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Dietary supplementation with sodium nitrite can exert neuroprotective effects on global cerebral ischemia/reperfusion in mice

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Abstract

Background

Nitrite-derived NO protects against middle cerebral artery occlusion in mice. We developed a new mouse model of global cerebral ischemia and reperfusion (GCI/R) involving reversible occlusion of the major vessels from the aortic arch supplying the brain, and investigated neuroprotection with dietary sodium nitrite supplementation against GCI/R injury.

Methods

Mice received drinking water with (nitrite group) or without (control group) sodium nitrite (2 mM) for 5 days and underwent 3-min GCI/R by reversible occlusion of major vessels from the aortic arch (i.e., brachiocephalic, left common carotid, and left subclavian artery). Survival rates and neurological function scores were evaluated for up to 5 days after GCI/R. Histopathological studies were performed to detect neurological degeneration and caspase-3 activation in serial hippocampal sections.

Results

In the control group, 17/30 mice (57 %) survived 5 days after 3-min GCI/R, whereas in the nitrite group 25/30 mice (83 %) survived (p < 0.05). The neurological score at 5 days after GCI in control group was significantly higher than in the nitrite group. Cerebral blood flow (CBF) during GCI was significantly higher in the nitrite group than in the control group, while MABP did not differ significantly between groups. Degenerative changes and caspase-3 activation in hippocampal sections after GCI were observed in the control group but not in the nitrite group. Pretreatment with the NO scavenger c-PTIO abolished the neuroprotective effects of sodium nitrite.

Conclusions

Sodium nitrite supplementation attenuated mortality and neurological impairment after 3-min GCI in mice; an effect likely mediated via vascular mechanisms involving NO.

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Acknowledgments

We thank Masato Tsutsui MD, Ph.D and Mayuko Sakanashi Ph.D for technical assistance for measuring cGMP level.

Financial Disclosure Statement

This work was supported by a Grant-in-aid for scientific research from the Ministry of Education of JAPAN (B) 25293329 to M. K. and Grant-in-aid for challenging exploratory research JAPAN 25670559 to M. K.

Conflict of interest

Takasuke Fukuda, Manabu Kakinohana, Chitoshi Takayama, Masayuki Matsushita, and Kazuhiro Sugahara have no conflicts of interest to disclose.

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Authors and Affiliations

  1. Department of Anesthesiology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa, 903-0215, Japan

    Takasuke Fukuda & Manabu Kakinohana

  2. Department of Molecular Anatomy, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan

    Chitoshi Takayama

  3. Department of Molecular and Cellular Physiology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan

    Masayuki Matsushita

  4. University of the Ryukyus, Nishihara, Okinawa, Japan

    Kazuhiro Sugahara

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  1. Takasuke Fukuda
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  2. Manabu Kakinohana
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Correspondence to Takasuke Fukuda.

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Fukuda, T., Kakinohana, M., Takayama, C. et al. Dietary supplementation with sodium nitrite can exert neuroprotective effects on global cerebral ischemia/reperfusion in mice. J Anesth 29, 609–617 (2015). https://doi.org/10.1007/s00540-014-1968-6

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  • DOI: https://doi.org/10.1007/s00540-014-1968-6

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