Protective effects of catalpol on oligodendrocyte death and myelin breakdown in a rat model of chronic cerebral hypoperfusion
Protective effects of catalpol on oligodendrocyte death and myelin breakdown in a rat model of chronic cerebral hypoperfusion
复制标题
梓醇对慢性脑低灌注大鼠模型少突胶质细胞死亡和髓磷脂破坏的保护作用
DOI：
10.1016/j.neulet.2011.04.013
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发表时间：
2011-06-15
影响因子：
2.5
通讯作者：
Yao, Zhong-Xiang
中科院分区：
文献类型：
--
作者：
Cai, Qi-Yan;Chen, Xing-Shu;Yao, Zhong-Xiang
慢性脑灌注不足被认为会诱发白质病变 (WML)，并导致少突胶质细胞 (OLG) 死亡和髓磷脂分解。尽管细胞凋亡被认为参与了 WML 的病理过程，但仍然缺乏有效的治疗方法。在本研究中，我们研究了梓醇（一种环烯醚萜苷）是否可以作用于大鼠慢性低灌注模型中的少突胶质细胞（OLG）和髓鞘，以及转录因子 cAMP 反应元件结合蛋白（CREB）磷酸化是否参与由此产生的神经保护作用。采用双侧颈总动脉结扎法制备慢性脑低灌注大鼠模型。低灌注后第 30 天，缺血性白质中的 OLG 损失和髓磷脂破坏比假手术对照组更严重和明显。灌注不足后，大鼠的空间记忆也受到更严重的损害。梓醇治疗显着抑制了 OLG 的减少和髓磷脂的分解，并促进了认知衰退的恢复。梓醇处理也显着增加了 Bcl-2 和磷酸化 CREB (p-CREB) 的表达。总之，梓醇可以通过 p-CREB 信号通路导致 Bcl-2 下游上调，预防低灌注引起的 WML 和认知障碍。我们的结果表明，梓醇可能是治疗脑血管 WML 的有效方法。 (C) 2011 Elsevier Ireland Ltd. 保留所有权利。
Chronic cerebral hypoperfusion is thought to induce white matter lesions (WMLs) with oligodendrocyte (OLG) death and myelin breakdown. Although apoptosis is believed to be involved in the pathologic process of WMLs, effective therapies for such remain lacking. In the present study, we investigated whether catalpol, an iridoid glycoside, could act on oligodendrocytes (OLGs) and myelin sheaths in a rat chronic hypoperfusion model, and whether transcription factor cAMP-responsive element binding protein (CREB) phosphorylation is involved in the resulting neuroprotection. A rat model of chronic cerebral hypoperfusion was prepared by bilateral common carotid artery ligation. On the 30th day after hypoperfusion, OLG loss and myelin disruption in the ischemic white matter were more severe and evident than in the sham control. Spatial memory was also more seriously impaired in rats after hypoperfusion. Treatment with catalpol significantly suppressed diminished OLGs and myelin breakdown, and promoted the recovery of cognitive decline. The expression of Bcl-2 and phosphorylated CREB (p-CREB) was also significantly increased by catalpol treatment. In conclusion, catalpol could protect against hypoperfusion-induced WMLs and cognitive impairment through the p-CREB signaling pathway leading to downstream upregulation of Bcl-2. Our results suggest that catalpol may be a useful approach for treating cerebrovascular WMLs. (C) 2011 Elsevier Ireland Ltd. All rights reserved.