4,4'-Diisothiocyanostilbene-2,2'-disulfonic Acid (DIDS) Ameliorates Ischemia-Hypoxia-Induced White Matter Damage in Neonatal Rats through Inhibition of the Voltage-Gated Chloride Channel ClC-2.
4,4'-Diisothiocyanostilbene-2,2'-disulfonic Acid (DIDS) Ameliorates Ischemia-Hypoxia-Induced White Matter Damage in Neonatal Rats through Inhibition of the Voltage-Gated Chloride Channel ClC-2.
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DOI：
10.3390/ijms160510457
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发表时间：
2015-05-07
影响因子：
5.6
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Zhao B;Quan H;Ma T;Tian Y;Cai Q;Li H
慢性脑灌注不足被认为会引起白色物质病变（WML），导致认知障碍。以往的研究表明少突胶质细胞（oligodendrocytes，OLs）的炎症和凋亡参与了WMLs的发病机制，但尚未研究出有效的治疗方法。本研究采用慢性脑缺血缺氧大鼠模型，在不同时间点注射氯离子通道阻断剂4，4 '-二异硫氰基芪-2，2'-二磺酸（DIDS）。结果表明，DIDS能显著降低缺血缺氧诱导的新生大鼠脑组织氯通道2（ClC-2）mRNA和蛋白表达水平的升高。同时，DIDS可显著降低缺氧缺血性损伤新生大鼠的活性氧（ROS）浓度，降低诱导型一氧化氮合酶（iNOS）和肿瘤坏死因子-α（TNF-α）mRNA水平。新生大鼠缺氧缺血性脑损伤后胼胝体和其他白色物质的髓鞘染色较正常对照组弱，DIDS可改善这一现象。DIDS还能抑制缺血缺氧后caspase-3和神经胶质细胞抗原2（NG-2）双标阳性细胞数量的增加。损伤后立即给予DIDS可更有效地减轻白色物质对OL的损伤。总之，我们的研究表明，缺血缺氧损伤后早期应用DIDS可能部分保护发育中的OL。
Chronic cerebral hypoperfusion is believed to cause white matter lesions (WMLs), leading to cognitive impairment. Previous studies have shown that inflammation and apoptosis of oligodendrocytes (OLs) are involved in the pathogenesis of WMLs, but effective treatments have not been studied. In this study, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), a chloride (Cl−) channel blocker, was injected into chronic cerebral ischemia-hypoxia rat models at different time points. Our results showed that DIDS significantly reduced the elevated mRNA levels and protein expression of chloride channel 2 (ClC-2) in neonatal rats induced by ischemia-hypoxia. Meanwhile, DIDS application significantly decreased the concentrations of reactive oxygen species (ROS); and the mRNA levels of inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha TNF-α in neonatal rats with hypoxic-ischemic damage. Myelin staining was weaker in neonatal rats with hypoxic-ischemic damage compared to normal controls in corpus callosum and other white matter, which was ameliorated by DIDS. Furthermore, the elevated number of caspase-3 and neural/glial antigen 2 (NG-2) double-labeled positive cells was attenuated by DIDS after ischemia anoxic injury. Administration of DIDS soon after injury alleviated damage to OLs much more effectively in white matter. In conclusion, our study suggests that early application of DIDS after ischemia-hypoxia injury may partially protect developing OLs.
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影响因子：
3.7
作者：
Pamenter ME;Ryu J;Hua ST;Perkins GA;Mendiola VL;Gu XQ;Ellisman MH;Haddad GG
通讯作者：
Haddad GG
影响因子：
--
作者：
Liu, An-Heng;Cao, Ya-Nan;Wang, Xiao-Ming
通讯作者：
Wang, Xiao-Ming
影响因子：
4.2
作者：
Shen, SM;Yu, S;Sun, GY
通讯作者：
Sun, GY
影响因子：
2.9
作者：
Uehara, H;Yoshioka, H;Sawada, T
通讯作者：
Sawada, T
DOI：
10.1085/jgp.201210927
发表时间：
2013-04
期刊：
The Journal of general physiology
影响因子：
--
作者：
Garcia-Celma J;Szydelko A;Dutzler R
通讯作者：
Dutzler R