title: Perinatal chronic hypoxia induces cortical inflammation, hypomyelination, and peripheral myelin-specific T cell autoreactivity.
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.
authors.affiliation: Departments of *Neurology and Neurotherapeutics and Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA; Departments of Pediatrics and Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA; and Department of Accounting, School of Business, University of Texas at Arlington, Arlington, Texas, USA.
authors.forename: Sterling B
authors.initials: SB
authors.lastname: Ortega
authors.affiliation: Departments of *Neurology and Neurotherapeutics and Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA; Departments of Pediatrics and Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA; and Department of Accounting, School of Business, University of Texas at Arlington, Arlington, Texas, USA.
authors.forename: Xiagmei
authors.initials: X
authors.lastname: Kong
authors.affiliation: Departments of *Neurology and Neurotherapeutics and Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA; Departments of Pediatrics and Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA; and Department of Accounting, School of Business, University of Texas at Arlington, Arlington, Texas, USA.
authors.forename: Ramgopal
authors.initials: R
authors.lastname: Venkataraman
authors.affiliation: Departments of *Neurology and Neurotherapeutics and Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA; Departments of Pediatrics and Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA; and Department of Accounting, School of Business, University of Texas at Arlington, Arlington, Texas, USA.
authors.forename: Allen Michael
authors.initials: AM
authors.lastname: Savedra
authors.affiliation: Departments of *Neurology and Neurotherapeutics and Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA; Departments of Pediatrics and Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA; and Department of Accounting, School of Business, University of Texas at Arlington, Arlington, Texas, USA.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Kernie
authors.affiliation: Departments of *Neurology and Neurotherapeutics and Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA; Departments of Pediatrics and Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA; and Department of Accounting, School of Business, University of Texas at Arlington, Arlington, Texas, USA ann.stowe@utsouthwestern.edu.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Stowe
authors.affiliation: Departments of *Neurology and Neurotherapeutics and Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA; Departments of Pediatrics and Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA; and Department of Accounting, School of Business, University of Texas at Arlington, Arlington, Texas, USA.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Raman
mesh_terms: D000818:Animals; D015551:Autoimmunity; D001522:Behavior, Animal; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002540:Cerebral Cortex / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D000860:Hypoxia / Q000276:immunology* / Q000378:metabolism*; D007249:Inflammation; D051379:Mice; D009043:Motor Activity; D004676:Myelin Basic Protein / Q000276:immunology; D009186:Myelin Sheath / Q000276:immunology*; D009457:Neuroglia / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology
chemical_list: D004676:Myelin Basic Protein
keywords: CD4 T cells; motor function; myelination; oligodendrocyte progenitors; periventricular leukomalacia