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The Journal of Neuroscience, April 1, 2002, 22(7):2792-2803
NG2 Is a Major Chondroitin Sulfate Proteoglycan Produced
after Spinal Cord Injury and Is Expressed by Macrophages and
Oligodendrocyte Progenitors
Leonard L.
Jones1,
Yu
Yamaguchi2,
William B.
Stallcup2, and
Mark H.
Tuszynski1, 3
1 Department of Neurosciences, University of
California, San Diego, La Jolla, California 92093, 2 The
Burnham Institute, La Jolla, California 92037, and
3 Veterans Affairs Medical Center, San Diego, California
92161
Several extracellular matrix (ECM) molecules have been identified
as potent inhibitors of neurite outgrowth in vitro and
are believed to limit axonal growth after CNS injury. Recent studies have shown that different members of the chondroitin sulfate
proteoglycan (CSPG) class of putatively inhibitory ECM molecules are
expressed after a number of CNS injuries. The purpose of this study was to evaluate the relative amounts of individual CSPGs expressed after
spinal cord injury (SCI) and identify their cells of origin. Evaluation
of total soluble CSPGs 2 weeks after dorsal column lesion in the rat
demonstrated that NG2 is highly upregulated and is a major CSPG
species. Immunocytochemical analysis further demonstrated that NG2
expression is upregulated within 24 hr of injury, peaks at 1 week, and
remains elevated for at least an additional 7 weeks. NG2 expression
results from a multicellular response to injury, including both
reactive macrophages and oligodendrocyte progenitors; astrocytes were
not identified as a major source of NG2. Immunocytochemical analysis of
other CSPG family members 7 d after injury showed moderate
upregulation of versican, brevican, and neurocan, and downregulation of
phosphacan. Axonal tracing experiments demonstrated dense NG2 labeling
adjacent to the forward processes of transected corticospinal tract
axons in a spatial profile that could restrict axonal growth. Thus, NG2
is a major component of this putatively inhibitory class of ECM
molecules expressed at sites of SCI and may restrict axonal regeneration.
Key words:
NG2; spinal cord injury; chondroitin sulfate
proteoglycan; macrophage; corticospinal tract; inhibition; regeneration; astrocytes
Copyright © 2002 Society for Neuroscience 0270-6474/02/2272792-12$05.00/0
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[Full Text]
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|
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[Full Text]
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[Full Text]
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|