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

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)