Protective Effect of Zinc Against Ischemic Neuronal Injury in a Middle Cerebral Artery Occlusion Model

• Kitamura Youji

  Graduate School of Medicine and Dentistry and Pharmaceutical Sciences, Okayama University, Japan

• Iida Yasuhiko

  Department of Bioimaging, Medical Sciences, Gunma University, Japan

• Abe Jun

  Department of Patho-functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan

• Ueda Masashi

  Department of Patho-functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan

• Mifune Masaki

  Graduate School of Medicine and Dentistry and Pharmaceutical Sciences, Okayama University, Japan

• Kasuya Fumiyo

  Department of Toxicology, Pharmaceutical Sciences, Kobegakuin University, Japan

• Ohta Masayuki

  Department of Toxicology, Pharmaceutical Sciences, Kobegakuin University, Japan

• Igarashi Kazuo

  Department of Chemistry, Virginia Polytechnic Institute and State University, USA

• Saito Yutaka

  Graduate School of Medicine and Dentistry and Pharmaceutical Sciences, Okayama University, Japan

• Saji Hideo

  Department of Patho-functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan

Abstract

In this study, we investigated the effect of vesicular zinc on ischemic neuronal injury. In cultured neurons, addition of a low concentration (under 100 μM) of zinc inhibited both glutamate-induced calcium influx and neuronal death. In contrast, a higher concentration (over 150 μM) 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.<br>

Journal

• Journal of Pharmacological Sciences

  Journal of Pharmacological Sciences 100 (2), 142-148, 2006

  The Japanese Pharmacological Society

Keywords

• zinc
• ischemia
• glutamate
• middle cerebral artery occlusion
• CaEDTA

Details

• CRID: 1390282680154284544
• NII Article ID: 10018240763
• NII Book ID: AA11806667
• DOI: 10.1254/jphs.fp0050805
• ISSN: 13478648
• ISSN: 13478613
• NDL BIB ID: 7821858
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I7821858
• Web Site: https://search.jamas.or.jp/link/ui/2006310784
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
• Abstract License Flag: Disallowed