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Inhaled Nitric Oxide Protects Males But not Females from Neonatal Mouse Hypoxia–Ischemia Brain Injury

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Abstract

It was recently discovered that while under normal conditions inhaled nitric oxide (iNO) does not affect cerebral blood flow, it selectively dilates arterioles in the ischemic penumbra during experimental cerebral ischemia, thereby increasing collateral blood flow and reducing ischemic brain damage. The mechanism was verified in multiple models, but only in male animals. Our aim was to evaluate the effects of iNO on brain injury in neonatal males and females. Nine-day-old mice were subjected to unilateral hypoxia–ischemia (HI), using 10 % oxygen balanced with nitrogen, with or without 50 ppm NO. Brain injury 72 h after HI was reduced by iNO as judged by percentage of injury (−21.7 %), atrophy (−23.7 %), and total pathological score (−29 %). The injury was significantly reduced in males (−32.4 %, p < 0.05) but not in females (−7.1 %, n.s.). Neither the numbers nor the proliferation rates of neural stem cells in the dentate gyrus were affected by iNO. In summary, intraischemic iNO reduced neonatal HI brain injury in a gender-related manner.

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Acknowledgments

This work was supported by the Swedish Research Council, the Swedish Childhood Cancer Foundation (Barncancerfonden), governmental grants from Agreement concerning research and education of doctors (ALF), the Swedish Medical Society (SLS), the Sten A. Olsson’s Foundation, the National Natural Science Foundation of China (to CZ; 31271152), the Wilhelm and Martina Lundgren Foundation, the Frimurare Barnhus Foundation, the Third Phase 211 project of Zhengzhou University, the Health Department of Henan Province, Edit Jacobson’s Donation Foundation, Kungl. Vetenskaps- och Vitterhetssamhället i Göteborg, the Gothenburg Medical Society, the Swedish Medical Society, Aina Wallström’s and Mary-Ann Sjöblom’s Foundation, the Ulla and Rune Amlöv Foundation, AFA Insurance, and the Swedish Society of Medicine.

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Authors and Affiliations

  1. Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Box 432, SE 405 30, Göteborg, Sweden

    Changlian Zhu, Yanyan Sun, Jianfeng Gao & Klas Blomgren

  2. Department of Pediatrics, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China

    Changlian Zhu, Yanyan Sun & Xiaoyang Wang

  3. Department of Pediatrics, Zhengzhou Children’s Hospital, Zhengzhou, China

    Yanyan Sun

  4. Department of Physiology, Henan Chinese Medical College, Zhengzhou, China

    Jianfeng Gao

  5. Perinatal Center, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

    Xiaoyang Wang

  6. Institute for Stroke and Dementia Research, University of Munich Medical School, Munich, Germany

    Nikolaus Plesnila

  7. Department of Pediatrics, Queen Silvia Children’s Hospital, University of Gothenburg, SE 416 85, Gothenburg, Sweden

    Klas Blomgren

  8. Department of Women’s and Children’s Health, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden

    Klas Blomgren

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  1. Changlian Zhu
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Correspondence to Changlian Zhu.

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Zhu, C., Sun, Y., Gao, J. et al. Inhaled Nitric Oxide Protects Males But not Females from Neonatal Mouse Hypoxia–Ischemia Brain Injury. Transl. Stroke Res. 4, 201–207 (2013). https://doi.org/10.1007/s12975-012-0217-2

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  • DOI: https://doi.org/10.1007/s12975-012-0217-2

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