Deletion of p38α MAPK in microglia blunts trauma-induced inflammatory responses in mice

Josh M. Morganti, Danielle S. Goulding, Linda J. Van Eldik

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

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.

Original languageEnglish
Article number98
JournalJournal of Neuroinflammation
Volume16
Issue number1
DOIs
StatePublished - May 10 2019

Bibliographical note

Publisher Copyright:
© 2019 The Author(s).

Keywords

  • Chemokines
  • Cytokines
  • Kinase
  • Knockout
  • Microglia
  • Monocytes
  • Neuroinflammation
  • TBI
  • p38α

ASJC Scopus subject areas

  • General Neuroscience
  • Immunology
  • Neurology
  • Cellular and Molecular Neuroscience

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