Minocycline Partially Restores Blood Pressure Regulation After Experimental Spinal Cord Injury
Notice bibliographique
Résumé
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.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».