Amiloride Promotes Oligodendrocyte Survival and Remyelination after Spinal Cord Injury in Rats.
Amiloride Promotes Oligodendrocyte Survival and Remyelination after Spinal Cord Injury in Rats.
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DOI：
10.3390/jcm7030046
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发表时间：
2018-03-05
影响因子：
3.9
通讯作者：
Watanabe M
中科院分区：
文献类型：
--
作者：
Imai T;Katoh H;Suyama K;Kuroiwa M;Yanagisawa S;Watanabe M
脊髓损伤后，继发性损伤导致胶质细胞凋亡面积扩大。少突胶质前体细胞（OPCs）在SCI后活跃增殖，但其中许多细胞发生凋亡。内质网应激是导致继发性损伤加重的因素之一。在这项研究中，我们测试了阿米洛利治疗对大鼠二次损伤期间OPCs命运的影响。阿米洛利是FDA批准用于治疗高血压的利尿剂，其在大鼠中增强ER应激反应并抑制SCI后胶质细胞的凋亡。使用无限视野（IH）撞击器（200 kdyne）在Sprague-Dawley大鼠中诱导严重挫伤性SCI。SCI后24小时开始，每天腹腔内给予10 mg/kg阿米洛利或磷酸盐缓冲盐水（PBS），持续14天。在SCI后7、14、28和56天，随后对动物实施安乐死，以分析受损的脊髓。我们标记增殖的OPCs，并证明阿米洛利治疗导致更多的OPCs和少突胶质细胞在损伤的脊髓。观察到髓鞘碱性蛋白（MBP）表达水平增加，表明成熟少突胶质细胞数量增加导致髓鞘再生改善，显著改善运动功能恢复。
After spinal cord injury (SCI), secondary injury results in an expanding area of glial cell apoptosis. Oligodendrocyte precursor cells (OPCs) actively proliferate after SCI, but many of these cells undergo apoptosis. One of the factors that exacerbates secondary injury is endoplasmic reticulum (ER) stress. In this study, we tested the effects of amiloride treatment on the fate of OPCs during secondary injury in rats. Amiloride is an FDA-approved diuretic for treating hypertension, which in rats enhances ER stress response and suppresses the apoptosis of glial cells after SCI. A severe contusive SCI was induced in Sprague-Dawley rats using an infinite horizon (IH)-impactor (200 kdyne). Beginning 24 h after SCI, 10 mg/kg of amiloride or phosphate buffered saline (PBS) was intraperitoneally administered daily for a period of 14 days. At 7, 14, 28, and 56 days after SCI, animals were subsequently euthanized in order to analyze the injured spinal cord. We labeled proliferating OPCs and demonstrated that amiloride treatment led to greater numbers of OPCs and oligodendrocytes in the injured spinal cord. Increased myelin basic protein (MBP) expression levels were observed, suggesting that increased numbers of mature oligodendrocytes led to improved remyelination, significantly improving motor function recovery.
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影响因子：
6.2
作者：
Ohri, Sujata Saraswat;Maddie, Melissa A.;Whittemore, Scott R.
通讯作者：
Whittemore, Scott R.
影响因子：
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Amemiya, S;Kamiya, T;Katayama, Y
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Nishiyama, A
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Uyemura, K
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作者：
Tator, CH
通讯作者：
Tator, CH