Kontinuierliche intravenöse Infusion ist die Wahl Behandlung Weg für Arginin-Vasopressin-Rezeptorblocker Conivaptan bei Mäusen Stroke-evozierte Hirnödem zu studieren
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
Schlaganfall ist eine der Hauptursachen von Morbidität und Mortalität in der Welt. Schlaganfall wird durch Hirnödem und anderen pathophysiologischen Ereignisse kompliziert. Zu den wichtigsten Akteure in der Entwicklung und Evolution von Schlaganfall-evozierte Hirnödem ist das Hormon Arginin-Vasopressin und seine Rezeptoren, V1a und V2. Vor kurzem hat die V1a und V2-Rezeptorblockers Conivaptan Aufmerksamkeit als potentielle Arzneimittelangezogen Hirnödem nach Schlaganfall zu reduzieren. Allerdings Tiermodelle, die conivaptan Anwendungen in der Schlaganfallforschung einbeziehen müssen basierend auf machbar Verabreichungswege geändert werden. Hier werden die Ergebnisse des 48 Stunden kontinuierlicher intravenöser (IV) sind gegenüber intraperitoneal (IP) Conivaptan Behandlungen nach experimentellem Schlaganfall in Mäusen. Wir entwickelten ein Protokoll, in dem mittleren zerebralen Arterienverschluss mit Katheter Einbau in die Jugularvene zur intravenösen Behandlung von Conivaptan (0,2 mg) oder Vehikel kombiniert wurde. Verschiedene Kohorten von Tieren wurden mit 0,2 behandeltmg-Bolus von conivaptan oder Fahrzeug IP täglich. Experimentelle Schlaganfall-evozierte Hirnödem wurde bei Mäusen nach einer kontinuierlichen IV und IP-Behandlungen ausgewertet. Vergleich der Ergebnisse zeigte, dass die kontinuierliche Verabreichung von IV Conivaptan mildert post-ischämische Hirnödem in Mäusen, im Gegensatz zu der IP-Verabreichung von Conivaptan. Wir schließen daraus, dass unser Modell für zukünftige Studien von Conivaptan Anwendungen im Zusammenhang mit Schlaganfall und Hirnödem verwendet werden kann.
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
Diese Studie hat wichtige Wert für die präklinische Schlaganfallforschung. Diese Studie zeigt, dass eine kontinuierliche intravenöse Infusion von conivaptan (0,2 mg / Tag) nach experimentellem Schlaganfall bei Mäusen effizient Hirnödem nach 48 Stunden der Behandlung reduziert. Die Wirkung der IP-Injektion der gleichen Dosis von Conivaptan auf Hirnödem wurde ebenfalls untersucht. Conivaptan Behandlung sowohl von IV und IP-Routen erzeugt aquaresis in Mäusen, wie durch: 1) Erhöhung der Plasma Osmolalität leicht ü…
Disclosures
The authors have nothing to disclose.
Acknowledgements
Wir danken Swedish Medical Center für die Finanzierung und Einrichtungen. Wir danken auch Craig-Krankenhaus für die großzügige Verwendung von Laborfläche.
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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