title: 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.
abstract: 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.
authors.affiliation: Battalion 4 of Cadet Brigade, Third Military Medical University, Chongqing 400038, China. baixiong070@163.com.
authors.forename: Baixiong
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Battalion 19 of Bioengineering, Third Military Medical University, Chongqing 400038, China. 18523505503@163.com.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Quan
authors.affiliation: Battalion 7 of Cadet Brigade, Third Military Medical University, Chongqing 400038, China. matt0119@163.com.
authors.forename: Teng
authors.initials: T
authors.lastname: Ma
authors.affiliation: Department of Histology and Embryology, Third Military Medical University, 30# Gaotanyan St, Shapingba District, Chongqing 400038, China. tianyp1981@163.com.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Histology and Embryology, Third Military Medical University, 30# Gaotanyan St, Shapingba District, Chongqing 400038, China. fengcai1112@126.com.
authors.forename: Qiyan
authors.initials: Q
authors.lastname: Cai
authors.affiliation: Department of Histology and Embryology, Third Military Medical University, 30# Gaotanyan St, Shapingba District, Chongqing 400038, China. lihongli@tmmu.edu.cn.
authors.forename: Hongli
authors.initials: H
authors.lastname: Li
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000941:Antigens / Q000378:metabolism; D017209:Apoptosis; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D000090007:CLC-2 Chloride Channels; D053148:Caspase 3 / Q000378:metabolism; D018118:Chloride Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D000941:Antigens; D000090007:CLC-2 Chloride Channels; D053148:Caspase 3; D018118:Chloride Channels; D018696:Neuroprotective Agents; D052247:Nitric Oxide Synthase Type II; D011509:Proteoglycans; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D000099216:Chondroitin Sulfate Proteoglycan 4; C000715429:Clcn2 protein, rat