Abstract
Traumatic brain injury (TBI) is a significant cause of morbidity and mortality in the USA and other developed countries worldwide. Following the initial mechanical insult, the brain’s primary innate immune effector, microglia, initiate inflammatory signaling cascades and pathophysiological responses that can lead to chronic neuroinflammation and neurodegenerative sequelae. The p38α MAPK signaling pathway in microglia is a key contributor to inflammatory responses to diverse disease-relevant stressors and injury conditions. Therefore, we tested here whether microglia p38α contributes to acute and persistent inflammatory responses induced by a focal TBI. We generated conditional cell-specific knockout of p38α in microglia using a CX3CR1 Cre-lox system, subjected the p38α knockout and wild-type mice to a controlled cortical impact TBI, and measured inflammatory responses at acute (1-day) and subacute (7-day) post-injury time points. We found that deletion of p38α in microglia only was sufficient to attenuate multiple pro-inflammatory responses following TBI, notably reducing pro-inflammatory cytokine/chemokine production and recruitment of inflammatory monocytes into the brain and preventing the persistent microglial morphological activation. These data provide strong evidence supporting a role for microglial p38α in propagation of a chronic and potentially neurotoxic pro-inflammatory environment in the brain following TBI.
Document Type
Article
Publication Date
5-10-2019
Digital Object Identifier (DOI)
https://doi.org/10.1186/s12974-019-1493-5
Funding Information
Research reported in this publication was supported by the National Institute of Neurological Disorders R01 NS093920 (LJVE).
Related Content
The datasets generated and/or analyzed during this study are available from the corresponding author on reasonable request.
Repository Citation
Morganti, Josh M.; Goulding, Danielle S.; and Van Eldik, Linda J., "Deletion of p38α MAPK in Microglia Blunts Trauma-Induced Inflammatory Responses in Mice" (2019). Sanders-Brown Center on Aging Faculty Publications. 130.
https://uknowledge.uky.edu/sbcoa_facpub/130
Notes/Citation Information
Published in Journal of Neuroinflammation, v. 16, article no. 98, p. 1-9.
© The Author(s). 2019
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.