Riluzole improves functional recovery after acute spinal cord injury in rats and may be associated with changes in spinal microglia/macrophages polarization

Riluzole improves functional recovery after acute spinal cord injury in rats and may be associated with changes in spinal microglia/macrophages polarization
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利鲁唑可改善大鼠急性脊髓损伤后的功能恢复,并可能与脊髓小胶质细胞/巨噬细胞极化的变化有关

DOI:
10.1016/j.neulet.2020.134829
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发表时间:
2020-02
影响因子:
2.5
通讯作者:
Xueming Chen
Xueming Chen
中科院分区:
医学4区
文献类型:
--
作者:
Qichao Wu;Yan Zhang;Yanjun Zhang;Wenkai Zhang;Wenxiu Zhang;Yadong Liu;Songjie Xu;Yun Guan;Xueming Chen

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脊髓损伤(SCI)引发明显的炎症反应,并伴有神经元破坏和功能缺陷。脊髓损伤治疗仍然是一个未满足的临床需求。新出现的证据表明,利鲁唑可能由于其抗炎特性而发挥神经保护作用。然而,其潜在机制的细节仍不明确。小胶质/巨噬细胞的极化在神经炎症中起重要作用。在这里,我们研究了利鲁唑是否可以在急性脊髓损伤后发挥神经保护作用,以及这种作用是否与小胶质细胞/巨噬细胞极化的变化有关。雌性大鼠脊髓损伤后立即腹腔注射利鲁唑(4 mg/kg)或对照物,连续7天(b.i.d)。与载药组比较,利鲁唑治疗的脊髓损伤大鼠运动评分显著提高(Basso, Beattie, and Bresnahan评分,斜面测试评分,n = 18/组)。在脊髓损伤后7天,利鲁唑治疗的大鼠脊髓腔变小,髓鞘碱性蛋白(MBP)和神经丝(NF)200免疫反应水平升高,脊髓促炎细胞因子水平降低。免疫荧光研究显示,与对照相比,利鲁唑治疗的脊髓损伤大鼠脊髓中CD206+细胞增多,iNOS+细胞减少。通过实时PCR,我们发现与对照剂处理相比,利鲁唑上调了M2标记的mRNA水平,但下调了M1标记的mRNA水平。目前的研究结果表明,急性脊髓损伤后全身给予利鲁唑可促进运动功能恢复并抑制炎症反应,这可能与M2小胶质细胞/巨噬细胞的极化有关。
Spinal cord injury (SCI) triggers pronounced inflammatory responses that are accompanied by neuronal disruption and functional deficits. SCI treatment remains an unmet clinical need. Emerging evidence suggests that riluzole may exert a neuroprotective effect due to its anti-inflammatory properties. However, details of the underlying mechanisms remain poorly defined. The polarization of microglial/macrophages has an important role in neuroinflammation. Here, we examined whether riluzole can exert a neuroprotective effect after acute SCI, and whether this effect is associated with changes in microglia/macrophages polarization. Riluzole (4 mg/kg) or vehicle were injected intraperitoneally (i.p.) in female rats immediately following SCI and repeated for 7 consecutive days (b.i.d.). Compared with vehicle treatment, riluzole-treated SCI rats showed significant higher locomotor scores (Basso, Beattie, and Bresnahan score, Inclined Plane test score, n = 18/group). Riluzole-treated rats also developed smaller spinal cavities, showed higher levels of myelin basic protein (MBP) and neurofilament (NF)200 immunoreactivities, and lower levels of proinflammatory cytokines in the spinal cord at 7 days post-SCI. Immunofluorescence study revealed more CD206+cells and less iNOS+cells in the injured spinal cord of riluzole-treated SCI rats, as compared to vehicle control. Using real-time PCR, we found that riluzole upregulated the mRNA levels of M2 markers, but downregulated that of M1 markers, as compared to the vehicle treatment. Current findings suggest that systemic administration of riluzole after acute SCI facilitated motor function recovery and inhibited inflammatory responses, which may be associated with polarization of M2 microglia/macrophages.
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