Efficacy of nonviral gene transfer of human hepatocyte growth factor (HGF) against ischemic-reperfusion nerve injury in rats

PLOS ONE, 2020 · DOI: https://doi.org/10.1371/journal.pone.0237156 · Published: August 11, 2020

Cardiovascular Science Neurology Genetics

Simple Explanation

Ischemic neuropathy, nerve damage due to lack of blood flow, is a common issue, especially in individuals with poor circulation in their limbs. This condition can lead to chronic pain that is difficult to manage, even after blood flow is restored. This study used a rat model to investigate whether hepatocyte growth factor (HGF) gene transfer could help alleviate ischemic neuropathy caused by ischemia-reperfusion nerve injury (IRI). The results showed that HGF gene transfer improved nerve function, increased blood vessel growth, and reduced pain-related molecules in the affected nerves, suggesting HGF gene transfer as a potential treatment for ischemic neuropathy.

Study Duration

8 weeks

Participants

108 male Wistar rats, weighing 220–280 g, age 8–9 weeks

Evidence Level

Not specified

Key Findings

1
HGF gene transfer significantly improved mechanical allodynia and thermal hyperalgesia in rats with ischemic-reperfusion nerve injury (IRI).
2
HGF gene transfer resulted in a significant increase in the density of endoneurial microvessels in both sciatic and tibial nerves, promoting neovascularization.
3
HGF gene transfer reduced the elevated mRNA levels of P2X3 and P2Y1 receptors, and transient receptor potential vanilloid receptor subtype 1 (TRPV1) in sciatic nerves, dorsal root ganglia, and spinal cord.

Research Summary

This study investigated the efficacy of nonviral retrograde gene transfer of human hepatocyte growth factor (HGF) in improving ischemic neuropathy using a rat model of ischemic-reperfusion nerve injury (IRI). The results demonstrated that HGF gene transfer led to significant improvements in mechanical allodynia, thermal hyperalgesia, skin blood flow and temperature, and sciatic nerve conduction parameters. The study concludes that HGF gene transfer is a promising candidate for the treatment of acute ischemic nerve injury caused by reperfusion injury due to its potent angiogenesis and enhanced nerve regeneration properties.

Practical Implications

Therapeutic Potential

HGF gene transfer may be a viable therapeutic strategy for treating acute ischemic neuropathy caused by reperfusion injury.

Angiogenesis and Nerve Regeneration

The study highlights the importance of angiogenesis and nerve regeneration in the treatment of ischemic nerve injuries, suggesting HGF as a key factor in promoting these processes.

Pain Management

HGF gene transfer could provide an effective approach for managing neuropathic pain associated with ischemic conditions by modulating specific receptors and ion channels.

Study Limitations

1
The study was conducted on a rat model, and the results may not be directly applicable to humans.
2
The molecular mechanism of retrograde transport of HGF is not fully understood.
3
Further research is needed to optimize the delivery method and dosage of HGF gene transfer for clinical applications.

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