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Article Abstract
Aims: Fibrotic scars composed of a dense extracellular matrix are the major obstacles for axonal regeneration. Previous studies have reported that antitumor drugs promote neurofunctional recovery.
Methods: We investigated the effects of 5-fluorouracil (5-FU), a classical antitumor drug with a high therapeutic index, on fibrotic scar formation, axonal regeneration, and functional recovery after spinal cord injury (SCI).
Results: 5-FU administration after hemisection SCI improved hind limb sensorimotor function of the ipsilateral hind paws. 5-FU application also significantly reduced the fibrotic scar formation labeled with aggrecan and fibronectin-positive components, Iba1 /CD11b macrophages/microglia, vimentin, chondroitin sulfate proteoglycan 4 (NG2/CSPG4), and platelet-derived growth factor receptor beta (PDGFRβ) pericytes. Moreover, 5-FU treatment promoted stromal cells apoptosis and inhibited fibroblast proliferation and migration by abrogating the polarity of these cells and reducing matrix metalloproteinase 9 expression and promoted axonal growth of spinal neurons via the neuron-specific protein doublecortin-like kinase 1 (DCLK1). Therefore, 5-FU administration impedes the formation of fibrotic scars and promotes axonal regeneration to further restore sensorimotor function after SCI.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9627390 | PMC |
| http://dx.doi.org/10.1111/cns.13930 | DOI Listing |
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