Assessing Functional Recovery of Eupneic Diaphragm Activity Following Unilateral Cervical Spinal Cord Hemisection in Rats

Obaid U. Khurram; Matthew J. Fogarty; Wen-Zhi Zhan; Carlos B. Mantilla; Gary C. Sieck

doi:10.3791/66828

Assessing Functional Recovery of Eupneic Diaphragm Activity Following Unilateral Cervical Spinal ...

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Assessing Functional Recovery of Eupneic Diaphragm Activity Following Unilateral Cervical Spinal Cord Hemisection in Rats

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05:09 min

June 14, 2024

DOI: 10.3791/66828-v

Obaid U. Khurram¹, Matthew J. Fogarty¹, Wen-Zhi Zhan¹, Carlos B. Mantilla^1,2, Gary C. Sieck^1,2

¹Department of Physiology and Biomedical Engineering,Mayo Clinic, ²Department of Anesthesiology and Perioperative Medicine,Mayo Clinic

Overview

This study investigates respiratory complications following cervical spinal cord injury (cSCI), a leading cause of mortality. Utilizing a rat model with unilateral C2 spinal hemisection (C2SH), the research aims to analyze the recovery of diaphragm muscle (DIAm) activity. It emphasizes the role of BDNF signaling in neuroplasticity and presents a method for assessing functional recovery.

Key Study Components

Area of Science

Neuroscience
Respiratory physiology
Neuroplasticity

Background

Cervical spinal cord injury significantly impacts respiratory function.
Phrenic motor neurons control diaphragm activity but are disrupted by C2SH.
Neuroplasticity allows for some recovery of diaphragm function post-injury.
High-throughput analysis techniques are essential for understanding neuromotor control.

Purpose of Study

To evaluate diaphragm muscle activity recovery after C2SH.
To clarify the role of BDNF signaling in the recovery process.
To develop a reproducible method for assessing DIAm activity in rats.

Methods Used

Electromyographic (EMG) recordings were taken from the diaphragm muscle.
The rat model underwent a unilateral C2 spinal hemisection procedure.
Pre-surgery and post-surgery evaluations monitored diaphragm EMG activity.
Specific surgical techniques were employed to access spinal structures while preserving related tissues.
Hydration and recovery protocols were established for post-operative care.

Main Results

Recovery of ipsilateral diaphragm activity occurred, highlighting neuroplasticity.
BDNF signaling through TrkB receptors was implicated in recovery mechanisms.
EMG activity demonstrated differences between anesthetized and awake conditions.
The method provided reproducibility and reliability in assessing diaphragm function.

Conclusions

The study establishes a foundational method for examining diaphragm activity recovery post-cSCI.
Insights into BDNF-mediated plasticity inform future neurological research.
This model can be crucial for understanding respiratory dysfunction in spinal cord injury contexts.

Frequently Asked Questions

What are the advantages of using this rat model?

The rat model allows for controlled physiological assessments and provides insights into diaphragm recovery processes that are relevant to human conditions.

How is the C2 spinal hemisection performed?

The procedure involves a surgical laminectomy at C2, sectioning the spinal cord while preserving neuroanatomical structures to minimize limb deficits.

What types of data are obtained from EMG recordings?

EMG recordings yield information on diaphragm muscle activity, including changes in excitability and functional recovery timelines post-injury.

How can this method be adapted for other studies?

The surgical and recording methods can be modified to study other neuromuscular junctions or muscle types in various injury models.

What key limitations should be considered?

Potential limitations include variations in recovery among individuals and the complexity of ensuring accurate EMG recordings in awake animals.

Respiratory complications are the leading cause of death in individuals with cervical spinal cord injury (cSCI). Animal models of cSCI are essential for mechanistic evaluations and pre-clinical studies. Here, we introduce a reproducible method to assess functional recovery of diaphragm muscle (DIAm) activity following unilateral C₂ spinal hemisection (C₂SH) in rats.

Our research focuses on neuromotor control of the diaphragm muscle during breathing. Phrenic motor neurons innervating diaphragm muscle fibers receive descending excitatory input from the brainstem, which is primarily ipsilateral, and, therefore, disrupted by upper cervical spinal cord hemisection or C2SH. Following C2SH, there is spontaneous recovery of ipsilateral diaphragm activity, reflecting neuroplasticity.

A major development is demonstrating the role of brain-derived neurotropic factor or BDNF signaling through its high-affinity TrkB receptor in the recovery of diaphragm activity Following C2SH. A second development is the use of machine learning approaches to facilitate high-throughput analyses of diaphragm activity during numerous respiratory cycles. The lack of reliable, unbiased, high-throughput techniques to evaluate basic elements of diaphragm neuromotor control is a challenge in defining recovery of function.

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