Journal of neuroimmunology
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Traumatic brain injury (TBI) initiates inflammatory responses that result in an enduring cascade of secondary neuronal loss and behavioural impairment. Toll-like receptor 4 (TLR4), predominantly expressed by microglia, recognizes damage-associated molecular patterns (DAMPs) and regulates inflammatory processes. Interestingly, the switch of microglial M1/M2 phenotypes after TBI is highly important regarding damage and restoration of neurological function. ⋯ Our results demonstrate that the absence of TLR4 induces microglial polarization toward the M2 phenotype and promotes microglial migration and, in turn, alleviates the development of neuroinflammation, which indicates potential neuroprotective effects in the TBI mouse model. Furthermore, up-regulation of IL-4 expression in TLR4 KO mice could contribute to anti-inflammatory functions and promote microglial polarization toward the M2 phenotype, which might be mediated by active Rac-1 expression. Taken together, TLR4 deficiency contributes to regulating microglia to switch to the M2 phenotype, which ameliorates neurological impairment after TBI.