Journal article
Perinatal chronic hypoxia induces cortical inflammation, hypomyelination, and peripheral myelin-specific T cell autoreactivity
Journal of leukocyte biology, Vol.99(1), pp.21-29
01/2016
DOI: 10.1189/jlb.5HI0914-447R
PMID: 26038434
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.
Details
- Title: Subtitle
- Perinatal chronic hypoxia induces cortical inflammation, hypomyelination, and peripheral myelin-specific T cell autoreactivity
- Creators
- Sterling B Ortega - 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, USAXiagmei Kong - 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, USARamgopal Venkataraman - 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, USAAllen Michael Savedra - 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, USASteven G Kernie - 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, USAAnn M Stowe - 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.eduLakshmi Raman - 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
- Resource Type
- Journal article
- Publication Details
- Journal of leukocyte biology, Vol.99(1), pp.21-29
- Publisher
- United States
- DOI
- 10.1189/jlb.5HI0914-447R
- PMID
- 26038434
- ISSN
- 0741-5400
- eISSN
- 1938-3673
- Grant note
- name: Perot Family Center for Brain; name: Children’s Medical Center Dallas; name: L.R.; name: Children’s Medical Center Dallas Foundation; name: L.R.; name: Neuro-Models Facility; name: Dept. of Neurology … Neurotherapeutics; DOI: 10.13039/100000968, name: American Heart Association; name: A. M.; name: S.B.O.; DOI: 10.13039/100011301, name: Children’s Research Institute; name: Foundation Flow Cytometry Facility
- Language
- English
- Date published
- 01/2016
- Academic Unit
- Pathology
- Record Identifier
- 9984065393202771
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