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Inhaled nitric oxide protects males but not females from neonatal mouse hypoxia-ischemia brain injury

Journal article
Authors Changlian Zhu
Yanyan Sun
Jianfeng Gao
Xiaoyang Wang
Nikolaus Plesnila
Klas Blomgren
Published in Translational Stroke Research
Volume 4
Issue 2
Pages 201-207
ISSN 1868-4483
Publication year 2013
Published at Institute of Neuroscience and Physiology
Institute of Neuroscience and Physiology, Department of Physiology
Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation
Institute of Clinical Sciences, Department of Pediatrics
Pages 201-207
Language en
Keywords perinatal, asphyxia, brain, gender
Subject categories Pediatrics


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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