Alpha1-antitrypsin protects the immature mouse brain following hypoxic-ischemic injury
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, mi...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-03-01
|
| Series: | Frontiers in Cellular Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2023.1137497/full |
| _version_ | 1811159574932094976 |
|---|---|
| author | Shan Zhang Shan Zhang Wendong Li Yiran Xu Tao Li Tao Li Joakim Ek Xiaoli Zhang Yafeng Wang Yafeng Wang Juan Song Changlian Zhu Changlian Zhu Changlian Zhu Xiaoyang Wang Xiaoyang Wang Xiaoyang Wang |
| author_facet | Shan Zhang Shan Zhang Wendong Li Yiran Xu Tao Li Tao Li Joakim Ek Xiaoli Zhang Yafeng Wang Yafeng Wang Juan Song Changlian Zhu Changlian Zhu Changlian Zhu Xiaoyang Wang Xiaoyang Wang Xiaoyang Wang |
| author_sort | Shan Zhang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T05:44:37Z |
| format | Article |
| id | doaj.art-c19ed1850b9b486bbaed4e22f565a25f |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-04-10T05:44:37Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-c19ed1850b9b486bbaed4e22f565a25f2023-03-06T04:56:07ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022023-03-011710.3389/fncel.2023.11374971137497Alpha1-antitrypsin protects the immature mouse brain following hypoxic-ischemic injuryShan Zhang0Shan Zhang1Wendong Li2Yiran Xu3Tao Li4Tao Li5Joakim Ek6Xiaoli Zhang7Yafeng Wang8Yafeng Wang9Juan Song10Changlian Zhu11Changlian Zhu12Changlian Zhu13Xiaoyang Wang14Xiaoyang Wang15Xiaoyang Wang16Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaCenter for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, SwedenHenan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaCenter for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, SwedenHenan Children’s Neurodevelopment Engineering Research Center, Children’s Hospital Affiliated to Zhengzhou University, Zhengzhou, ChinaCentre of Perinatal Medicine and Health, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, SwedenHenan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaCenter for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, SwedenHenan Children’s Neurodevelopment Engineering Research Center, Children’s Hospital Affiliated to Zhengzhou University, Zhengzhou, ChinaHenan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaCenter for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, SwedenDepartment of Women’s and Children’s Health, Karolinska Institutet, Stockholm, SwedenHenan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaCentre of Perinatal Medicine and Health, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, SwedenCentre of Perinatal Medicine and Health, Institute of Clinical Science, University of Gothenburg, Gothenburg, SwedenIntroduction: 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.https://www.frontiersin.org/articles/10.3389/fncel.2023.1137497/fullalpha1-antitrypsinneuroprotectionhypoxia-ischemianeonatal brain injuryimmature brainmotor dysfunction |
| spellingShingle | Shan Zhang Shan Zhang Wendong Li Yiran Xu Tao Li Tao Li Joakim Ek Xiaoli Zhang Yafeng Wang Yafeng Wang Juan Song Changlian Zhu Changlian Zhu Changlian Zhu Xiaoyang Wang Xiaoyang Wang Xiaoyang Wang Alpha1-antitrypsin protects the immature mouse brain following hypoxic-ischemic injury Frontiers in Cellular Neuroscience alpha1-antitrypsin neuroprotection hypoxia-ischemia neonatal brain injury immature brain motor dysfunction |
| title | Alpha1-antitrypsin protects the immature mouse brain following hypoxic-ischemic injury |
| title_full | Alpha1-antitrypsin protects the immature mouse brain following hypoxic-ischemic injury |
| title_fullStr | Alpha1-antitrypsin protects the immature mouse brain following hypoxic-ischemic injury |
| title_full_unstemmed | Alpha1-antitrypsin protects the immature mouse brain following hypoxic-ischemic injury |
| title_short | Alpha1-antitrypsin protects the immature mouse brain following hypoxic-ischemic injury |
| title_sort | alpha1 antitrypsin protects the immature mouse brain following hypoxic ischemic injury |
| topic | alpha1-antitrypsin neuroprotection hypoxia-ischemia neonatal brain injury immature brain motor dysfunction |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2023.1137497/full |
| work_keys_str_mv | AT shanzhang alpha1antitrypsinprotectstheimmaturemousebrainfollowinghypoxicischemicinjury AT shanzhang alpha1antitrypsinprotectstheimmaturemousebrainfollowinghypoxicischemicinjury AT wendongli alpha1antitrypsinprotectstheimmaturemousebrainfollowinghypoxicischemicinjury AT yiranxu alpha1antitrypsinprotectstheimmaturemousebrainfollowinghypoxicischemicinjury AT taoli alpha1antitrypsinprotectstheimmaturemousebrainfollowinghypoxicischemicinjury AT taoli alpha1antitrypsinprotectstheimmaturemousebrainfollowinghypoxicischemicinjury AT joakimek alpha1antitrypsinprotectstheimmaturemousebrainfollowinghypoxicischemicinjury AT xiaolizhang alpha1antitrypsinprotectstheimmaturemousebrainfollowinghypoxicischemicinjury AT yafengwang alpha1antitrypsinprotectstheimmaturemousebrainfollowinghypoxicischemicinjury AT yafengwang alpha1antitrypsinprotectstheimmaturemousebrainfollowinghypoxicischemicinjury AT juansong alpha1antitrypsinprotectstheimmaturemousebrainfollowinghypoxicischemicinjury AT changlianzhu alpha1antitrypsinprotectstheimmaturemousebrainfollowinghypoxicischemicinjury AT changlianzhu alpha1antitrypsinprotectstheimmaturemousebrainfollowinghypoxicischemicinjury AT changlianzhu alpha1antitrypsinprotectstheimmaturemousebrainfollowinghypoxicischemicinjury AT xiaoyangwang alpha1antitrypsinprotectstheimmaturemousebrainfollowinghypoxicischemicinjury AT xiaoyangwang alpha1antitrypsinprotectstheimmaturemousebrainfollowinghypoxicischemicinjury AT xiaoyangwang alpha1antitrypsinprotectstheimmaturemousebrainfollowinghypoxicischemicinjury |