Infusion IV continue est le traitement de choix pour la route Arginine-vasopressine Receptor Blocker Conivaptan chez des souris pour étudier des maladies évoqués Oedème cérébral
Summary
Our studies have revealed that the beneficial effects of conivaptan are dependent on the method of delivery after experimental stroke in mice. We have developed a research protocol for delivery of the receptor blocker via IV catheter on stroke-evoked brain edema formation in mice.
Abstract
Accident vasculaire cérébral est l'une des principales causes de morbidité et de mortalité dans le monde. Stroke est compliquée par un œdème cérébral et d'autres événements physiopathologiques. Parmi les joueurs les plus importants dans le développement et l'évolution des accidents vasculaires cérébraux évoqués oedème cérébral est l'hormone arginine-vasopressine et ses récepteurs, V1a et V2. Récemment, le bloqueur des récepteurs conivaptan V1a et V2 a été d'attirer l'attention en tant que médicament potentiel pour réduire l'oedème cérébral après un AVC. Cependant, les modèles animaux qui impliquent des applications conivaptan dans la recherche de course doivent être modifiés en fonction des itinéraires possibles de l'administration. Voici les résultats de 48 h intraveineuse continue (IV) sont comparés avec les traitements intrapéritonéale (IP) de conivaptan après un AVC expérimental chez la souris. Nous avons développé un protocole dans lequel l'occlusion de l'artère cérébrale moyenne a été combinée avec l'installation du cathéter dans la veine jugulaire pour le traitement IV de conivaptan (0,2 mg) ou d'un véhicule. Différentes générations d'animaux ont été traités avec 0,2bol mg de conivaptan ou un véhicule IP par jour. Experimental œdème cérébral AVC évoquée a été évaluée chez des souris après IV continue et traitements IP. La comparaison des résultats a révélé que l'administration IV continue de conivaptan pallie post-ischémique œdème cérébral chez les souris, à la différence de l'administration IP de conivaptan. Nous concluons que notre modèle peut être utilisé pour des études futures applications conivaptan dans le contexte de l'AVC et l'oedème cérébral.
Introduction
Stroke continues to be an enormous burden for patients and clinicians. Animal stroke models have been used in the laboratory setting for nearly two decades.1 Nevertheless, experimental treatments that work in animals often fail in humans.2 This discrepancy in treatment outcomes may be due to various factors, such as administration routes for drugs used in animal research, drug metabolism and elimination rate, and many other aspects. One of the major complications of stroke, brain edema, is a focus of current research in neuroscience. Mechanisms of brain edema formation involve disturbances in water and electrolyte balance triggered by the arginine-vasopressin (AVP) response to ischemic brain injury.3 Therefore, AVP and its receptors (V1a and V2) are a major focus of research studies of post-ischemic brain edema formation.3
We have developed a methodology to study the effects of mixed arginine-vasopressin (V1a and V2) receptor blocker conivaptan on post-ischemic brain edema in mice.4 Molecular targets of conivaptan5 make the drug a suitable candidate for exploration of its properties in alleviation of brain edema. Furthermore, conivaptan needs to be studied in the context of pathophysiological events of stroke.6 In designing this study, we considered comparing treatment outcomes using two different routes of administration for conivaptan: intravenous (IV)4 and intraperitoneal (IP).7 Effects of the treatments on stroke-induced brain edema were evaluated. Here detailed protocols are described for surgical induction of experimental stroke by middle cerebral artery occlusion (MCAO), and followed by continuous conivaptan treatment using the installation of a jugular IV catheter. After induction of stroke, animals were randomly allocated into the following groups: vehicle or conivaptan (0.2 mg/day) treated IV or IP.
Protocol
Representative Results
Discussion
Cette étude a une valeur importante pour la recherche de la course préclinique. Cette étude révèle que continue perfusion IV de conivaptan (0,2 mg / jour) après un AVC expérimental chez la souris réduit efficacement l'œdème cérébral après 48 heures de traitement. L'effet de l'injection IP de la même dose de conivaptan sur l'oedème cérébral a également été étudiée. traitement Conivaptan par les deux voies IV et IP produit aquaresis chez la souris comme indiqué par: 1) augmentation d…
Disclosures
The authors have nothing to disclose.
Acknowledgements
Nous remercions Swedish Medical Center pour fournir le financement et les installations. Nous remercions également Craig Hospital pour l'utilisation généreuse de l'espace de laboratoire.
Materials
| Heated Pad | K&H Manufacturing Inc | 1060 | |
| Temperature Monitor with Rectal Probe | Physitemp | 7029 | |
| Silk Suture Spool, 6-0 | Surgical Specialties Corporation | SP114 | |
| Silk Suture on a Needle, 3-0 | Ethicon | 1684G | |
| Nylon Suture, 7-0 | Ethicon | 1696G | |
| Dental Resin Polysiloxane with Hardener | Heraeus Kulzer | 65817930 | |
| Microinfusion IV Pump | Kent Scietific | GT0897 | |
| Swivel 22GA | Instech | 375/22PS | |
| Laboratory Tubing, 0.94 x 0.51 mm | Dow Corning | 508-002 | |
| Laboratory Tubing, 3.18 x 1.98 mm | Dow Corning | 508-009 |
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