegeneration. Understanding the role of microglia in TBI pathogenesis, including critical, additional research at the single cell molecular level, may ground the advancement of novel and targeted interventions.