Development of a Spinal Cord Injury Model Permissive to Study the Cardiovascular Effects of Rehabilitation Approaches Designed to Induce Neuroplasticity

Biology, 2021 · DOI: 10.3390/biology10101006 · Published: October 7, 2021

Spinal Cord Injury Cardiovascular Science Neuroplasticity

Simple Explanation

People living with high-level spinal cord injury experience worse cardiovascular health than the general population. Recently, therapies that aim to increase the strength of connections in these remaining pathways have shown great potential in restoring walking, hand, and breathing function in the spinal cord injured population. In order to test these therapies for their effects on cardiovascular function, we developed a new type of spinal cord injury rat model that spares enough pathways for these therapies to act upon but still produces measurable reductions in heart and blood vessel function that can be targeted with interventions/treatments.

Study Duration

2 weeks

Participants

26 male Wistar rats

Evidence Level

Not specified

Key Findings

1
SCI produced a decrease in mean arterial pressure of 17 ± 3 mmHg (p < 0.001) and left ventricular contractility (end-systolic elastance) of 0.7 ± 0.1 mmHg/µL (p < 0.001).
2
Our novel SCI model produced signiﬁcant decreases in cardiac and hemodynamic function while preserving 33 ± 9% of white matter at the injury epicenter, which we believe makes it a useful pre-clinical model of SCI to study rehabilitation approaches designed to induce neuroplasticity.
3
The density of 5-HT+ ﬁbres caudal to the epicenter was reduced to 9 ± 2% of rostral density (Figure 6).

Research Summary

We have developed a novel moderately severe high-thoracic midline contusion SCI model that produces robust and clinically relevant impairment in cardiac and hemodynamic function whilst preserving 33 ± 9% of white matter at the injury epicenter. As such we believe this model provides a nice balance between producing a clinically relevant decline in CV function yet sparing sufﬁcient bulbo-spinal sympathetic and serotonergic pathways that can be targeted with therapies designed to induce/alter spinal neuroplasticity with a view to improving CV function. Here, we have presented a high-thoracic contusion model of SCI which demonstrated marked CV decline and modest tissue sparing at the epicenter, a feat not achieved by previous SCI models.

Practical Implications

Pre-clinical Model

The model is a useful pre-clinical model of SCI to study rehabilitation approaches designed to induce neuroplasticity.

Cardiovascular Decline

The model induces a clinically relevant decline in CV function, mimicking that which occurs clinically.

Animal Welfare

Animal health was greatly improved, and the model improves upon animal welfare and decreases the burden of care on researchers.

Study Limitations

1
This model has yet to be tested in female rats to account for sex differences in autonomic function.
2
the time course of CV function beyond 12 weeks in contusive models of SCI has not yet been characterized.
3
Although we know that cardiac dysfunction manifests within the ﬁrst 4 h post-SCI [31], and there are similar impairments at 3 and 7 days [53], 5 weeks [34], and 12 weeks post-SCI [32] the time course of CV function beyond 12 weeks in contusive models of SCI has not yet been characterized.

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