Methylprednisolone Induces Neuro-Protective Effects via the Inhibition of A1 Astrocyte Activation in Traumatic Spinal Cord Injury Mouse Models.
Methylprednisolone Induces Neuro-Protective Effects via the Inhibition of A1 Astrocyte Activation in Traumatic Spinal Cord Injury Mouse Models.
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甲基泼尼松龙通过抑制创伤性脊髓损伤小鼠模型中 A1 星形胶质细胞的激活来诱导神经保护作用。
DOI：
10.3389/fnins.2021.628917
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发表时间：
2021
影响因子：
4.3
通讯作者：
Liu JB
中科院分区：
文献类型：
--
作者：
Zou HJ;Guo SW;Zhu L;Xu X;Liu JB
创伤性脊髓损伤(TSCI)会导致炎症、水肿和神经细胞凋亡等病理变化。甲基强的松龙(MP)是一种糖皮质激素，具有多种有益作用，包括减轻炎症和缺血反应，以及抑制脂质过氧化。然而，甲基强的松龙治疗TSCI的疗效和机制尚不清楚。在本研究中，MP显著减弱了H_2O_2对神经细胞的凋亡作用。Western印迹分析显示，细胞凋亡相关蛋白Bax和裂解的caspase-3水平降低，抗细胞凋亡的Bcl2水平升高。体内TUNEL实验进一步证明，MP对TSCI后神经细胞的凋亡具有保护作用，并与体外研究结果一致。此外，我们还证明MP可以降低脊髓损伤模型小鼠脑内IbA1、Il-1α、肿瘤坏死因子α和C3的表达水平，并抑制A1型神经毒性反应性星形胶质细胞的激活。神经功能评定采用Basso小鼠评定量表(BMS)和足印试验。结果表明，甲基强的松龙能显著提高损伤小鼠的神经功能。综上所述，我们的研究表明，MP可以减轻小鼠急性TSCI后星形胶质细胞的死亡，减少小胶质细胞的激活，抑制A1星形胶质细胞的激活，促进功能恢复。
Traumatic spinal cord injury (TSCI) leads to pathological changes such as inflammation, edema, and neuronal apoptosis. Methylprednisolone (MP) is a glucocorticoid that has a variety of beneficial effects, including decreasing inflammation and ischemic reaction, as well as inhibiting lipid peroxidation. However, the efficacy and mechanism of MP in TSCI therapy is yet to be deciphered. In the present study, MP significantly attenuated the apoptotic effects of H2O2 in neuronal cells. Western blot analysis demonstrated that the levels of apoptotic related proteins, Bax and cleaved caspase-3, were reduced while levels of anti-apoptotic Bcl-2 were increased. In vivo TUNEL assays further demonstrated that MP effectively protected neuronal cells from apoptosis after TSCI, and was consistent with in vitro studies. Furthermore, we demonstrated that MP could decrease expression levels of IBA1, Il-1α, TNFα, and C3 and suppress A1 neurotoxic reactive astrocyte activation in TSCI mouse models. Neurological function was evaluated using the Basso Mouse Scale (BMS) and Footprint Test. Results demonstrated that the neurological function of MP-treated injured mice was significantly increased. In conclusion, our study demonstrated that MP could attenuate astrocyte cell death, decrease microglia activation, suppress A1 astrocytes activation, and promote functional recovery after acute TSCI in mouse models.
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影响因子：
2.5
作者：
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通讯作者：
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通讯作者：
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作者：
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