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 language | English |
---|---|
Pages (from-to) | 21-29 |
Number of pages | 9 |
Journal | Journal of Leukocyte Biology |
Volume | 99 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2016 |
Bibliographical note
Publisher Copyright:© Society for Leukocyte Biology.
Keywords
- CD4 T cells
- Motor function
- Myelination
- Oligodendrocyte progenitors
- Periventricular leukomalacia
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Cell Biology