Perinatal chronic hypoxia induces cortical inflammation, hypomyelination, and peripheral myelin‐specific T cell autoreactivity. Issue 1 (2nd June 2015)

• Record Type: Journal Article
• Authors: Ortega, Sterling B.; Kong, Xiagmei; Venkataraman, Ramgopal; Savedra, Allen Michael; Kernie, Steven G.; Stowe, Ann M.; Raman, Lakshmi
• Is Part Of: Journal of leukocyte biology. Volume 99:Issue 1(2016)
• Page Start: 21
• Page End: 29
• Publication Date: 2015-06-02
• Subjects: oligodendrocyte progenitors -- myelination -- CD4 T cells -- periventricular leukomalacia -- motor function; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.5HI0914-447R
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract : Chronic hypoxia leads to a loss of myelin in the developing perinatal brain, and an adaptive immune response to myelin in the periphery. Abstract : pCH is an important risk factor for brain injury and long‐term morbidity in children, occurring during the developmental stages of neurogenesis, neuronal migration, and myelination. We show that a rodent model of pCH results in an early decrease in mature myelin. Although pCH does increase progenitor oligodendrocytes in the developing brain, BrdU labeling revealed a loss in dividing progenitor oligodendrocytes, indicating a defect in mature cell replacement and myelinogenesis. Mice continued to exhibited hypomyelination, concomitant with long‐term impairment of motor function, weeks after cessation of pCH. The implication of a novel neuroimmunologic interplay, pCH also induced a significant egress of infiltrating CD4 T cells into the developing brain. This pCH‐mediated neuroinflammation included oligodendrocyte‐directed autoimmunity, with an increase in peripheral myelin‐specific CD4 T cells. Thus, both the loss of available, mature, myelin‐producing glial cells and an active increase in autoreactive, myelin‐specific CD4 T cell infiltration into pCH brains may contribute to early pCH‐induced hypomyelination in the developing CNS. The elucidation of potential mechanisms of hypoxia‐driven autoimmunity will expand our understanding of the neuroimmune axis during perinatal CNS disease states that may contribute to long‐term functional disability.