Lymphocytes Contribute to the Pathophysiology of Neonatal Brain Injury
BackgroundPeriventricular leukomalacia (PVL) is the most common form of preterm brain injury affecting the cerebral white matter. This type of injury involves a multiphase process and is induced by many factors, including hypoxia–ischemia (HI) and infection. Previous studies have suggested that lymp...
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| Format: | Article |
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Frontiers Media S.A.
2018-03-01
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| Series: | Frontiers in Neurology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fneur.2018.00159/full |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Arshed Nazmi Anna-Maj Albertsson Eridan Rocha-Ferreira Xiaoli Zhang Xiaoli Zhang Xiaoli Zhang Regina Vontell Aura Zelco Mary Rutherford Changlian Zhu Changlian Zhu Changlian Zhu Gisela Nilsson Carina Mallard Henrik Hagberg Henrik Hagberg Henrik Hagberg Jacqueline C. Y. Lai Jianmei W. Leavenworth Jianmei W. Leavenworth Xiaoyang Wang Xiaoyang Wang |
| spellingShingle |
Arshed Nazmi Anna-Maj Albertsson Eridan Rocha-Ferreira Xiaoli Zhang Xiaoli Zhang Xiaoli Zhang Regina Vontell Aura Zelco Mary Rutherford Changlian Zhu Changlian Zhu Changlian Zhu Gisela Nilsson Carina Mallard Henrik Hagberg Henrik Hagberg Henrik Hagberg Jacqueline C. Y. Lai Jianmei W. Leavenworth Jianmei W. Leavenworth Xiaoyang Wang Xiaoyang Wang Lymphocytes Contribute to the Pathophysiology of Neonatal Brain Injury Frontiers in Neurology lymphocytes preterm brain damage mouse models hypoxia–ischemia brain |
| author_facet |
Arshed Nazmi Anna-Maj Albertsson Eridan Rocha-Ferreira Xiaoli Zhang Xiaoli Zhang Xiaoli Zhang Regina Vontell Aura Zelco Mary Rutherford Changlian Zhu Changlian Zhu Changlian Zhu Gisela Nilsson Carina Mallard Henrik Hagberg Henrik Hagberg Henrik Hagberg Jacqueline C. Y. Lai Jianmei W. Leavenworth Jianmei W. Leavenworth Xiaoyang Wang Xiaoyang Wang |
| author_sort |
Arshed Nazmi |
| title |
Lymphocytes Contribute to the Pathophysiology of Neonatal Brain Injury |
| title_short |
Lymphocytes Contribute to the Pathophysiology of Neonatal Brain Injury |
| title_full |
Lymphocytes Contribute to the Pathophysiology of Neonatal Brain Injury |
| title_fullStr |
Lymphocytes Contribute to the Pathophysiology of Neonatal Brain Injury |
| title_full_unstemmed |
Lymphocytes Contribute to the Pathophysiology of Neonatal Brain Injury |
| title_sort |
lymphocytes contribute to the pathophysiology of neonatal brain injury |
| publisher |
Frontiers Media S.A. |
| series |
Frontiers in Neurology |
| issn |
1664-2295 |
| publishDate |
2018-03-01 |
| description |
BackgroundPeriventricular leukomalacia (PVL) is the most common form of preterm brain injury affecting the cerebral white matter. This type of injury involves a multiphase process and is induced by many factors, including hypoxia–ischemia (HI) and infection. Previous studies have suggested that lymphocytes play a significant role in the pathogenesis of brain injury, and the aim of this study was to determine the contribution of lymphocyte subsets to preterm brain injury.MethodsImmunohistochemistry on brain sections from neonatal mice was performed to evaluate the extent of brain injury in wild-type and T cell and B cell-deficient neonatal mice (Rag1−/− mice) using a mouse model of HI-induced preterm brain injury. Flow cytometry was performed to determine the presence of different types of immune cells in mouse brains following HI. In addition, immunostaining for CD3 T cells and CD20 B cells was performed on postmortem preterm human infant brains with PVL.ResultsMature lymphocyte-deficient Rag1−/− mice showed protection from white matter loss compared to wild type mice as indicated by myelin basic protein immunostaining of mouse brains. CD3+ T cells and CD20+ B cells were observed in the postmortem preterm infant brains with PVL. Flow cytometry analysis of mouse brains after HI-induced injury showed increased frequency of CD3+ T, αβT and B cells at 7 days after HI in the ipsilateral (injured) hemisphere compared to the contralateral (control, uninjured) hemisphere.ConclusionLymphocytes were found in the injured brain after injury in both mice and humans, and lack of mature lymphocytes protected neonatal mice from HI-induced brain white matter injury. This finding provides insight into the pathology of perinatal brain injury and suggests new avenues for the development of therapeutic strategies. |
