Abstract
BackgroundComplex mechanisms participate in microglial activation after a traumatic brain injury (TBI). TBI can induce autophagy and apoptosis in neurons and glial cells, and moderate hypothermia plays a protective role in the acute phase of TBI. In the present study, we evaluated the effect of TBI and moderate hypothermia on microglial activation and investigated the possible roles of autophagy/apoptosis and toll-like receptor 4 (TLR4).MethodsThe TBI model was induced with a fluid percussion TBI device. Moderate hypothermia was achieved under general anesthesia by partial immersion in a water bath for 4 h. All rats were killed 24 h after the TBI.ResultsOur results showed downregulation of the microglial activation and autophagy, but upregulation of microglial apoptosis, upon post-TBI hypothermia treatment. The expression of TLR4 and downstream myeloid differentiation primary response 88 (MyD88) was attenuated. Moderate hypothermia reduced neural cell death post-TBI.ConclusionsModerate hypothermia can reduce the number of activated microglia by inhibiting autophagy and promoting apoptosis, probably through a negative modulation between autophagy and apoptosis. Moderate hypothermia may attenuate the pro-inflammatory function of microglia by inhibiting the MyD88-dependent TLR4 signaling pathway.
Highlights
Complex mechanisms participate in microglial activation after a traumatic brain injury (TBI)
We demonstrated that post-TBI hypothermia could upregulate the autophagy pathway, modulate apoptosis, and reduce cell death in neurons and glial cells; a possible mechanism for this is the negative regulatory effect of autophagy on apoptosis [7, 8]
We evaluated the effect of hypothermia on the microglial activation post-TBI and preliminarily explored the possible mechanisms, with regard to the relationship between autophagy, apoptosis, and the myeloid differentiation primary response 88 (MyD88)-dependent toll-like receptor 4 (TLR4) pathway
Summary
Complex mechanisms participate in microglial activation after a traumatic brain injury (TBI). TBI can induce autophagy and apoptosis in neurons and glial cells, and moderate hypothermia plays a protective role in the acute phase of TBI. We evaluated the effect of TBI and moderate hypothermia on microglial activation and investigated the possible roles of autophagy/apoptosis and toll-like receptor 4 (TLR4). Traumatic brain injury (TBI) is a major cause of morbidity and mortality. The pathological process of TBI is quite complicated and is commonly divided into two phases, primary and secondary injury. The activation of resident microglia plays a key pro-inflammatory role in the acute secondary phase post-TBI [1,2,3]. Toll-like receptor 4 (TLR4) is mainly expressed in microglia.
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