Meningeal cells and glia establish a permissive environment for axon regeneration after spinal cord injury in newts

Neural Development, 2011 · DOI: 10.1186/1749-8104-6-1 · Published: January 4, 2011

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Newts can regenerate their spinal cords after injury, unlike mammals. This study examines how this happens after a complete spinal cord transection, which is more relevant to human spinal cord injury than tail amputation studies. The study identifies stages of axon regeneration in newts following spinal cord transection. It highlights the role of meningeal cells and glia in creating a permissive environment for axon regrowth. Unlike mammals, where these cells form inhibitory barriers, in newts, meningeal cells and glia interact to facilitate axon regeneration across the injury site, even in the presence of inflammation.

Study Duration

1 day to 9 weeks

Participants

71 adult newts (Notophthalmus viridescens)

Evidence Level

Not specified

Key Findings

1
Axon regeneration following spinal cord transection involves six stages: retraction, growth initiation, wrapping, wisping, spiking, and contact and growth beyond the injury site.
2
Meningeal and endothelial cells regenerate into the lesion first, associated with a loose extracellular matrix (ECM) containing both permissive and inhibitory proteins, which allows axon growth cone migration.
3
Ascending axons regenerate, but sensory axons do not appear to be among them, and the entire regenerative process occurs despite an inflammatory response.

Research Summary

This study details the cellular and extracellular events during newt spinal cord regeneration after transection injury. It emphasizes the crucial role of meningeal and glial cells in promoting axon regeneration. The researchers observed that, unlike in mammals where these cells create inhibitory barriers, newt meningeal and glial cells interact to form a permissive environment. Key findings include the identification of specific stages of axon regeneration, the involvement of meningeal and endothelial cells in forming a permissive ECM, and the observation that sensory axons do not appear to regenerate.

Practical Implications

Therapeutic Approaches

Identifying mechanisms underlying the permissive behaviors of meningeal and glial cells in newts could inform new therapeutic approaches for improving spinal cord regeneration in mammals.

Understanding ECM

Further research on the ECM composition and its regulation in newt spinal cord regeneration can offer insights into manipulating the ECM environment in mammalian SCI to promote regeneration.

Glia-Meningeal Cell Interaction

The glia-meningeal cell interaction model proposed in this study opens avenues for exploring targeted interventions to modulate these cell interactions and foster a regenerative environment in mammalian SCI.

Study Limitations

1
The ages of the adult newts used in this study were unknown, which could introduce variability in regeneration rates.
2
The axon tracer used fades out after 3 to 4 mm, making it difficult to correlate the distance axons regenerated beyond the injury site with functional recovery.
3
Cell-type specific antibodies did not produce a reliable signal in the newt preparations, which made it difficult to definitively identify specific inflammatory cell types.

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