Alpha1-antitrypsin protects the immature mouse brain following hypoxic-ischemic injury

Frontiers in Cellular Neuroscience

Cellular Neuroscience

Tao Li¹  Yafeng Wang¹  Joakim Ek²  Yiran Xu³  Wendong Li³  Xiaoli Zhang³  Juan Song³  Shan Zhang⁴  Changlian Zhu⁵  Xiaoyang Wang⁶ 

[1] Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden;Henan Children’s Neurodevelopment Engineering Research Center, Children’s Hospital Affiliated to Zhengzhou University, Zhengzhou, China;Centre of Perinatal Medicine and Health, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden;Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China;Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China;Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden;Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China;Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden;Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden;Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China;Centre of Perinatal Medicine and Health, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden;Centre of Perinatal Medicine and Health, Institute of Clinical Science, University of Gothenburg, Gothenburg, Sweden;

关键词: alpha1-antitrypsin;    neuroprotection;    hypoxia-ischemia;    neonatal brain injury;    immature brain;    motor dysfunction;   

DOI  :  10.3389/fncel.2023.1137497

 received in 2023-01-04, accepted in 2023-02-13,  发布年份 2023

来源: Frontiers

【 摘 要 】

Introduction: Preterm brain injury often leads to lifelong disabilities affecting both cognitive and motor functions, and effective therapies are limited. Alpha1-antitrypsin (AAT), an endogenous inhibitor of serine proteinases with anti-inflammatory, anti-apoptotic, and cytoprotective properties, might be beneficial in treating preterm brain injury. The aim of this study was to investigate whether AAT has neuroprotective effects in a mouse preterm brain injury model.Methods: Preterm brain injury was induced on postnatal day 5, and mouse pups’ right common carotid arteries were cut between two ligations followed by hypoxia induction. Brain injury was evaluated through immunohistochemistry staining and magnetic resonance imaging. Fluoro-Jade B and immunohistochemistry staining were performed to investigate the neuronal cell death and blood-brain barrier (BBB) permeability. The motor function and anxiety-like behaviors were revealed by CatWalk gait analysis and the open field test.Results: After hypoxia-ischemia (HI) insult, brain injury was alleviated by AAT treatment, and this was accompanied by reduced BBB permeability, reduced neuronal cell death and caspase-3 activation, and inhibition of microglia activation. In addition, AAT administration significantly improved HI-induced motor function deficiencies in mice. The neuroprotective effect of AAT was more pronounced in male mice.Conclusion: AAT treatment is neuroprotective against preterm brain injury in neonatal mice, and the effect is more pronounced in males.

【 授权许可】

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Copyright © 2023 Zhang, Li, Xu, Li, Ek, Zhang, Wang, Song, Zhu and Wang.