Cellular and molecular neurobiology
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Cell. Mol. Neurobiol. · Jul 2018
Toll-Like Receptor 4 Knockdown Attenuates Brain Damage and Neuroinflammation After Traumatic Brain Injury via Inhibiting Neuronal Autophagy and Astrocyte Activation.
Toll-like receptor 4 (TLR4) has been linked to various pathophysiological conditions, such as traumatic brain injury (TBI). It is reported that posttraumatic neuroinflammation is an essential event in the progression of brain injury after TBI. Recent evidences indicate that TLR4 mediates glial phagocytic activity and inflammatory cytokines production. ⋯ More importantly, an autophagy inducer, rapamycin pretreated, could partially abolish neuroprotective effects of TLR4 knockdown on TBI rats. Furthermore, TLR4 silencing markedly suppressed GFAP upregulation and improved cell hypertrophy to attenuate TBI-induced astrocyte activation. Taken together, these findings suggested that TLR4 knockdown ameliorated neuroinflammatory response and brain injury after TBI through suppressing autophagy induction and astrocyte activation.