Open Access5‐Fluorouracil reduces the fibrotic scar via inhibiting matrix metalloproteinase 9 and stabilizing microtubules after spinal cord injury
Author(s) -
Xu Yang,
He Xiuying,
Wang Yangyang,
Jian Jiao,
Peng Xia,
Zhou Lie,
Kang Yi,
Wang Tinghua
Publication year - 2022
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.13930
Subject(s) - regeneration (biology) , scars , glial scar , fibronectin , spinal cord injury , extracellular matrix , microbiology and biotechnology , cancer research , chondroitin sulfate proteoglycan , wound healing , medicine , pathology , spinal cord , chemistry , immunology , biology , proteoglycan , psychiatry
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.