The p38α MAPK regulates microglial responsiveness to diffuse traumatic brain injury.

Bachstetter AD, Rowe RK, Kaneko M, Goulding D, Lifshitz J, Van Eldik LJ.
Journal   J Neurosci.
Species  
Analytes Measured   IL-6 , MCP-1 , RANTES
Matrix Tested   Brain homogenates
Year   2013
Volume   33
Page Numbers   6143-6153
Application   Cytokines and Chemokines
Abstract
Neuropathology after traumatic brain injury (TBI) is the result of both the immediate impact injury and secondary injury mechanisms. Unresolved post-traumatic glial activation is a secondary injury mechanism that contributes to a chronic state of neuroinflammation in both animal models of TBI and human head injury patients. We recently demonstrated, using in vitro models, that p38α MAPK signaling in microglia is a key event in promoting cytokine production in response to diverse disease-relevant stressors and subsequent inflammatory neuronal dysfunction. From these findings, we hypothesized that the p38α signaling pathway in microglia could be contributing to the secondary neuropathologic sequelae after a diffuse TBI. Mice where microglia were p38α-deficient (p38α KO) were protected against TBI-induced motor deficits and synaptic protein loss. In wild-type (WT) mice, diffuse TBI produced microglia morphological activation that lasted for at least 7 d; however, p38α KO mice failed to activate this response. Unexpectedly, we found that the peak of the early, acute phase cytokine and chemokine levels was increased in injured p38α KO mice compared with injured WT mice. The increased cytokine levels in the p38α KO mice could not be accounted for by more infiltration of macrophages or neutrophils, or increased astrogliosis. By 7 d after injury, the cytokine and chemokine levels remained elevated in injured WT mice but not in p38α KO mice. Together, these data suggest that p38α balances the inflammatory response by acutely attenuating the early proinflammatory cytokine surge while perpetuating the chronic microglia activation after TBI.

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R-PLEX Rat IL-6 Assay
IL-6 | Rat
Singleplex
U-PLEX Mouse RANTES Antibody Set
RANTES | Mouse
R-PLEX Rat MCP-1 Antibody Set
MCP-1 | Rat
R-PLEX Rat IL-6 Antibody Set
IL-6 | Rat
V-PLEX Mouse MCP-1 Kit
MCP-1 | Mouse
Singleplex
V-PLEX Mouse Cytokine 19-Plex Kit
IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12p70, IL-15, IL-17A/F, IL-27p28/IL-30, IL-33, IP-10, KC/GRO, MCP-1, MIP-1α, MIP-2, TNF-α | Mouse
Multiplex
V-PLEX Plus Mouse MCP-1 Kit
MCP-1 | Mouse
Singleplex
V-PLEX Plus Mouse Cytokine 19-Plex Kit
IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12p70, IL-15, IL-17A/F, IL-27p28/IL-30, IL-33, IP-10, KC/GRO, MCP-1, MIP-1α, MIP-2, TNF-α | Mouse
Multiplex
Cytokine Panel 1 Mouse Control Pack
IL-9, IL-15, IL-17A/F, IL-27p28/IL-30, IL-33, IP-10, MCP-1, MIP-1α, MIP-2 | Mouse
V-PLEX Plus Cytokine Panel 1 Mouse Kit
IL-9, IL-15, IL-17A/F, IL-27p28/IL-30, IL-33, IP-10, MCP-1, MIP-1α, MIP-2 | Mouse
Multiplex
V-PLEX Cytokine Panel 1 Mouse Kit
IL-9, IL-15, IL-17A/F, IL-27p28/IL-30, IL-33, IP-10, MCP-1, MIP-1α, MIP-2 | Mouse
Multiplex
U-PLEX Mouse MCP-1 Antibody Set
MCP-1 | Mouse
U-PLEX Human IL-6 Antibody Set
IL-6 | Human
U-PLEX Human MCP-1 Antibody Set
MCP-1 | Human
U-PLEX Mouse IL-6 Antibody Set
IL-6 | Mouse
V-PLEX Plus Proinflammatory Panel 2 Rat Kit
IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-10, IL-13, KC/GRO, TNF-α | Rat
Multiplex
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