Perinatal chronic hypoxia induces cortical inflammation, hypomyelination, and peripheral myelin-specific t cell autoreactivity

Sterling B. Ortega, Xiagmei Kong, Ramgopal Venkataraman, Allen Michael Savedra, Steven G. Kernie, Ann M. Stowe, Lakshmi Raman

Research output: Contribution to journalArticle

10 Scopus citations

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, myelinproducing 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.

Original languageEnglish (US)
Pages (from-to)21-29
Number of pages9
JournalJournal of Leukocyte Biology
Volume99
Issue number1
DOIs
StatePublished - Jan 1 2016

Keywords

  • CD4 T cells
  • Motor function
  • Myelination
  • Oligodendrocyte progenitors
  • Periventricular leukomalacia

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

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