Noradrenergic Components of Locomotor Recovery Induced by Intraspinal Grafting of the Embryonic Brainstem in Adult Paraplegic Rats

International Journal of Molecular Sciences, 2020 · DOI: 10.3390/ijms21155520 · Published: August 1, 2020

Spinal Cord Injury Neurology Rehabilitation

Simple Explanation

This study investigates whether neurons other than serotonergic (5-HT) neurons contribute to locomotor recovery in paraplegic rats after spinal cord injury. Specifically, the study focuses on the role of noradrenergic (NA) neurons in this recovery process. The researchers transplanted embryonic brainstem tissue into the sub-lesional spinal cord of adult rats after a complete spinal cord transection. They then tested the locomotor performance of these rats, along with control rats, using electromyographic recordings from hindlimb muscles. The study found that noradrenergic innervation, in addition to serotonergic innervation, plays a significant role in enhancing hindlimb movement in paraplegic rats after intraspinal grafting of brainstem embryonic tissue.

Study Duration

Two months

Participants

Adult paraplegic rats

Evidence Level

Not specified

Key Findings

1
Morphological analysis revealed the presence of tyrosine hydroxylase positive (NA) neurons in addition to 5-HT neurons in the host spinal cords of grafted rats.
2
Yohimbine (α2 adrenergic receptor antagonist) facilitated locomotor abilities in spinal grafted rats, while clonidine (α2 adrenergic receptor agonist) suppressed them.
3
The distribution of NA fibers was limited to the central canal and intermediolateral zone, while 5-HT fibers innervated a broader range of spinal cord areas.

Research Summary

This study demonstrates that noradrenergic innervation plays a significant role in locomotor recovery in paraplegic rats after intraspinal grafting of embryonic brainstem tissue, complementing the well-established role of serotonergic innervation. The researchers found that α2 adrenergic receptors are involved in the action of 5-HT/NA systems in the locomotor recovery of spinal grafted rats, with yohimbine improving locomotion and clonidine abolishing it. The study proposes direct and indirect mechanisms of 5-HT and NA interaction that can be responsible for the locomotor recovery after intraspinal grafting.

Practical Implications

Therapeutic potential

The findings suggest that targeting noradrenergic pathways, in addition to serotonergic pathways, could enhance the effectiveness of cell transplantation therapies for spinal cord injury.

Understanding neural mechanisms

The study provides insights into the complex interplay of neurotransmitter systems in locomotor recovery after spinal cord injury, which can inform the development of more targeted interventions.

Optimizing grafting strategies

The research suggests that grafts containing both serotonergic and noradrenergic neurons may be more effective in promoting locomotor recovery than grafts containing only serotonergic neurons.

Study Limitations

1
The study was conducted on rats, and the results may not be directly applicable to humans.
2
The exact mechanisms by which noradrenergic innervation contributes to locomotor recovery remain to be fully elucidated.
3
The study focused on α2 adrenergic receptors, and further research is needed to investigate the role of other adrenergic receptor subtypes.

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