Protective effect of zinc against ischemic neuronal injury in a middle cerebral artery occlusion model.
In this study, we investigated the effect of vesicular zinc on ischemic neuronal injury. In cultured neurons, addition of a low concentration (under 100 microM) of zinc inhibited both glutamate-induced calcium influx and neuronal death. In contrast, a higher concentration (over 150 microM) of zinc decreased neuronal viability, although calcium influx was inhibited. These results indicate that zinc exhibits biphasic effects depending on its concentration. Furthermore, in cultured neurons, co-addition of glutamate and CaEDTA, which binds extra-cellular zinc, increased glutamate-induced calcium influx and aggravated the neurotoxicity of glutamate. In a rat transient middle cerebral artery occlusion (MCAO) model, the infarction volume, which is related to the neurotoxicity of glutamate, increased rapidly on the intracerebral ventricular injection of CaEDTA 30 min prior to occlusion. These results suggest that zinc released from synaptic vesicles may provide a protective effect against ischemic neuronal injury.
Graduate School of Medicine and Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
Youji
Y
Kitamura
Yasuhiko
Y
Iida
Jun
J
Abe
Masashi
M
Ueda
Masaki
M
Mifune
Fumiyo
F
Kasuya
Masayuki
M
Ohta
Kazuo
K
Igarashi
Yutaka
Y
Saito
Hideo
H
Saji
D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D002132:Calcium Radioisotopes / Q000378:metabolism; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005029:Ethylenediamines / Q000494:pharmacology; D018698:Glutamic Acid / Q000633:toxicity; D006624:Hippocampus / Q000166:cytology; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007276:Injections, Intraventricular; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020011:Protective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D015032:Zinc / Q000008:administration & dosage / Q000494:pharmacology*
D002132:Calcium Radioisotopes; D002614:Chelating Agents; D005029:Ethylenediamines; D020011:Protective Agents; D018698:Glutamic Acid; D015032:Zinc; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine; D002118:Calcium