Microglial inhibitory factor (MIF/TKP) mitigates secondary damage following spinal cord injury.
Microglial inhibitory factor (MIF/TKP) mitigates secondary damage following spinal cord injury.
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DOI：
10.1016/j.nbd.2012.05.001
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发表时间：
2012-09
影响因子：
6.1
通讯作者：
Tsirka, Stella E.
中科院分区：
文献类型：
--
作者：
Emmetsberger, Jaime;Tsirka, Stella E.
脊髓损伤(SCI)诱导一种免疫反应，在此过程中，中枢神经系统的常驻免疫活性细胞小胶质细胞被激活并迁移到损伤部位。根据激活状态的不同，小胶质细胞会分泌神经毒性或神经营养因子，影响周围环境，并在脊髓损伤后产生有害或修复作用，包括造成或保护旁观者对附近未受损组织的损害。随后巨噬细胞的渗透参与了脊髓损伤的转归。在小鼠脊髓背侧半横断模型中，用三肽巨噬细胞/小胶质细胞抑制因子(MIF/TKP)抑制小胶质细胞/巨噬细胞的激活可以减少损伤中心周围的继发性损伤，减少星形胶质细胞的肥大改变，并导致损伤中心内轴突数量的增加。此外，及时抑制小胶质/巨噬细胞的激活，通过调节少突胶质细胞的存活和少突胶质细胞前体的成熟，防止了脱髓鞘和轴突死亡。位于病变内部或邻近的小胶质细胞/巨噬细胞产生神经毒性因子，如肿瘤坏死因子-α(肿瘤坏死因子-α)。这些结果表明，损伤后早期震中的小胶质细胞/巨噬细胞具有神经毒性，有助于脱髓鞘和轴突变性，MIF/TKP可以与其他治疗方法联合使用，以促进功能恢复。
Spinal cord injury (SCI) induces an immune response during which microglia, the resident immunocompetent cells of the central nervous system, become activated and migrate to the site of damage. Depending on their state of activation, microglia secrete neurotoxic or neurotrophic factors that influence the surrounding environment and have a detrimental or restorative effect following SCI, including causing or protecting bystander damage to nearby undamaged tissue. Subsequent infiltration of macrophages contributes to the SCI outcome. We show here that suppressing microglia/macrophage activation using the tripeptide macrophage/microglia inhibitory factor (MIF/TKP) reduced secondary injury around the lesion epicenter in the murine dorsal hemisection model of SCI; it decreased the hypertrophic change of astrocytes and caused an increase in the number of axons present within the lesion epicenter. Moreover, timely inhibition of microglial/macrophage activation prevented demyelination and axonal dieback by modulating oligodendrocyte survival and oligodendrocyte precursor maturation. Microglia/macrophages located within or proximal to the lesion produced neurotoxic factors, such as tumor necrosis factor alpha (TNF-α). These results suggest that microglia/macrophages within the epicenter at early time points post injury are neurotoxic, contributing to demyelination and axonal degeneration and that MIF/TKP could be used in combination with other therapies to promote functional recovery.
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