Rapamycin Exacerbates Cardiovascular Dysfunction after Complete High-Thoracic Spinal Cord Injury

JOURNAL OF NEUROTRAUMA, 2018 · DOI: 10.1089/neu.2017.5184 · Published: March 15, 2018

Spinal Cord Injury Pharmacology Neurology

Simple Explanation

This study investigates the effects of rapamycin (RAP) on cardiovascular function after spinal cord injury (SCI). The researchers aimed to see if RAP could reduce autonomic dysreflexia (AD), a dangerous condition characterized by high blood pressure, by affecting plasticity in the spinal cord. Rats with SCI were treated with RAP, and their blood pressure and heart rate were monitored. The results indicated that RAP worsened cardiovascular issues after SCI, causing elevated resting blood pressure and increased frequency of spontaneous AD. These findings suggest that RAP is not a suitable therapeutic intervention for SCI as it exacerbates cardiovascular dysfunction, possibly due to increased peripheral nociceptor sensitivity or vascular resistance.

Study Duration

4 weeks

Participants

33 rats (naive and SCI)

Evidence Level

Not specified

Key Findings

1
Rapamycin significantly elevated resting blood pressure in rats with SCI, with average daily blood pressure rising above even normal naïve levels within one week after injury.
2
Rapamycin significantly increased the frequency of daily spontaneous autonomic dysreflexia (sAD) and increased the absolute blood pressure induced by colorectal distension (CRD) at three weeks post-injury.
3
These cardiovascular effects were not correlated with changes in the density of nociceptive c-fibers or c-Fos+ neurons, suggesting that intraspinal plasticity associated with AD was not altered by the treatment.

Research Summary

The study aimed to determine if rapamycin (RAP) could modulate autonomic dysreflexia (AD) development after spinal cord injury (SCI) by impeding intraspinal plasticity. RAP was administered to naïve and injured rats, and hemodynamic monitoring was conducted. Results showed that RAP significantly exacerbated body weight loss and caused a marked elevation in resting blood pressure after SCI. It also increased the frequency of spontaneous AD and the absolute blood pressure induced by colorectal distension. The findings caution against the use of RAP as a therapeutic intervention for SCI because it evokes toxic weight loss and exacerbates cardiovascular dysfunction, possibly mediated by increased peripheral nociceptor sensitivity and/or vascular resistance.

Practical Implications

Caution in Therapeutic Use

The study suggests caution in using rapamycin as a therapeutic intervention for SCI due to its adverse cardiovascular effects.

Alternative Mechanisms

The study indicates that rapamycin's cardiovascular effects are likely mediated by mechanisms other than intraspinal plasticity, such as increased peripheral nociceptor sensitivity or vascular resistance.

Further Research Needed

Further research is needed to understand the specific central and/or peripheral mechanisms by which rapamycin exacerbates cardiovascular dysfunction after SCI.

Study Limitations

1
The specific central and/or peripheral mechanisms underlying rapamycin's effects were not identified.
2
The study had a 30% attrition rate in the SCI + RAP group.
3
The effects of a single administration of RAP at a clinically relevant time point were not investigated.

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