Photobiomodulation inhibits the activation of neurotoxic microglia and astrocytes by inhibiting Lcn2/JAK2-STAT3 crosstalk after spinal cord injury in male rats

Abstract Background Neurotoxic microglia and astrocytes begin to activate and participate in pathological processes after spinal cord injury (SCI), subsequently causing severe secondary damage and affecting tissue repair. We have previously reported that photobiomodulation (PBM) can promote function...

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Autores principales:	Xuankang Wang, Xin Li, Xiaoshuang Zuo, Zhuowen Liang, Tan Ding, Kun Li, Yangguang Ma, Penghui Li, Zhijie Zhu, Cheng Ju, Zhihao Zhang, Zhiwen Song, Huilin Quan, Jiawei Zhang, Xueyu Hu, Zhe Wang
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Neuroinflammation Spinal cord injury Microglia Astrocytes Lcn2 JAK2-STAT3 pathway Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/e92975b195224b12aba2a7b275bf314d
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spelling	oai:doaj.org-article:e92975b195224b12aba2a7b275bf314d2021-11-08T11:14:16ZPhotobiomodulation inhibits the activation of neurotoxic microglia and astrocytes by inhibiting Lcn2/JAK2-STAT3 crosstalk after spinal cord injury in male rats10.1186/s12974-021-02312-x1742-2094https://doaj.org/article/e92975b195224b12aba2a7b275bf314d2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12974-021-02312-xhttps://doaj.org/toc/1742-2094Abstract Background Neurotoxic microglia and astrocytes begin to activate and participate in pathological processes after spinal cord injury (SCI), subsequently causing severe secondary damage and affecting tissue repair. We have previously reported that photobiomodulation (PBM) can promote functional recovery by reducing neuroinflammation after SCI, but little is known about the underlying mechanism. Therefore, we aimed to investigate whether PBM ameliorates neuroinflammation by modulating the activation of microglia and astrocytes after SCI. Methods Male Sprague–Dawley rats were randomly divided into three groups: a sham control group, an SCI + vehicle group and an SCI + PBM group. PBM was performed for two consecutive weeks after clip-compression SCI models were established. The activation of neurotoxic microglia and astrocytes, the level of tissue apoptosis, the number of motor neurons and the recovery of motor function were evaluated at different days post-injury (1, 3, 7, 14, and 28 days post-injury, dpi). Lipocalin 2 (Lcn2) and Janus kinase-2 (JAK2)-signal transducer and activator of transcription-3 (STAT3) signaling were regarded as potential targets by which PBM affected neurotoxic microglia and astrocytes. In in vitro experiments, primary microglia and astrocytes were irradiated with PBM and cotreated with cucurbitacin I (a JAK2-STAT3 pathway inhibitor), an adenovirus (shRNA-Lcn2) and recombinant Lcn2 protein. Results PBM promoted the recovery of motor function, inhibited the activation of neurotoxic microglia and astrocytes, alleviated neuroinflammation and tissue apoptosis, and increased the number of neurons retained after SCI. The upregulation of Lcn2 and the activation of the JAK2-STAT3 pathway after SCI were suppressed by PBM. In vitro experiments also showed that Lcn2 and JAK2-STAT3 were mutually promoted and that PBM interfered with this interaction, inhibiting the activation of microglia and astrocytes. Conclusion Lcn2/JAK2-STAT3 crosstalk is involved in the activation of neurotoxic microglia and astrocytes after SCI, and this process can be suppressed by PBM.Xuankang WangXin LiXiaoshuang ZuoZhuowen LiangTan DingKun LiYangguang MaPenghui LiZhijie ZhuCheng JuZhihao ZhangZhiwen SongHuilin QuanJiawei ZhangXueyu HuZhe WangBMCarticleNeuroinflammationSpinal cord injuryMicrogliaAstrocytesLcn2JAK2-STAT3 pathwayNeurology. Diseases of the nervous systemRC346-429ENJournal of Neuroinflammation, Vol 18, Iss 1, Pp 1-20 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neuroinflammation Spinal cord injury Microglia Astrocytes Lcn2 JAK2-STAT3 pathway Neurology. Diseases of the nervous system RC346-429
