Mid-cervical interneuron networks following high cervical spinal cord injury

Respir Physiol Neurobiol, 2020 · DOI: 10.1016/j.resp.2019.103305 · Published: January 1, 2020

Simple Explanation

This study examines how spinal interneurons (INs) in the mid-cervical region of the spinal cord respond after a spinal cord injury (SCI) at the C2 level, specifically focusing on the connections between these INs and how they are affected by low oxygen levels (hypoxia). The researchers explored how these IN networks might contribute to recovery after SCI. The research involved recording the activity of INs on both sides of the spinal cord in rats that had experienced a C2 hemisection (C2Hx) injury. They analyzed the direction and strength of synaptic connections between INs, looking at whether signals primarily traveled from the uninjured side to the injured side of the spinal cord. The findings suggest that after a SCI, INs can form connections that help relay signals around the injury site, especially from the contralateral (uninjured) side to the ipsilateral (injured) side. Also, the acute exposure to hypoxia can change the connectivity of these INs, which may contribute to neuroplasticity and recovery.

Study Duration

12-16 weeks post-injury

Participants

8 adult female Sprague-Dawley rats

Evidence Level

Not specified

Key Findings

1
During baseline recordings, the majority of detectable excitatory IN connections occurred in a contra- to- ipsilateral direction, suggesting that signals tend to flow from the uninjured side of the spinal cord to the injured side.
2
Acute respiratory stimulation with hypoxia abolished the directionality of excitatory connections and simultaneously increased the detectable inhibitory connections within the ipsilateral cord, indicating hypoxia can modulate IN connectivity.
3
Interneurons recorded ipsilateral to C2Hx fired at higher rates when compared to INs in the contralateral spinal cord, suggesting that the injured side of the spinal cord exhibits more activity.

Research Summary

This study investigates the synaptic connectivity of mid-cervical interneurons (INs) following a C2 hemisection (C2Hx) spinal cord injury (SCI) in rats, focusing on the directionality of connections and the impact of acute hypoxia. The key findings indicate a predominance of contralateral-to-ipsilateral excitatory connections during baseline conditions, which is abolished by acute hypoxia, and an increase in inhibitory connections within the ipsilateral spinal cord during hypoxia. These results suggest that propriospinal networks caudal to SCI exhibit a contralateral-to-ipsilateral directionality of synaptic connections and that these connections are modulated by acute exposure to hypoxia, supporting the hypothesis that synaptic information is relayed across the spinal midline after injury.

Practical Implications

Neurorehabilitation Strategies

These findings suggest that targeting spinal interneurons may be a viable therapeutic approach for promoting recovery after spinal cord injury. Neurorehabilitation strategies may focus on utilizing the neuroplastic potential of segmental and propriospinal INs.

Hypoxia-Based Therapies

The study supports the use of brief exposures to hypoxia as a means of enhancing respiratory, somatic, and sympathetic motor output, leveraging the dynamic remodeling of mid-cervical networks.

Directionality of Spinal Information

The research provides evidence for the 'directionality' of segmental IN connections, which supports the hypothesis that synaptic information can be relayed across the spinal midline to activate silent circuits after unilateral SCI. This suggests novel targets for therapeutic intervention to enhance motor recovery.

Study Limitations

1
The study was conducted on adult female Sprague-Dawley rats, limiting generalizability to other populations.
2
The sample size of 8 rats may limit the statistical power of some analyses.
3
The absence of evidence of pre-phrenic INs is not, in fact, evidence of absence

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