Methotrexate combined with methylprednisolone for the recovery of motor function and differential gene expression in rats with spinal cord injury

Neural Regeneration Research, 2017 · DOI: 10.4103/1673-5374.215263 · Published: September 1, 2017

Spinal Cord Injury Pharmacology Regenerative Medicine

Simple Explanation

This study investigates the combined effects of methotrexate (MTX) and methylprednisolone (MP) on spinal cord injury (SCI) recovery in rats. SCI often leads to primary and secondary injuries, with inflammation worsening the damage. MP is a common treatment, but high doses have side effects. MTX has anti-inflammatory properties and may reduce inflammation after SCI. The research analyzes how MTX combined with MP affects gene expression and molecular mechanisms in SCI treatment using a rat model. The combination aims to improve motor function recovery and reduce inflammation. Rats were treated with MP and MTX after SCI, and their motor function was assessed using gait analysis. Gene expression changes were analyzed using high-throughput sequencing to understand the molecular mechanisms of the combined treatment compared to MP alone.

Study Duration

8 Weeks

Participants

50 male Sprague-Dawley rats

Evidence Level

Not specified

Key Findings

1
The study found that methotrexate (MTX) combined with methylprednisolone (MP) significantly improved motor function in rats with spinal cord injury (SCI). Gait analysis showed improvements in hind limb swing time, stride time, minimum longitudinal deviation, instant speed, footprint area, and regularity index at 4 and 8 weeks post-injury.
2
High-throughput sequencing revealed differential expression of 316 genes in the injured spinal cord treated with the combined therapy compared to MP alone. 275 genes were up-regulated and related to nerve recovery, anti-oxidative, anti-inflammatory, and anti-apoptotic functions. 41 genes were down-regulated and related to proinflammatory and pro-apoptotic functions.
3
The combination of MTX and MP exhibited better effects on inhibiting inflammatory cytokines and enhancing antioxidant and anti-apoptotic effects compared to MP alone. This enhanced neuroprotection suggests that the differentially expressed genes play a crucial role in the recovery processes.

Research Summary

This study investigates the therapeutic effects of combining methotrexate (MTX) and methylprednisolone (MP) on spinal cord injury (SCI) in rats. High doses of MP can cause side effects, while MTX has anti-inflammatory and immunosuppressive properties. The study aimed to analyze gene expression changes and molecular mechanisms of the combined treatment. Rats with SCI were treated with MP and MTX, and gait analysis was performed to assess motor function. High-throughput sequencing was used to analyze differential gene expression compared to MP alone. The results showed that the combined treatment significantly improved motor function. The combined therapy exhibited better effects on inhibiting inflammatory cytokines and enhancing antioxidant and anti-apoptotic effects, leading to stronger neuroprotective effects than MP alone. These findings offer potential new strategies for managing SCI.

Practical Implications

Enhanced Neuroprotection

Combining MTX with MP provides enhanced neuroprotective effects compared to MP alone, potentially improving patient outcomes.

Inflammation and Apoptosis Control

The combined therapy effectively inhibits inflammatory cytokines and enhances antioxidant and anti-apoptotic effects, which are critical for SCI recovery.

Novel Therapeutic Strategies

This study provides new strategies for controlling SCI by using the combination of MTX and MP, which can be further explored in clinical settings.

Study Limitations

1
The complexity and variety of differentially expressed genes require in-depth research.
2
The specific mechanism of action of MP and MTX combination needs further examination.
3
Not specified

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