AUTHOR=Nazmi Arshed , Albertsson Anna-Maj , Rocha-Ferreira Eridan , Zhang Xiaoli , Vontell Regina , Zelco Aura , Rutherford Mary , Zhu Changlian , Nilsson Gisela , Mallard Carina , Hagberg Henrik , Lai Jacqueline C. Y. , Leavenworth Jianmei W. , Wang Xiaoyang 

TITLE=Lymphocytes Contribute to the Pathophysiology of Neonatal Brain Injury

JOURNAL=Frontiers in Neurology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2018.00159

DOI=10.3389/fneur.2018.00159

ISSN=1664-2295

ABSTRACT=<sec id="ST1"><title>Background</title><p>Periventricular 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.</p></sec><sec id="ST2"><title>Methods</title><p>Immunohistochemistry 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 (<italic>Rag1</italic><sup>−/−</sup> 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.</p></sec><sec id="ST3"><title>Results</title><p>Mature lymphocyte-deficient <italic>Rag1</italic><sup>−</sup><italic><sup>/</sup></italic><sup>−</sup> mice showed protection from white matter loss compared to wild type mice as indicated by myelin basic protein immunostaining of mouse brains. CD3<sup>+</sup> T cells and CD20<sup>+</sup> 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<sup>+</sup> T, αβT and B cells at 7 days after HI in the ipsilateral (injured) hemisphere compared to the contralateral (control, uninjured) hemisphere.</p></sec><sec id="ST4"><title>Conclusion</title><p>Lymphocytes 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.</p></sec>