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.