Secondary damage after spinal cord injury (SCI) is characterized by a cascade of events including hemorrhage, apoptosis, oxidative stress, and inflammation which increase the lesion size which can influence the functional impairment. Thus, identifying specific mechanisms attributed to secondary injury is critical in minimizing tissue damage and improving neurological outcome. In this work, we are investigating the role of CCL3 (macrophage inflammatory protein 1-α, MIP-1α), a chemokine involved in the recruitment of inflammatory cells, which plays an important role in inflammatory conditions of the central and peripheral nervous system. A mouse model of lower thoracic (T11) spinal cord contusion injury was used. We assessed expression levels of CCL3 and its receptors on the mRNA and protein level and analyzed changes in locomotor recovery and the inflammatory response in the injured spinal cord of wild-type and CCL3−/− mice. The expression of CCL3 and its receptors was increased after thoracic contusion SCI in mice. We then examined the role of CCL3 after SCI and its direct influence on the inflammatory response, locomotor recovery and lesion size using CCL3−/− mice. CCL3−/− mice showed mild but significant improvement of locomotor recovery, a smaller lesion size and reduced neuronal damage compared to wild-type controls. In addition, neutrophil numbers as well as the pro-inflammatory cytokines and chemokines, known to play a deleterious role after SCI, were markedly reduced in the absence of CCL3. We have identified CCL3 as a potential target to modulate the inflammatory response and secondary damage after SCI. Collectively, this study shows that CCL3 contributes to progressive tissue damage and functional impairment during secondary injury after SCI.

中文翻译：

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CCL3 导致脊髓损伤后继发性损伤

脊髓损伤 (SCI) 后继发性损伤的特征是一系列事件，包括出血、细胞凋亡、氧化应激和炎症，这些事件会增加病变大小，从而影响功能障碍。因此，确定归因于继发性损伤的特定机制对于最大限度地减少组织损伤和改善神经结果至关重要。在这项工作中，我们正在研究 CCL3（巨噬细胞炎症蛋白 1-α，MIP-1α）的作用，这是一种参与炎症细胞募集的趋化因子，在中枢和外周神经系统的炎症状况中起着重要作用。使用下胸椎 (T11) 脊髓挫伤的小鼠模型。我们评估了 CCL3 及其受体在 mRNA 和蛋白质水平上的表达水平，并分析了野生型和 CCL3 - / - 小鼠受伤脊髓的运动恢复和炎症反应的变化。CCL3 及其受体的表达在小鼠胸挫伤 SCI 后增加。然后，我们使用 CCL3 - / - 小鼠检查了 CCL3 在 SCI 后的作用及其对炎症反应、运动恢复和病变大小的直接影响。与野生型对照相比，CCL3 - / - 小鼠表现出轻微但显着的运动恢复改善、更小的损伤尺寸和减少的神经元损伤。此外，在没有 CCL3 的情况下，中性粒细胞数量以及已知在 SCI 后发挥有害作用的促炎细胞因子和趋化因子显着减少。我们已将 CCL3 确定为调节 SCI 后炎症反应和继发性损伤的潜在靶标。总的来说，这项研究表明 CCL3 在 SCI 后继发性损伤期间导致进行性组织损伤和功能障碍。