title: Neuroprotective effect of zinc chelator DEDTC in a zebrafish (Danio rerio) Model of Hypoxic Brain Injury.
abstract: A study was conducted using zebrafish as a model of hypoxic brain injury to investigate the potential neuroprotective effects of zinc (Zn(2+)) chelation. The accumulation of intracellular Zn(2+) is a significant causal factor of the neuronal injury, and has been implicated in cell death followed by ischemic stroke. In this study, the zebrafish was placed in the hypoxia chamber with an extremely low level of dissolved oxygen (less than 0.8 mg/L), which is similar to the conditions in a complete global ischemic stroke. Approximately 50% of zebrafish died after a short period (≈11 min) of hypoxic treatment, suggesting that this is a responsive model system for use in evaluating treatments for hypoxic brain damage. The application of DEDTC reduced intracellular Zn(2+) accumulation and produced a concentration-dependent effect by increasing the survival rate of zebrafish. Zn(2+) chelation also enhanced zebrafish tolerance for hypoxia. When the brain damages were evaluated with TTC staining, the zebrafish that were treated with DEDTC in hypoxic treatment yielded the improvement of TTC staining that was similar to the healthy zebrafish brain. The results support that rising intracellular Zn(2+) plays a critical role in the neuronal damages, and demonstrate the protective effects of Zn(2+) chelation in hypoxic-ischemic brain injury in zebrafish.
authors: Program in Biological Sciences, Ohio University, Athens, OH 45701, USA.
authors: Xinge
authors: X
authors: Yu
authors: Yang V
authors: YV
authors: Li
mesh_terms: D000818:Animals; D002614:Chelating Agents / Q000378:metabolism*; D004195:Disease Models, Animal; D004050:Ditiocarb / Q000031:analogs & derivatives* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D013053:Spectrophotometry; D013778:Tetrazolium Salts / Q000378:metabolism; D015027:Zebrafish; D015032:Zinc / Q000378:metabolism*
chemical_list: D002614:Chelating Agents; D018696:Neuroprotective Agents; D013778:Tetrazolium Salts; C009591:triphenyltetrazolium; D004050:Ditiocarb; C039353:dihydroxyethyldithiocarbamate; D015032:Zinc; D010100:Oxygen