spellingShingle	Neuroinflammation Spinal cord injury Microglia Astrocytes Lcn2 JAK2-STAT3 pathway Neurology. Diseases of the nervous system RC346-429 Xuankang Wang Xin Li Xiaoshuang Zuo Zhuowen Liang Tan Ding Kun Li Yangguang Ma Penghui Li Zhijie Zhu Cheng Ju Zhihao Zhang Zhiwen Song Huilin Quan Jiawei Zhang Xueyu Hu Zhe Wang Photobiomodulation inhibits the activation of neurotoxic microglia and astrocytes by inhibiting Lcn2/JAK2-STAT3 crosstalk after spinal cord injury in male rats
description	Abstract Background Neurotoxic microglia and astrocytes begin to activate and participate in pathological processes after spinal cord injury (SCI), subsequently causing severe secondary damage and affecting tissue repair. We have previously reported that photobiomodulation (PBM) can promote functional recovery by reducing neuroinflammation after SCI, but little is known about the underlying mechanism. Therefore, we aimed to investigate whether PBM ameliorates neuroinflammation by modulating the activation of microglia and astrocytes after SCI. Methods Male Sprague–Dawley rats were randomly divided into three groups: a sham control group, an SCI + vehicle group and an SCI + PBM group. PBM was performed for two consecutive weeks after clip-compression SCI models were established. The activation of neurotoxic microglia and astrocytes, the level of tissue apoptosis, the number of motor neurons and the recovery of motor function were evaluated at different days post-injury (1, 3, 7, 14, and 28 days post-injury, dpi). Lipocalin 2 (Lcn2) and Janus kinase-2 (JAK2)-signal transducer and activator of transcription-3 (STAT3) signaling were regarded as potential targets by which PBM affected neurotoxic microglia and astrocytes. In in vitro experiments, primary microglia and astrocytes were irradiated with PBM and cotreated with cucurbitacin I (a JAK2-STAT3 pathway inhibitor), an adenovirus (shRNA-Lcn2) and recombinant Lcn2 protein. Results PBM promoted the recovery of motor function, inhibited the activation of neurotoxic microglia and astrocytes, alleviated neuroinflammation and tissue apoptosis, and increased the number of neurons retained after SCI. The upregulation of Lcn2 and the activation of the JAK2-STAT3 pathway after SCI were suppressed by PBM. In vitro experiments also showed that Lcn2 and JAK2-STAT3 were mutually promoted and that PBM interfered with this interaction, inhibiting the activation of microglia and astrocytes. Conclusion Lcn2/JAK2-STAT3 crosstalk is involved in the activation of neurotoxic microglia and astrocytes after SCI, and this process can be suppressed by PBM.
format	article
author	Xuankang Wang Xin Li Xiaoshuang Zuo Zhuowen Liang Tan Ding Kun Li Yangguang Ma Penghui Li Zhijie Zhu Cheng Ju Zhihao Zhang Zhiwen Song Huilin Quan Jiawei Zhang Xueyu Hu Zhe Wang
author_facet	Xuankang Wang Xin Li Xiaoshuang Zuo Zhuowen Liang Tan Ding Kun Li Yangguang Ma Penghui Li Zhijie Zhu Cheng Ju Zhihao Zhang Zhiwen Song Huilin Quan Jiawei Zhang Xueyu Hu Zhe Wang
author_sort	Xuankang Wang
title	Photobiomodulation inhibits the activation of neurotoxic microglia and astrocytes by inhibiting Lcn2/JAK2-STAT3 crosstalk after spinal cord injury in male rats
title_short	Photobiomodulation inhibits the activation of neurotoxic microglia and astrocytes by inhibiting Lcn2/JAK2-STAT3 crosstalk after spinal cord injury in male rats
title_full	Photobiomodulation inhibits the activation of neurotoxic microglia and astrocytes by inhibiting Lcn2/JAK2-STAT3 crosstalk after spinal cord injury in male rats
title_fullStr	Photobiomodulation inhibits the activation of neurotoxic microglia and astrocytes by inhibiting Lcn2/JAK2-STAT3 crosstalk after spinal cord injury in male rats
title_full_unstemmed	Photobiomodulation inhibits the activation of neurotoxic microglia and astrocytes by inhibiting Lcn2/JAK2-STAT3 crosstalk after spinal cord injury in male rats
title_sort	photobiomodulation inhibits the activation of neurotoxic microglia and astrocytes by inhibiting lcn2/jak2-stat3 crosstalk after spinal cord injury in male rats
publisher	BMC
publishDate	2021
url	https://doaj.org/article/e92975b195224b12aba2a7b275bf314d
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Photobiomodulation inhibits the activation of neurotoxic microglia and astrocytes by inhibiting Lcn2/JAK2-STAT3 crosstalk after spinal cord injury in male rats

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