Protective effect of zinc against ischemic neuronal injury in a middle cerebral artery occlusion model

Youji Kitamura, Yasuhiko Iida, Jun Abe, Masashi Ueda, Masaki Mifune, Fumiyo Kasuya, Masayuki Ohta, Kazuo Igarashi, Yutaka Saito, Hideo Saji

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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.

Original languageEnglish
Pages (from-to)142-148
Number of pages7
JournalJournal of Pharmacological Sciences
Volume100
Issue number2
DOIs
Publication statusPublished - 2006

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Keywords

  • CaEDTA
  • Glutamate
  • Ischemia
  • Middle cerebral artery occlusion
  • Zinc

ASJC Scopus subject areas

  • Pharmacology

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