5-Fluorouracil Reduces the Fibrotic Scar Via Inhibiting Matrix Metalloproteinase 9 and Stabilizing Microtubules After Spinal Cord Injury

Overview

Journal CNS Neurosci Ther

Specialties Neurology
Pharmacology

Date 2022 Aug 3

PMID 35918897

Authors

Yang Xu

Xiuying He

Yangyang Wang

Jiao Jian

Xia Peng

Lie Zhou

Yi Kang

Tinghua Wang

Affiliations

Soon will be listed here.

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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5-Fluorouracil reduces the fibrotic scar via inhibiting matrix metalloproteinase 9 and stabilizing microtubules after spinal cord injury.

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