Serotonergic pharmacotherapy promotes cortical reorganization after spinal cord injury

Exp Neurol, 2013 · DOI: 10.1016/j.expneurol.2012.12.004 · Published: March 1, 2013

Spinal Cord Injury Pharmacology Neurology

Simple Explanation

After a spinal cord injury, the brain can reorganize itself, potentially aiding recovery. This study investigates whether using drugs that affect serotonin (5-HT) can influence this reorganization. Rats with complete spinal cord injuries were given different doses of 5-HT agonists. The results showed that the drugs promoted more brain reorganization than the injury alone. The extent of brain reorganization was linked to how well the rats recovered their ability to move, suggesting that the drug's direct effects on the brain and indirect effects due to improved movement both play a role.

Study Duration

8 weeks

Participants

24 adult female Sprague-Dawley rats

Evidence Level

Level 2: Experimental study using a complete spinal transection model in rats.

Key Findings

1
Chronic 5-HT pharmacotherapy increased the proportion of cells that responded to stimulation above the level of the lesion in both the HLSM cortex and the FLM cortex.
2
The high dose group had a larger proportion of responding cells than the control group for both the HLSM and FLM cortices.
3
Cortical reorganization was well correlated to behavioral improvement such that animals that achieved weight support had the greatest extent of cortical reorganization.

Research Summary

This study demonstrates that 5-HT pharmacotherapy after a complete spinal transection in the adult rat produced more reorganization in the sensorimotor cortex than would be expected by the transection alone. Cortical responses evoked by stimuli delivered above the level of the lesion markedly increased after therapy in a dose-dependent manner, both in the number of responsive cells and in the magnitude of responsive cells. Cortical reorganization was well correlated to behavioral improvement such that animals that achieved weight support had the greatest extent of cortical reorganization.

Practical Implications

Therapeutic Potential

Serotonergic pharmacotherapy could be a valuable tool in promoting cortical reorganization and functional recovery after spinal cord injury.

Dose Optimization

The dose-dependent nature of the reorganization suggests the importance of optimizing the dosage of 5-HT agonists for maximal therapeutic effect.

Combination Therapy

The interplay between direct drug effects and indirect effects from behavioral improvement suggests a potential benefit from combining pharmacotherapy with rehabilitative strategies.

Study Limitations

1
The study was conducted on rats and may not directly translate to humans.
2
The complete transection model does not fully represent the range of spinal cord injuries seen in clinical settings.
3
The neuroanatomical substrates of the cortical reorganization remain unclear.

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