The roles of chemokine (C-X-C motif) ligand 13 in spinal cord ischemia-reperfusion injury in rats

• Published in: Brain research Vol. 1727; p. 146489
• Main Authors: Chen, Fengshou, Li, Xiaoqian, Li, Zhe, Zhou, Yongjian, Qiang, Ziyun, Ma, Hong
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.01.2020
• Subjects: Animals; C-X-C chemokine receptor type 5; C-X-C motif ligand 13; Caspase 3 - metabolism; Chemokine CXCL13 - metabolism; Disease Models, Animal; Extracellular signal-regulated kinase; Extracellular Signal-Regulated MAP Kinases - metabolism; Interleukin-1beta - metabolism; Interleukin-6 - metabolism; MAP Kinase Signaling System; Mice; Rats; Rats, Sprague-Dawley; Receptors, CXCR5 - genetics; Receptors, CXCR5 - metabolism; Reperfusion Injury - complications; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; RNA, Small Interfering - genetics; Spinal Cord Ischemia - etiology; Spinal Cord Ischemia - metabolism; Spinal Cord Ischemia - pathology; Spinal cord ischemia-reperfusion injury; Tumor Necrosis Factor-alpha - metabolism; C-X-C motif ligand 13; Extracellular signal-regulated kinase; C-X-C chemokine receptor type 5; Spinal cord ischemia-reperfusion injury
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2019.146489

•Spinal cord ischemia-reperfusion injury (SCII) increased the expression of CXCL13.•CXCL13 protein was co-expressed with the NeuN and IBA-1 in SCII in rats.•SCII increased the expression of CXCR5, p-ERK, caspase-3, IL-6, TNF-α, IL-1β.•Silencing CXCL13 or CXCR5 protected against SCII, decreased ERK-mediated pathways. Spinal cord ischemia-reperfusion injury (SCII) remains an unresolved complication and its underlying mechanism has not been fully elucidated. In this study, we studied the role of chemokine (C-X-C motif) ligand 13 (CXCL13) in a rat model of SCII. We examined the time course and cellular distribution of CXCL13 protein in rats after SCII. The effects of siRNA targeting CXCL13 or C-X-C chemokine receptor type 5 (CXCR5) in SCII were also investigated. Neurological function, histological assessment, and disruption of the blood-spinal cord barrier (BSCB) were evaluated. The expression levels of CXCL13, CXCR5, phosphorylated extracellular signal-regulated kinase (p-ERK), caspase-3, interleukin 6 (IL-6), TNF-α, and IL-1β were determined. We found that SCII resulted in impaired hind limb function and increased the expression of CXCL13. In addition, CXCL13 expression demonstrated the most pronounced effect at 24 h after SCII. We reveal that CXCL13 protein was co-expressed with the mature neuron marker NeuN and the microglial marker IBA-1 in spinal cord tissues of model rats. SCII also increased the expression of CXCR5, p-ERK, caspase-3, IL-6, TNF-α, and IL-1β at 24 h after SCII. Pre-treatment with CXCL13 siRNA protected the rats against SCII and decreased the expression of signalling pathway proteins and proinflammatory cytokines mentioned above. CXCR5 siRNA also showed similar protective effects. These findings indicate that CXCL13 is involved in SCII. The CXCL13/CXCR5 axis promotes the development of SCII, possibly via ERK-mediated pathways. Targeting the mechanism of CXCL13 involved in the development of SCII might be a potential approach for the treatment of this condition.