Minocycline Partially Restores Blood Pressure Regulation After Experimental Spinal Cord Injury
Authors: Ruiz‐Romero Ian A , Squair Jordan , Gopaul Ray , Liu Jie , West Christopher R , Krassioukov Andrei V 
Published: November 2023

OBJECTIVE

Cardiovascular dysfunction, which manifests as chronic hypotension, autonomic dysreflexia, and orthostatic hypotension, is common after high‐level spinal cord injury (SCI), likely contributing to this population's dramatically increased odds for stroke and heart disease. The degree of dysfunction is thought to be less severe in those with a greater preservation of descending sympatho‐excitatory axons; hence, therapies targeting the preservation of these axons in the acute stages of SCI may improve cardiovascular function and reduce cardiovascular disease risk in people with SCI. Minocycline, a clinically available antibiotic with anti‐inflammatory properties, has demonstrated extremely promising neuroprotective effects through myelin preservation in a variety of animal models and improved motor recovery in a groundbreaking preliminary human trial. As such, the purpose of this study was to investigate the effect of minocycline on both the motor and cardiovascular systems in a well‐established animal model.

DESIGN/METHODS

32 Male Wistar rats were randomized to either a treatment group (minocycline; n=14) or a control group (vehicle; n=18), and were followed for 2 months post‐SCI. All rats received a T3 severe contusion (Infinite‐Horizons impactor, 400kdyn, 5s dwell time). Minocycline (or saline vehicle) was administered at 1 hour post‐injury (90mg/kg), then every twelve hours for two weeks (45mg/kg). Baseline hemodynamics and the severity of autonomic dysreflexia were assessed at 2 months post‐injury using an implantable telemetry blood pressure device (right carotid approach) under urethane anesthesia. Autonomic dysreflexia was induced by inserting a balloon‐tipped catheter in the rectum (i.e. colorectal distension). Baseline motor behaviour (Basso, Beattie, and Bresnahan [BBB] method) was also assessed pre‐SCI and every 7 days until study end‐point.

RESULTS

We show that the acute administration of minocycline significantly improves resting systolic blood pressure (107±1.5mmHg) compared to vehicle (98±2.2mmHg; p=0.034). Moreover, the severity of autonomic dysreflexia in response to colorectal distension was remarkably reduced by 33% in animals treated with minocycline (p=0.025). In contrast to the cardiovascular improvements, there were no differences in motor function (BBB score) between the minocycline and vehicle groups (all p>0.05).

CONCLUSIONS

We examined the effect of minocycline administration on cardiovascular function following SCI and provide the first evidence that this promising drug is able to improve baseline hemodynamics. Furthermore, the diminished severity of autonomic dysreflexia following treatment may indicate a more robust preservation of cardiovascular autonomic function compared to those without treatment. That we saw no concomitant improvement in motor function suggests that determining the independent impact of both existing and novel neuroprotective drugs on motor and cardiovascular function is critical.

Support or Funding Information

The lab of AV Krassioukov is supported by the Heart and Stroke Foundation of Canada, the Canadian Institutes of Health Research, and the Craig H. Neilsen Foundation. This project was supported by a SEED grant from the International Collaboration on Repair Discoveries.