期刊
EXPERIMENTAL NEUROLOGY
卷 192, 期 1, 页码 11-24出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2004.05.038
关键词
demyelination; remyelination; Nkx2.2; NG2; oligodendrocyte precursor cell; radial glia
资金
- NCRR NIH HHS [P20 RR015576, RR15576, P20 RR015576-04] Funding Source: Medline
- NINDS NIH HHS [P01 NS038665, NS38665, P01 NS038665-040003] Funding Source: Medline
Chronic demyelination is a pathophysiologic component of compressive spinal cord injury (SCI) and a characteristic finding in demyelinating diseases including multiple sclerosis (MS). A better characterization of endogenous cells responsible for successful remyelination is essential for designing therapeutic strategies aimed at restoring functional myelin. The present study examined the spatiotemporal response of endogenous oligodendrocyte precursor cells (OPCs) following ethidium. bromide (EB)-induced demyelination of the adult rat spinal cord. Beginning at 2 days post-EB injection (dpi), a robust mobilization of highly proliferative NG2(+) cells within the lesion was observed, none of which expressed the oligodendrocyte lineage-associated transcription factor Nkx2.2. At 7 dpi, a significant upregulation of Nkx2.2 by OPCs within the lesion was observed, 90% of which coexpressed NG2 and virtually all of which coexpressed the bHLH transcription factor Olig2. Despite successful recruitment of Nkx2.2(+)/Olig2(+) OPCs within the lesion, demyelinated axons were not remyelinated by these OPCs in regions lacking astrocytes. Rather, Schwann cell remyelination predominated throughout the central core of the lesion, particularly around blood vessels. Oligodendrocyte remyelination was observed in the astrogliotic perimeter, suggesting a necessary role for astrocytes in oligodendrocyte maturation. In addition, reexpression of the radial glial antigen, RC-I, by reactive astrocytes and ependymal cells was observed following injury. However, these cells did not express the neural stem cell (NSC)-associated transcription factors Sox1 or Sox2, suggesting that the endogenous response is primarily mediated by glial progenitors. In vivo electrophysiology demonstrated a limited and unsustained functional recovery concurrent with endogenous remyelination following EB-induced lesions. (C) 2004 Elsevier Inc. All rights reserved.
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