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  4. Source of Early Regenerating Axons in Lamprey Spinal Cord Revealed by Wholemount Optical Clearing with BABB

Source of Early Regenerating Axons in Lamprey Spinal Cord Revealed by Wholemount Optical Clearing with BABB

Cells, 2020 · DOI: 10.3390/cells9112427 · Published: November 6, 2020

Spinal Cord InjuryRegenerative MedicineNeurology

Simple Explanation

This paper investigates the origins of axons that regenerate early after spinal cord injury in lampreys. Researchers used a tissue clearing technique called BABB to enhance the resolution of neuronal structures in wholemounts of the lamprey central nervous system. By combining BABB clearing with fluorescent labeling, they identified that many of the early regenerating axons originate from small neurons in the brainstem. They also found that some propriospinal neurons located near the injury site contribute to early regeneration. The early regenerating axons were of small caliber and showed little retraction after injury. This study provides insights into the mechanisms of axon regeneration and functional recovery after spinal cord injury.

Study Duration
3 days to 13 weeks post-TX
Participants
Larval sea lampreys (Petromyzon marinus), 9–12 cm in length (3–4 years old)
Evidence Level
Not specified

Key Findings

  • 1
    Over 50% of the early regenerating axons belonged to small neurons in the brainstem, specifically in the posterior and middle rhombencephalic reticular nuclei (PRRN and MRRN).
  • 2
    Some propriospinal neurons located close to the TX also contributed to early regeneration, but their numbers decreased with distance from the original lesion.
  • 3
    Compared with axotomized giant axons, the early regenerating axons were of small caliber and showed little retraction, probably because they resealed rapidly after injury.

Research Summary

The study aimed to identify the origins of early regenerating axons in lampreys after spinal cord injury, as these axons contribute to early functional recovery. BABB clearing significantly improved the resolution of neuronal structures in wholemounts, allowing for better visualization and analysis of regenerating axons. The results showed that early regenerating axons originate primarily from small neurons in the brainstem and, to a lesser extent, from propriospinal neurons near the injury site. These axons exhibit minimal retraction and contribute to early functional recovery.

Practical Implications

Improved Imaging Techniques

BABB clearing can be used to improve the visualization of neuronal structures in wholemount preparations, enhancing the study of axon regeneration and other neurological processes.

Targeted Therapeutic Strategies

Identifying the sources of early regenerating axons can lead to the development of targeted therapeutic strategies to promote axon regeneration and functional recovery after spinal cord injury.

Understanding Axon Regeneration Mechanisms

The findings provide insights into the mechanisms of axon regeneration, particularly the role of small neurons and rapid resealing in early regeneration processes.

Study Limitations

  • 1
    BABB clearing caused tissue shrinkage, which could potentially affect the accuracy of measurements.
  • 2
    FLICA labeling did not survive the BABB clearing protocol, limiting the ability to simultaneously image apoptotic neurons and regenerating axons.
  • 3
    The study focused on early regeneration events, and further research is needed to investigate the long-term effects of these early regenerating axons on functional recovery.

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