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  4. Effects of local and systemic treatment with human natural killer-1 mimetic peptide (HNK-1) after ventral root avulsion and reimplantation in mice

Effects of local and systemic treatment with human natural killer-1 mimetic peptide (HNK-1) after ventral root avulsion and reimplantation in mice

J Venom Anim Toxins incl Trop Dis, 2024 · DOI: 10.1590/1678-9199-JVATITD-2023-0065 · Published: May 20, 2024

Spinal Cord InjuryRegenerative MedicineNeurology

Simple Explanation

Spinal ventral root injuries lead to motoneuron degeneration, hindering functional recovery. This study comparatively investigates the effects of local administration of an HNK-1 mimetic peptide (mp-HNK-1) and systemic treatment with ursolic acid (UA) after ventral root avulsion and reimplantation with heterologous fibrin biopolymer (HFB). The experiment involved dividing female mice into five groups: Avulsion, Reimplantation, mp-HNK-1 (in situ), and UA (systemic treatment). The mice were then evaluated 2 and 12 weeks after surgery using functional assessments and analyses of neuronal survival, glial reactions, and synaptic coverage. Ursolic acid (UA) shows promise as a treatment for nerve injuries due to its neuroprotective, antioxidant, and immunomodulatory effects. It promotes motor and sensory recovery, reduces microglial reactions, and decreases reactive astrogliosis, offering a potential therapeutic approach for spinal ventral root injuries.

Study Duration
12 weeks
Participants
8-week-old female C57BL/6JUnib mice
Evidence Level
Not specified

Key Findings

  • 1
    UA treatment led to long-term neuroprotection, decreasing microglial reactions and reactive astrogliosis.
  • 2
    UA increased glutamatergic and GABAergic inputs in the ventral spinal cord two weeks after injury, preceding its neuroprotective effects.
  • 3
    Functional analysis revealed that UA treatment improved motor and sensory recovery.

Research Summary

This study investigated the effects of local mp-HNK-1 and systemic UA treatments following ventral root avulsion and reimplantation in mice. UA treatment showed long-term neuroprotection, reduced glial reactions, and improved functional recovery, while mp-HNK-1 had no significant effects. The findings suggest UA's potential as a therapeutic agent for spinal root injuries by modulating glial activity and synaptic maintenance.

Practical Implications

Therapeutic Potential

Ursolic acid may be a viable therapeutic option for spinal cord injuries involving ventral root avulsion.

Glial Modulation

Treatments targeting glial cell activity could enhance recovery after nerve injuries.

Synaptic Maintenance

Maintaining synaptic inputs in axotomized motoneurons is crucial for functional recovery.

Study Limitations

  • 1
    The single local application of mp-HNK-1 did not demonstrate long-term neuroprotective effects.
  • 2
    The study was conducted on female mice, and results may vary in male subjects.
  • 3
    Further research is needed to elucidate the precise mechanisms of UA's neuroprotective effects.

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