Low-Dose LPS Modulates Microglia/Macrophages Phenotypic Transformation to Amplify Rehabilitation Effects in Chronic Spinal Cord Injured (CSCI) Mice

作者全名："Zhong, Juan; He, Yingxi; Zhao, Qin; Luo, Haodong; Zhang, Qing; Tian, Yu; Liu, Yuan; Yang, Ce; Yin, Ying; Yu, Lehua; Pan, Lu; Tan, Botao"

作者地址："[Zhong, Juan; He, Yingxi; Zhao, Qin; Luo, Haodong; Zhang, Qing; Tian, Yu; Yin, Ying; Yu, Lehua; Pan, Lu; Tan, Botao] Chongqing Med Univ, Affiliated Hosp 2, Dept Rehabil Med, Chongqing 400010, Peoples R China; [Liu, Yuan; Yang, Ce] Army Med Univ, Daping Hosp, Dept Special War Wound, State Key Lab Trauma Burns & Combined Injury, Chongqing 400042, Peoples R China"

通信作者："Pan, L; Tan, BT (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Rehabil Med, Chongqing 400010, Peoples R China."

来源：MOLECULAR NEUROBIOLOGY

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001154377300001

JCR分区：Q1

影响因子：5.1

年份：2024

卷号：　

期号：　

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结束页：　

文献类型：Article; Early Access

关键词：Rehabilitation; Low-dose LPS; Chronic spinal cord injury; Microglia/macrophages

摘要："Spinal cord injury (SCI) results in stalled motor function recovery under the chronic phase. One of the reasons due to the presence of ongoing inflammation. Therefore, regulating the status of immune cells may help reopen the window for neural repair, which represents a potential therapeutic target. In this study, we aimed to investigate whether this could be achieved in mice with cervical 5 crush CSCI (4 W) by utilizing a concentration of 0.5 mg/kg of lipopolysaccharide (LPS) to stimulate microglia/macrophages. Additionally, the mice underwent rehabilitation training for another 6 weeks. Our results showed that systemic injection of LPS enhanced the effects of forelimb rehabilitation training, as evaluated through single pellet grasping (SPG). Electrophysiological studies revealed the restoration of cortical drive to the injured side's forelimb muscles in the training combined with LPS group. Tract tracing studies demonstrated the reconstruction of cortical innervation to the cervical spinal cord. Furthermore, the levels of pro-inflammatory phenotype markers, such as inducible nitric oxide synthase (INOS) and CD68, decreased, while the expression of anti-inflammatory phenotype markers, including arginase 1 (ARG-1) and CD206, increased. Importantly, this phenotypic switch in microglia/macrophages was accompanied by an increase in phagocytic activity markers as indicated by BODIPY + IBA1 + staining. Collectively, our data suggests that low-dose LPS improves the effects of rehabilitation training by regulating the phenotypic transformation of microglia/macrophages in CSCI. This study provides a fresh perspective and intervention direction for the clinical treatment of chronic spinal cord injuries."

基金机构："Chongqing Municipal Science and Technology Bureau; State Key Laboratory of Trauma, Burns and Combined Injury, Department of Research Institute of Surgery, Daping Hospital, Army Military Medical University; Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University"

基金资助正文："The authors sincerely appreciate the experimental platform support of the State Key Laboratory of Trauma, Burns and Combined Injury, Department of Research Institute of Surgery, Daping Hospital, Army Military Medical University. Botao Tan and Ying Yin were supported by the Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University."