Lymphocytes Contribute to the Pathophysiology of Neonatal Brain Injury

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

doi:10.3389/fneur.2018.00159

Frontiers in Neurology (Mar 2018)

Lymphocytes Contribute to the Pathophysiology of Neonatal Brain Injury

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

Affiliations

Arshed Nazmi: Department of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Anna-Maj Albertsson: Department of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Eridan Rocha-Ferreira: Department of Clinical Sciences, Sahlgrenska University Hospital, Gothenburg, Sweden
Xiaoli Zhang: Department of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Xiaoli Zhang: Department of Pediatrics, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Xiaoli Zhang: Henan Key Laboratory of Child Brain Injury, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Regina Vontell: Department of Perinatal Imaging and Health, Centre for the Developing Brain, King’s College London, St. Thomas’ Hospital, London, United Kingdom
Aura Zelco: Department of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Mary Rutherford: Department of Perinatal Imaging and Health, Centre for the Developing Brain, King’s College London, St. Thomas’ Hospital, London, United Kingdom
Changlian Zhu: Department of Pediatrics, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Changlian Zhu: Henan Key Laboratory of Child Brain Injury, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Changlian Zhu: Department of Neuroscience and Physiology, Center for Brain Repair and Rehabilitation, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Gisela Nilsson: Department of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Carina Mallard: Department of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Henrik Hagberg: Department of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Henrik Hagberg: Department of Clinical Sciences, Sahlgrenska University Hospital, Gothenburg, Sweden
Henrik Hagberg: Department of Perinatal Imaging and Health, Centre for the Developing Brain, King’s College London, St. Thomas’ Hospital, London, United Kingdom
Jacqueline C. Y. Lai: Department of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Jianmei W. Leavenworth: Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, AL, United States
Jianmei W. Leavenworth: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, United States
Xiaoyang Wang: Department of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Xiaoyang Wang: Department of Pediatrics, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China

DOI: https://doi.org/10.3389/fneur.2018.00159
Journal volume & issue: Vol. 9

Abstract

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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.

Published in Frontiers in Neurology

ISSN: 1664-2295 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry: Neurology. Diseases of the nervous system
Website: https://www.frontiersin.org/journals/neurology/

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