Traumatic brain injury-induced neuronal damage in the somatosensory cortex causes formation of rod-shaped microglia that promote astrogliosis and persistent neuroinflammation.

Autor: Witcher KG; Department of Neuroscience, The Ohio State University, Columbus, Ohio., Bray CE; Department of Neuroscience, The Ohio State University, Columbus, Ohio., Dziabis JE; Department of Neuroscience, The Ohio State University, Columbus, Ohio., McKim DB; Department of Neuroscience, The Ohio State University, Columbus, Ohio., Benner BN; Department of Neuroscience, The Ohio State University, Columbus, Ohio., Rowe RK; Barrow Neurological Institute at Phoenix Children's Hospital, Phoenix, Arizona.; Department of Child Health, University of Arizona College of Medicine - Phoenix, Phoenix, Arizona., Kokiko-Cochran ON; Department of Neuroscience, The Ohio State University, Columbus, Ohio.; Center for Brain and Spinal Cord Repair, The Ohio State University, Columbus, Ohio., Popovich PG; Department of Neuroscience, The Ohio State University, Columbus, Ohio.; Center for Brain and Spinal Cord Repair, The Ohio State University, Columbus, Ohio.; Institute for Behavioral Medicine Research, The Ohio State University, Columbus, Ohio., Lifshitz J; Barrow Neurological Institute at Phoenix Children's Hospital, Phoenix, Arizona.; Department of Child Health, University of Arizona College of Medicine - Phoenix, Phoenix, Arizona., Eiferman DS; Department of Surgery, The Ohio State University, Columbus, Ohio., Godbout JP; Department of Neuroscience, The Ohio State University, Columbus, Ohio.; Center for Brain and Spinal Cord Repair, The Ohio State University, Columbus, Ohio.; Institute for Behavioral Medicine Research, The Ohio State University, Columbus, Ohio.
Jazyk: angličtina
Zdroj: Glia [Glia] 2018 Dec; Vol. 66 (12), pp. 2719-2736. Date of Electronic Publication: 2018 Oct 30.
DOI: 10.1002/glia.23523
Abstrakt: Microglia undergo dynamic structural and transcriptional changes during the immune response to traumatic brain injury (TBI). For example, TBI causes microglia to form rod-shaped trains in the cerebral cortex, but their contribution to inflammation and pathophysiology is unclear. The purpose of this study was to determine the origin and alignment of rod microglia and to determine the role of microglia in propagating persistent cortical inflammation. Here, diffuse TBI in mice was modeled by midline fluid percussion injury (FPI). Bone marrow chimerism and BrdU pulse-chase experiments revealed that rod microglia derived from resident microglia with limited proliferation. Novel data also show that TBI-induced rod microglia were proximal to axotomized neurons, spatially overlapped with dense astrogliosis, and aligned with apical pyramidal dendrites. Furthermore, rod microglia formed adjacent to hypertrophied microglia, which clustered among layer V pyramidal neurons. To better understand the contribution of microglia to cortical inflammation and injury, microglia were eliminated prior to TBI by CSF1R antagonism (PLX5622). Microglial elimination did not affect cortical neuron axotomy induced by TBI, but attenuated rod microglial formation and astrogliosis. Analysis of 262 immune genes revealed that TBI caused profound cortical inflammation acutely (8 hr) that progressed in nature and complexity by 7 dpi. For instance, gene expression related to complement, phagocytosis, toll-like receptor signaling, and interferon response were increased 7 dpi. Critically, these acute and chronic inflammatory responses were prevented by microglial elimination. Taken together, TBI-induced neuronal injury causes microglia to structurally associate with neurons, augment astrogliosis, and propagate diverse and persistent inflammatory/immune signaling pathways.
(© 2018 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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