VX-765 reduces neuroinflammation after spinal cord injury in mice.
VX-765 reduces neuroinflammation after spinal cord injury in mice.
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VX-765 减少小鼠脊髓损伤后的神经炎症
DOI：
10.4103/1673-5374.306096
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发表时间：
2021-09
影响因子：
6.1
通讯作者：
Lü HZ
中科院分区：
文献类型：
--
作者：
Chen J;Chen YQ;Shi YJ;Ding SQ;Shen L;Wang R;Wang QY;Zha C;Ding H;Hu JG;Lü HZ
炎症是脊髓损伤后神经元损伤的主要原因。我们假设抑制caspase-1激活可能减少脊髓损伤后的神经炎症，从而对损伤的脊髓产生保护作用。采用Infinite Horizon impact建立小鼠T9挫伤脊髓模型，脊髓损伤后连续7 d给予选择性caspase-1抑制剂VX-765。结果表明：(1)VX-765抑制脊髓损伤诱导的caspase-1激活及白细胞介素-1β和白细胞介素-18分泌。(2)脊髓损伤后，M1细胞的增加主要来自于局部小胶质细胞，而非浸润性巨噬细胞。(3)促炎Th1Th17细胞在Th亚群中占优势。VX-765抑制巨噬细胞总浸润、M1巨噬细胞/小胶质细胞、Th1和Th1Th17亚群分化和细胞毒性T细胞活化；M2小胶质细胞增多；促进Th2和Treg分化。(4) VX-765减少纤维化面积，促进白质髓鞘形成，减轻运动神经元损伤，促进功能恢复。提示VX-765通过抑制caspase-1/白细胞介素-1β/白细胞介素-18，减轻脊髓损伤后神经炎症，促进神经功能恢复。这可能是治疗脊髓损伤的一种潜在策略。本研究已于2017年2月23日获蚌埠医学院爱护动物伦理委员会批准（批准号：2017-037）。
Inflammation is a major cause of neuronal injury after spinal cord injury. We hypothesized that inhibiting caspase-1 activation may reduce neuroinflammation after spinal cord injury, thus producing a protective effect in the injured spinal cord. A mouse model of T9 contusive spinal cord injury was established using an Infinite Horizon Impactor, and VX-765, a selective inhibitor of caspase-1, was administered for 7 successive days after spinal cord injury. The results showed that: (1) VX-765 inhibited spinal cord injury-induced caspase-1 activation and interleukin-1β and interleukin-18 secretion. (2) After spinal cord injury, an increase in M1 cells mainly came from local microglia rather than infiltrating macrophages. (3) Pro-inflammatory Th1Th17 cells were predominant in the Th subsets. VX-765 suppressed total macrophage infiltration, M1 macrophages/microglia, Th1 and Th1Th17 subset differentiation, and cytotoxic T cells activation; increased M2 microglia; and promoted Th2 and Treg differentiation. (4) VX-765 reduced the fibrotic area, promoted white matter myelination, alleviated motor neuron injury, and improved functional recovery. These findings suggest that VX-765 can reduce neuroinflammation and improve nerve function recovery after spinal cord injury by inhibiting caspase-1/interleukin-1β/interleukin-18. This may be a potential strategy for treating spinal cord injury. This study was approved by the Animal Care Ethics Committee of Bengbu Medical College (approval No. 2017-037) on February 23, 2017.
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影响因子：
5.6
作者：
Horiuchi H;Oshima Y;Ogata T;Morino T;Matsuda S;Miura H;Imamura T
通讯作者：
Imamura T
影响因子：
16.6
作者：
Flores J;Noël A;Foveau B;Lynham J;Lecrux C;LeBlanc AC
通讯作者：
LeBlanc AC
髓磷脂碱性蛋白激活的Th1和Th2细胞对损伤脊髓局部免疫微环境的差异作用
影响因子：
5.3
作者：
Hu, Jian-Guo;Shi, Ling-Ling;Lu, He-Zuo
通讯作者：
Lu, He-Zuo
影响因子：
4.4
作者：
Galanopoulou, Aristea S.;Mowrey, Wenzhu B.;Moshe, Solomon L.
通讯作者：
Moshe, Solomon L.
影响因子：
4.8
作者：
Ahuja, Christopher S.;Nori, Satoshi;Fehlings, Michael G.
通讯作者：
Fehlings, Michael G.