Serotonergic Innervation of the Caudal Spinal Stump in Rats After Complete Spinal Transection: Effect of Olfactory Ensheathing Glia

J. Comp. Neurol., 2009 · DOI: 10.1002/cne.22080 · Published: August 20, 2009

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This study investigates the presence of serotonin (5-HT)-immunoreactive axons in the caudal stump of rats after complete spinal cord transection. The presence of these axons has been used as evidence of axonal regeneration in previous studies. The researchers hypothesized that olfactory ensheathing glia (OEG) transplantation, known to improve hindlimb locomotion, would result in more 5-HT-positive axons in the caudal stump compared to media-injected rats. They found that many 5-HT-labeled axons are present throughout the caudal stump of both groups. The study also examined whether 5-HT-positive axons interact with cholinergic neurons associated with motor functions. They discovered more 5-HT-positive varicosities near central canal cluster cells in OEG-injected rats, suggesting this interaction might contribute to locomotor improvement.

Study Duration

7 months

Participants

12 adult female Wistar Hannover rats

Evidence Level

Not specified

Key Findings

1
Many 5-HT-labeled axons are present throughout the caudal stump of both media- and OEG-injected rats after complete spinal cord transection, suggesting the presence of 5-HT-labeled fibers is not a reliable indicator of regeneration.
2
Occasional 5-HT-positive interneurons were found in the caudal stump, indicating a likely source of 5-HT-labeled axons independent of raphespinal regeneration.
3
OEG-injected rats showed more 5-HT-positive varicosities in lamina X adjacent to central canal cluster cells in lumbar and sacral segments compared to media-injected rats, suggesting a potential mechanism for locomotor improvement.

Research Summary

This study investigates serotonergic innervation in the caudal spinal stump of rats after complete spinal transection, focusing on the impact of olfactory ensheathing glia (OEG) transplantation. The research demonstrates that the presence of 5-HT-labeled axons in the caudal stump is not a reliable indicator of raphespinal regeneration, as these axons are present in both media- and OEG-injected rats and can originate from local interneurons. The study reveals that OEG transplantation leads to an increase in 5-HT-positive varicosities near motor-associated cholinergic neurons, particularly central canal cluster cells, suggesting a potential mechanism for the locomotor improvements observed with OEG treatment.

Practical Implications

Re-evaluation of Regeneration Markers

The presence of 5-HT-labeled fibers in the caudal stump should not be solely relied upon as evidence of raphespinal regeneration.

Targeted Therapeutic Strategies

Therapeutic interventions could focus on modulating the interaction between serotonergic axons and cholinergic interneurons to enhance locomotor recovery after spinal cord injury.

Further Investigation of OEG Mechanisms

Future research should further explore how OEG transplantation promotes the reorganization of serotonergic axons and their interaction with spinal locomotor networks.

Study Limitations

1
The study did not distinguish between serotonergic synaptic contacts and nonsynaptic associations.
2
The precise origin of 5-HT-labeled axons in the caudal stump was not definitively determined.
3
The study acknowledges that other neurotransmitter systems may also contribute to locomotor recovery.

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