Preferential involvement of Na+/Ca2+ exchanger type-1 in the brain damage caused by transient focal cerebral ischemia in mice

Nobutaka Morimoto, Satomi Kita, Masamitsu Shimazawa, Hiroko Namimatsu, Kazuhiro Tsuruma, Kazuhide Hayakawa, Kenichi Mishima, Nobuaki Egashira, Takuya Iyoda, Ichiro Horie, Yusuke Gotoh, Katsunori Iwasaki, Michihiro Fujiwara, Toshio Matsuda, Akemichi Baba, Issei Komuro, Kyoji Horie, Junji Takeda, Takahiro Iwamoto, Hideaki Hara

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)


The Na+/Ca2+ exchanger (NCX), an ion-transporter located in the plasma membrane of neuronal cells, contributes to intracellular Ca2+ homeostasis. Within the brain, three isoforms (NCX1, NCX2, and NCX3) are widely distributed. However, it is not clear to what extent these isoforms are involved in ischemic brain damage in mammals. We therefore used genetically altered mice and isoform-selective NCX inhibitors in a model of transient focal ischemia to investigate the role of each NCX isoform in ischemic brain damage. NCX isoform-mutant mice (NCX1+/-, NCX2+/-, and NCX3+/-) and wild-type mice were subjected to 90min of middle cerebral artery occlusion (MCAO) followed by 24h of reperfusion. One of three NCX inhibitors [SN-6, KB-R7943, or SEA0400 (3 or 10mgkg-1, i.p.)] was administered to ddY mice at 30min before more prolonged (4-h) MCAO followed by 24h of reperfusion. After transient MCAO reperfusion, the cerebral infarcts in NCX1+/- mice, but not those in NCX2+/- or NCX3+/- mice, were significantly smaller than those in wild-type mice. SN-6 and SEA0400, which are more selective for the NCX1 isoform, significantly reduced the infarct volume at 10mg/kg. In contrast, KB-R7943, which is more selective for NCX3, did not. These results suggest that the NCX1 isoform may act preferentially (vs. the NCX2 and NCX3 isoforms) to exacerbate the cerebral damage caused by ischemic insult in mice, and that NCX1-selective inhibitors warrant investigation as a potential therapeutic agents for stroke.

Original languageEnglish
Pages (from-to)186-190
Number of pages5
JournalBiochemical and Biophysical Research Communications
Issue number3-4
Publication statusPublished - Dec 14 2012

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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