White matter damage is an important contributor to long-term neurological deficit after stroke. Our previous study has shown that inhibition of CD147 ameliorates acute ischemic stroke in mice. In this study, we aimed to investigate whether inhibition of CD147 promotes white matter repair and long-term functional recovery after ischemic stroke.Male adult C57BL/6 mice were subjected to transient (1-hour) middle cerebral artery occlusion (tMCAO). Anti-CD147 function-blocking antibody (αCD147) was injected intravenously once daily for 3 days beginning 4 hours after onset of ischemia. Sensorimotor and cognitive functions were evaluated up to 28 days after stroke. We found that αCD147 treatment not only prevented neuronal and oligodendrocyte cell death in the acute phase, but also profoundly protected white matter integrity and reduced brain atrophy and tissue loss in the late phase, leading to improved sensorimotor and cognitive functions for at least 28 days after stroke. Mechanistically, we found that αCD147 treatment increased the number of proliferating NG2(+)/PDGFRα(+) oligodendrocyte precursor cells (OPCs) and newly generated mature APC(+)/Sox10(+) oligodendrocytes after stroke, possibly through upregulation of SDF-1/CXCR4 axis in OPCs. In conclusion, inhibition of CD147 promotes long-term functional recovery after stroke, at least in part, by enhancing oligodendrogenesis and white matter repair.

中文翻译：

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抑制 CD147 可改善少突胶质细胞生成并促进缺血性中风后小鼠的白质完整性和功能恢复

脑白质损伤是导致中风后长期神经功能缺损的重要因素。我们之前的研究表明，CD147 的抑制可改善小鼠的急性缺血性中风。在本研究中，我们旨在研究抑制 CD147 是否促进缺血性卒中后的白质修复和长期功能恢复。成年雄性 C57BL/6 小鼠接受短暂（1 小时）大脑中动脉闭塞 (tMCAO)。抗 CD147 功能阻断抗体 (αCD147) 在缺血开始后 4 小时开始每天静脉注射一次，持续 3 天。中风后 28 天对感觉运动和认知功能进行评估。我们发现 αCD147 治疗不仅可以防止急性期神经元和少突胶质细胞死亡，还能在晚期保护白质完整性并减少脑萎缩和组织损失，从而改善中风后至少 28 天的感觉运动和认知功能。从机制上讲，我们发现 αCD147 治疗增加了中风后增殖的 NG2(+)/PDGFRα(+) 少突胶质前体细胞 (OPCs) 和新生成的成熟 APC(+)/Sox10(+) 少突胶质细胞的数量，可能是通过上调 SDF- OPC 中的 1/CXCR4 轴。总之，CD147 的抑制至少部分是通过增强少突胶质细胞生成和白质修复来促进中风后的长期功能恢复。我们发现 αCD147 治疗增加了中风后增殖的 NG2(+)/PDGFRα(+) 少突胶质细胞 (OPCs) 和新生成的成熟 APC(+)/Sox10(+) 少突胶质细胞的数量，可能是通过上调 SDF-1/ OPC 中的 CXCR4 轴。总之，CD147 的抑制至少部分是通过增强少突胶质细胞生成和白质修复来促进中风后的长期功能恢复。我们发现 αCD147 治疗增加了中风后增殖的 NG2(+)/PDGFRα(+) 少突胶质细胞 (OPCs) 和新生成的成熟 APC(+)/Sox10(+) 少突胶质细胞的数量，可能是通过上调 SDF-1/ OPC 中的 CXCR4 轴。总之，CD147 的抑制至少部分是通过增强少突胶质细胞生成和白质修复来促进中风后的长期功能恢复。