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

Area of Science:

• Neuroscience
• Physiology
• Pharmacology

Background:

• Autonomic dysreflexia (AD) is a dangerous complication of spinal cord injury (SCI) above T6.
• Intraspinal plasticity is implicated in AD development.
• Mammalian target of rapamycin (mTOR) influences plasticity and nociception in SCI.

Purpose of the Study:

• To investigate if rapamycin (RAP) can impede intraspinal plasticity and modulate AD development post-SCI.
• To evaluate the effects of prolonged RAP treatment on AD frequency and severity in a rat SCI model.

Main Methods:

• Rats with T4 spinal transection received daily rapamycin (RAP) or vehicle for four weeks.
• Hemodynamic monitoring assessed spontaneous and colorectal distention (CRD)-induced AD.
• Evaluated body weight changes, resting blood pressure, and cardiovascular responses.

Main Results:

• RAP treatment exacerbated weight loss and elevated resting blood pressure post-SCI.
• RAP significantly increased the frequency of spontaneous AD and CRD-induced hypertension.
• No changes in nociceptive c-fiber density or c-Fos+ neurons were observed, suggesting plasticity was not altered.

Conclusions:

• Rapamycin exacerbates cardiovascular dysfunction and AD in SCI rats.
• RAP treatment is not recommended for SCI due to toxic weight loss and worsened AD.
• Potential mechanisms involve increased peripheral nociceptor sensitivity or vascular resistance.