First Author | Nazmi A | Year | 2018 |
Journal | Front Neurol | Volume | 9 |
Pages | 159 | PubMed ID | 29615958 |
Mgi Jnum | J:311220 | Mgi Id | MGI:6766313 |
Doi | 10.3389/fneur.2018.00159 | Citation | Nazmi A, et al. (2018) Lymphocytes Contribute to the Pathophysiology of Neonatal Brain Injury. Front Neurol 9:159 |
abstractText | Background: 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. Methods: 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 (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. Results: Mature 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, alphabetaT and B cells at 7 days after HI in the ipsilateral (injured) hemisphere compared to the contralateral (control, uninjured) hemisphere. Conclusion: 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. |