title: Clioquinol inhibits zinc-triggered caspase activation in the hippocampal CA1 region of a global ischemic gerbil model.
abstract: BACKGROUND
  Excessive release of chelatable zinc from excitatory synaptic vesicles is involved in the pathogenesis of selective neuronal cell death following transient forebrain ischemia. The present study was designed to examine the neuroprotective effect of a membrane-permeable zinc chelator, clioquinol (CQ), in the CA1 region of the gerbil hippocampus after transient global ischemia.
  
  
  RESULTS
  The common carotid arteries were occluded bilaterally, and CQ (10 mg/kg, i.p.) was injected into gerbils once a day. The zinc chelating effect of CQ was examined with TSQ fluorescence and autometallography. Neuronal death, the expression levels of caspases and apoptosis inducing factor (AIF) were evaluated using TUNEL, in situ hybridization and Western blotting, respectively. We were able to show for the first time that CQ treatment attenuates the ischemia-induced zinc accumulation in the CA1 pyramidal neurons, accompanied by less neuronal loss in the CA1 field of the hippocampus after ischemia. Furthermore, the expression levels of caspase-3, -9, and AIF were significantly decreased in the hippocampus of CQ-treated gerbils.
  
  
  CONCLUSIONS
  The present study indicates that the neuroprotective effect of CQ is related to downregulation of zinc-triggered caspase activation in the hippocampal CA1 region of gerbils with global ischemia.
authors.affiliation: Key Laboratory of Medical Cell Biology of Ministry of Education of China, College of Basic Medical Sciences, China Medical University, Shenyang, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.forename: He
authors.initials: H
authors.lastname: Xu
authors.forename: Jia-Min
authors.initials: JM
authors.lastname: Zhou
authors.forename: Zhan-You
authors.initials: ZY
authors.lastname: Wang
mesh_terms: D000818:Animals; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D015153:Blotting, Western; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000201:enzymology*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D007464:Clioquinol / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005849:Gerbillinae; D017403:In Situ Hybridization; D008297:Male
chemical_list: D051033:Apoptosis Inducing Factor; D002614:Chelating Agents; D007464:Clioquinol; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases