Moderate hypothermia inhibits microglial activation after traumatic brain injury by modulating autophagy/apoptosis and the MyD88-dependent TLR4 signaling pathway

Abstract Background 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. In the present study, we evaluated the effe...

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Main Authors: Fengchen Zhang, Haiping Dong, Tao Lv, Ke Jin, Yichao Jin, Xiaohua Zhang, Jiyao Jiang
Format: Article
Language:English
Published: BMC 2018-09-01
Series:Journal of Neuroinflammation
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12974-018-1315-1
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author Fengchen Zhang
Haiping Dong
Tao Lv
Ke Jin
Yichao Jin
Xiaohua Zhang
Jiyao Jiang
author_facet Fengchen Zhang
Haiping Dong
Tao Lv
Ke Jin
Yichao Jin
Xiaohua Zhang
Jiyao Jiang
author_sort Fengchen Zhang
collection DOAJ
description Abstract Background 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. 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). Methods The 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. Results Our 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. Conclusions Moderate 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.
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spelling doaj.art-a237991163794d9fb8a9094a4c5f05e72022-12-22T00:33:38ZengBMCJournal of Neuroinflammation1742-20942018-09-0115111210.1186/s12974-018-1315-1Moderate hypothermia inhibits microglial activation after traumatic brain injury by modulating autophagy/apoptosis and the MyD88-dependent TLR4 signaling pathwayFengchen Zhang0Haiping Dong1Tao Lv2Ke Jin3Yichao Jin4Xiaohua Zhang5Jiyao Jiang6Department of Neurosurgery, Ren-Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Anesthesiology, Ren-Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Neurosurgery, Ren-Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Neurosurgery, Ren-Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Neurosurgery, Ren-Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Neurosurgery, Ren-Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Neurosurgery, Ren-Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityAbstract Background 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. 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). Methods The 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. Results Our 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. Conclusions Moderate 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.http://link.springer.com/article/10.1186/s12974-018-1315-1ApoptosisAutophagyMicroglial activationToll-like receptorTraumatic brain injury
spellingShingle Fengchen Zhang
Haiping Dong
Tao Lv
Ke Jin
Yichao Jin
Xiaohua Zhang
Jiyao Jiang
Moderate hypothermia inhibits microglial activation after traumatic brain injury by modulating autophagy/apoptosis and the MyD88-dependent TLR4 signaling pathway
Journal of Neuroinflammation
Apoptosis
Autophagy
Microglial activation
Toll-like receptor
Traumatic brain injury
title Moderate hypothermia inhibits microglial activation after traumatic brain injury by modulating autophagy/apoptosis and the MyD88-dependent TLR4 signaling pathway
title_full Moderate hypothermia inhibits microglial activation after traumatic brain injury by modulating autophagy/apoptosis and the MyD88-dependent TLR4 signaling pathway
title_fullStr Moderate hypothermia inhibits microglial activation after traumatic brain injury by modulating autophagy/apoptosis and the MyD88-dependent TLR4 signaling pathway
title_full_unstemmed Moderate hypothermia inhibits microglial activation after traumatic brain injury by modulating autophagy/apoptosis and the MyD88-dependent TLR4 signaling pathway
title_short Moderate hypothermia inhibits microglial activation after traumatic brain injury by modulating autophagy/apoptosis and the MyD88-dependent TLR4 signaling pathway
title_sort moderate hypothermia inhibits microglial activation after traumatic brain injury by modulating autophagy apoptosis and the myd88 dependent tlr4 signaling pathway
topic Apoptosis
Autophagy
Microglial activation
Toll-like receptor
Traumatic brain injury
url http://link.springer.com/article/10.1186/s12974-018-1315-1
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AT yichaojin moderatehypothermiainhibitsmicroglialactivationaftertraumaticbraininjurybymodulatingautophagyapoptosisandthemyd88dependenttlr4signalingpathway
AT xiaohuazhang moderatehypothermiainhibitsmicroglialactivationaftertraumaticbraininjurybymodulatingautophagyapoptosisandthemyd88dependenttlr4signalingpathway
AT jiyaojiang moderatehypothermiainhibitsmicroglialactivationaftertraumaticbraininjurybymodulatingautophagyapoptosisandthemyd88dependenttlr4signalingpathway