Figure 10.

Proposed model of the role of p38α in the microglia response to diffuse brain injury. A, In WT mice, a mild to moderate diffuse brain injury induces a reactive glia response associated with elevated inflammatory cytokines and chemokines, morphological hypertrophy, and loss of microglia spatial domains as early as 6 h after injury. The reactive glia response, which is exemplified by an “M1” proinflammatory phenotype, persists for at least 7 d after the injury. B, In the p38α KO mice, the acute phase cytokine response is elevated compared with the WT mice. However, despite the higher cytokine response, there is a failure of the microglia deficient in p38α to exhibit an acute or chronic phase morphological activation response. C, Our results suggest that p38α is a critical kinase in the detrimental inflammatory feedforward loop responsible for neuromotor deficits.