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

Journal of Neuroinflammation

Zhihao Zhang¹  Tan Ding²  Cheng Ju²  Zhijie Zhu²  Xueyu Hu²  Jiawei Zhang²  Penghui Li²  Huilin Quan²  Xiaoshuang Zuo²  Zhuowen Liang²  Kun Li²  Xuankang Wang²  Zhiwen Song²  Zhe Wang²  Yangguang Ma²  Xin Li³ 

[1]967 Hospital of People’s Liberation Army Joint Logistic Support Force, 116044, Dalian, Liaoning, China

[2]Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, 710032, Xi’an, Shaanxi, China

[3]Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, 710032, Xi’an, Shaanxi, China

[4]967 Hospital of People’s Liberation Army Joint Logistic Support Force, 116044, Dalian, Liaoning, China

关键词: Neuroinflammation;    Spinal cord injury;    Microglia;    Astrocytes;    Lcn2;    JAK2-STAT3 pathway;   

DOI  :  10.1186/s12974-021-02312-x

来源: Springer

【 摘 要 】

BackgroundNeurotoxic 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.MethodsMale 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.ResultsPBM 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.ConclusionLcn2/JAK2-STAT3 crosstalk is involved in the activation of neurotoxic microglia and astrocytes after SCI, and this process can be suppressed by PBM.

【 授权许可】

CC BY