Beneficial Effects of αB-Crystallin in Spinal Cord Contusion Injury
Beneficial Effects of αB-Crystallin in Spinal Cord Contusion Injury
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DOI：
10.1523/jneurosci.0923-12.2012
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发表时间：
2012-10-17
影响因子：
5.3
通讯作者：
Lopez-Vales, Ruben
中科院分区：
文献类型：
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作者：
Klopstein, Armelle;Santos-Nogueira, Eva;Lopez-Vales, Ruben
α B-晶状体蛋白是热休克蛋白家族的成员，其在几种应激相关条件下发挥细胞保护作用。最近的研究表明，α B-晶状体蛋白在多发性硬化症、脑缺血和亚历山大病的小鼠模型中发挥有益的作用。α B-晶状体蛋白是否在调节CNS创伤后的继发性损伤中起作用尚不清楚。我们在这里报告，α B-晶体蛋白介导的脊髓损伤后的保护作用。挫伤后脊髓组织中α B-晶体蛋白的水平降低。此外，在挫伤后第一周施用重组人α B-晶状体蛋白导致运动技能的持续改善和继发性组织损伤的改善。我们还提供了证据表明，重组人α B-晶状体蛋白调节损伤脊髓中的炎症反应，导致粒细胞浸润增加和炎性巨噬细胞募集减少。此外，即使在脊髓损伤后6小时开始治疗，重组人α B-晶状体蛋白的递送也促进更大的运动恢复。我们的研究结果表明，重组人α B-晶状体蛋白的管理可能是一个很好的治疗方法，用于治疗急性脊髓损伤，目前没有有效的治疗。
alpha B-crystallin is a member of the heat shock protein family that exerts cell protection under several stress-related conditions. Recent studies have revealed that alpha B-crystallin plays a beneficial role in a mouse model of multiple sclerosis, brain ischemia, and Alexander disease. Whether alpha B-crystallin plays a role in modulating the secondary damage after CNS trauma is not known. We report here that alpha B-crystallin mediates protective effects after spinal cord injury. The levels of alpha B-crystallin are reduced in spinal cord tissue following contusion lesion. In addition, administration of recombinant human alpha B-crystallin for the first week after contusion injury leads to sustained improvement in locomotor skills and amelioration of secondary tissue damage. We also provide evidence that recombinant human alpha B-crystallin modulates the inflammatory response in the injured spinal cord, leading to increased infiltration of granulocytes and reduced recruitment of inflammatory macrophages. Furthermore, the delivery of recombinant human alpha B-crystallin promotes greater locomotor recovery even when the treatment is initiated 6 h after spinal cord injury. Our findings suggest that administration of recombinant human alpha B-crystallin may be a good therapeutic approach for treating acute spinal cord injury, for which there is currently no effective treatment.