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

CNS Neurosci Ther, 2022 · DOI: 10.1111/cns.13930 · Published: July 1, 2022

Spinal Cord Injury Pharmacology Neurology

Simple Explanation

This study investigates the use of 5-fluorouracil (5-FU), a common anti-cancer drug, to reduce scar tissue formation after spinal cord injury (SCI) in rats. The researchers found that 5-FU treatment improved motor function and reduced the size of fibrotic scars in rats with SCI. The drug appears to work by reducing the activity of certain proteins (MMP9) and stabilizing structures (microtubules) within cells, which are involved in scar formation.

Study Duration

4 weeks

Participants

Adult female Sprague Dawley (SD) rats

Evidence Level

Not specified

Key Findings

1
5-FU administration after spinal cord injury improved hind limb sensorimotor function.
2
5-FU treatment significantly reduced fibrotic scar formation by reducing components such as aggrecan and fibronectin.
3
5-FU promotes axonal growth of spinal neurons via the neuron-specific protein doublecortin-like kinase 1 (DCLK1).

Research Summary

This study investigated the effect of 5-FU on fibrotic scar formation after SCI, finding that it reduces scarring by inhibiting MMP9 and stabilizing microtubules. The study demonstrates that 5-FU administration reduces components of fibrotic scar and promotes axonal regeneration. The key mechanism of 5-FU is reducing the fibronectin+, CD11b+ and GFAP+ cells accumulation at the onset of the acute phase.

Practical Implications

Potential Therapeutic Strategy

5-FU could be a novel therapeutic for clinical treatment of SCI by reducing fibrotic scar formation and promoting axonal regeneration.

Drug Repurposing

Repurposing an existing drug like 5-FU could offer a faster and more cost-effective approach to SCI treatment.

Further Research

Further studies are warranted to investigate the long-term effects and optimal dosage of 5-FU for SCI treatment, as well as potential side effects.

Study Limitations

1
Only female rats were used, limiting the generalizability of the findings to both sexes.
2
The study focuses on a hemisection SCI model, which may not fully represent other types of SCI.
3
The long-term effects of 5-FU administration were not fully investigated.

Your Feedback

Was this summary helpful?

Back to Spinal Cord Injury