| topic |
lymphocytes preterm brain damage mouse models hypoxia–ischemia brain |
| url |
http://journal.frontiersin.org/article/10.3389/fneur.2018.00159/full |
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doaj-1acfdcdfafea4d7b84e1098d16cd3f9f2020-11-25T01:06:47ZengFrontiers Media S.A.Frontiers in Neurology1664-22952018-03-01910.3389/fneur.2018.00159330936Lymphocytes Contribute to the Pathophysiology of Neonatal Brain InjuryArshed Nazmi0Anna-Maj Albertsson1Eridan Rocha-Ferreira2Xiaoli Zhang3Xiaoli Zhang4Xiaoli Zhang5Regina Vontell6Aura Zelco7Mary Rutherford8Changlian Zhu9Changlian Zhu10Changlian Zhu11Gisela Nilsson12Carina Mallard13Henrik Hagberg14Henrik Hagberg15Henrik Hagberg16Jacqueline C. Y. Lai17Jianmei W. Leavenworth18Jianmei W. Leavenworth19Xiaoyang Wang20Xiaoyang Wang21Department of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Clinical Sciences, Sahlgrenska University Hospital, Gothenburg, SwedenDepartment of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Pediatrics, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Key Laboratory of Child Brain Injury, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Perinatal Imaging and Health, Centre for the Developing Brain, King’s College London, St. Thomas’ Hospital, London, United KingdomDepartment of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Perinatal Imaging and Health, Centre for the Developing Brain, King’s College London, St. Thomas’ Hospital, London, United KingdomDepartment of Pediatrics, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaHenan Key Laboratory of Child Brain Injury, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Neuroscience and Physiology, Center for Brain Repair and Rehabilitation, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Clinical Sciences, Sahlgrenska University Hospital, Gothenburg, SwedenDepartment of Perinatal Imaging and Health, Centre for the Developing Brain, King’s College London, St. Thomas’ Hospital, London, United KingdomDepartment of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Neurosurgery, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Microbiology, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Pediatrics, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaBackgroundPeriventricular leukomalacia (PVL) is the most common form of preterm brain injury affecting the cerebral white matter. This type of injury involves a multiphase process and is induced by many factors, including hypoxia–ischemia (HI) and infection. Previous studies have suggested that lymphocytes play a significant role in the pathogenesis of brain injury, and the aim of this study was to determine the contribution of lymphocyte subsets to preterm brain injury.MethodsImmunohistochemistry on brain sections from neonatal mice was performed to evaluate the extent of brain injury in wild-type and T cell and B cell-deficient neonatal mice (Rag1−/− mice) using a mouse model of HI-induced preterm brain injury. Flow cytometry was performed to determine the presence of different types of immune cells in mouse brains following HI. In addition, immunostaining for CD3 T cells and CD20 B cells was performed on postmortem preterm human infant brains with PVL.ResultsMature lymphocyte-deficient Rag1−/− mice showed protection from white matter loss compared to wild type mice as indicated by myelin basic protein immunostaining of mouse brains. CD3+ T cells and CD20+ B cells were observed in the postmortem preterm infant brains with PVL. Flow cytometry analysis of mouse brains after HI-induced injury showed increased frequency of CD3+ T, αβT and B cells at 7 days after HI in the ipsilateral (injured) hemisphere compared to the contralateral (control, uninjured) hemisphere.ConclusionLymphocytes were found in the injured brain after injury in both mice and humans, and lack of mature lymphocytes protected neonatal mice from HI-induced brain white matter injury. This finding provides insight into the pathology of perinatal brain injury and suggests new avenues for the development of therapeutic strategies.http://journal.frontiersin.org/article/10.3389/fneur.2018.00159/fulllymphocytespretermbrain damagemouse modelshypoxia–ischemiabrain |