Publications

Latest publication 06/02/2015

Perinatal chronic hypoxia induces cortical inflammation- hypomyelination- and pe

pCH is an important risk factor for brain injury and long-term morbidity in children, occurring during the developmental stages of neurogenesis,...

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    [title] => Perinatal chronic hypoxia induces cortical inflammation- hypomyelination- and pe
    [paragraph] => Perinatal chronic hypoxia induces cortical inflammation, hypomyelination, and peripheral myelin-specific T cell autoreactivity
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Authors
Ortega SB, Kong X, Venkataraman R, Savedra AM, Kernie SG, Stowe AM, Raman L

 Lab
Departments of *Neurology and Neurotherapeutics and Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA; 
Journal
J Leukoc Biol.
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.
BIOSEB Instruments Used
Aron Test or Four Plates Test (LE830),Rotarod (BX-ROD)
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The Aron test allows a quick characterization of putative anxiolytics compounds in naïve animals. A must for studying anxiety, drug screening and phenotyping.
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