Moderate Hypothermia Affects Microglia Activation After Traumatic Brain Injury By Modulating Autophagy/apoptosis And TLR4 Pathway

Inflammatory response plays an important role in the secondary brain injury after traumatic brain injury(TBI)and microglia activation is the main sign of intra-cerebral inflammatory response.Moderate hypothermia treatment has a neuroprotective effect in the acute phase of TBI,but its therapeutic effect is not enough.Due to the complexity of microglia activation after TBI,the exact mechanism of this effect remains to be elucidated.Our previous studies have confirmed that TBI induces autophagy and apoptosis in neurons and glial cells.This study evaluated the effect of moderate or severe TBI and moderate hypothermia on microglia activation and investigated possible roles of autophagy/apoptosis negative regulation and toll-like receptor 4(TLR4).In this study,SD rats(clean grade)were used,and the moderate or severe TBI model was induced by fluid percussion injury(FPI),and moderate hypothermia was achieved by ice water bath for 4 hours under general anesthesia.All rats were killed at 24 h after TBI,and the autophagy/apoptosis of the microglia in the injured cortex and ipsilateral hippocampus and the related indicators of the TLR4 pathway were detected.The results of this study showed that moderate hypothermia post-TBI could reduce the number of activated microglia,inhibit autophagy and promote microglia apoptosis,which might be through the negative regulation between autophagy and apoptosis.The expression of TLR4 and downstream myeloid differentiation primary response 88(MYD88)was also down-regulated,suggesting that hypothermia attenuated the proinflammatory function of microglia by inhibiting the MyD88-dependent TLR4 signaling pathway.