Mice lacking perforin have improved regeneration of the injured femoral nerve

Neural Regeneration Research, 2022 · DOI: https://doi.org/10.4103/1673-5374.332152 · Published: January 7, 2022

Immunology Neurology Regenerative Medicine & Stem Cells

Simple Explanation

This research investigates the role of perforin, an immune system enzyme, in nerve regeneration after injury. The study focuses on the femoral nerve in mice, comparing those with and without perforin. The study found that mice lacking perforin showed better motor recovery, more accurate nerve regrowth, and improved nerve insulation (myelination) after injury compared to normal mice. These improvements suggest perforin hinders nerve repair. The absence of perforin also resulted in fewer immune cells infiltrating the injured nerve, suggesting a tighter blood-nerve barrier. This research points to potential therapeutic strategies targeting perforin to enhance nerve regeneration after injury.

Study Duration

8 weeks

Participants

11 Pfp–/– mice and 11 wild-type control mice

Evidence Level

Not specified

Key Findings

1
Perforin-deficient mice showed better motor recovery after femoral nerve injury compared to wild-type mice, particularly at 4 and 8 weeks post-injury.
2
Retrograde tracing revealed that perforin-deficient mice had a higher number of motoneurons correctly projecting into the motor nerve branch.
3
Myelination of regrown axons was more extensive in perforin-deficient mice compared to wild-type mice, indicating improved nerve insulation.

Research Summary

This study investigates the role of perforin, an enzyme involved in immune responses, in peripheral nerve regeneration following femoral nerve injury in mice. The researchers compared perforin-deficient (Pfp–/–) mice with wild-type controls to assess motor recovery and nerve regeneration. The key findings indicate that Pfp–/– mice exhibit improved motor recovery, more accurate motoneuron reinnervation, enhanced myelination, and increased cholinergic synaptic terminals around spinal motoneurons compared to wild-type mice. The study concludes that perforin restricts motor recovery after femoral nerve injury due to decreased survival of motoneurons and reduced myelination. These findings suggest that targeting perforin could be a potential therapeutic strategy for enhancing peripheral nerve regeneration.

Practical Implications

Therapeutic Target

Perforin may be a therapeutic target for enhancing nerve regeneration after injury.

Improved Recovery

Understanding the role of the immune system, specifically perforin, can lead to better strategies for promoting nerve repair and functional recovery.

Blood-Nerve Barrier

Maintaining the integrity of the blood-nerve barrier is crucial for optimal nerve regeneration.

Study Limitations

1
Constitutional ablation of perforin could potentially cause developmental effects.
2
Lack of measurable differences in contralateral nerves between Pfp–/– and WT mice, as well as normal walking pattern in Pfp–/– mice prior to injury suggest that this scenario is not very probable.
3
A gain-of function study in Pfp–/– mice, or conditional knockout in adult mice would give a definite answer.

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