Continua infusione endovenosa è la Strada del trattamento scelta per arginina-vasopressina bloccante dei recettori conivaptan nei topi per studiare Stroke-evocato Cervello Edema
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
L'ictus è una delle principali cause di morbilità e mortalità nel mondo. Ictus è complicata da edema cerebrale e altri eventi fisiopatologici. Tra i giocatori più importanti per lo sviluppo e l'evoluzione di edema cerebrale ictus-evocato è l'ormone arginina-vasopressina e dei suoi recettori, V1a e V2. Recentemente, il bloccante dei recettori conivaptan V1a e V2 ha continuato ad attrarre l'attenzione come un potenziale farmaco per ridurre l'edema cerebrale dopo ictus. Tuttavia, i modelli animali che coinvolgono applicazioni conivaptan nella ricerca corsa devono essere modificati sulla base di percorsi praticabili di somministrazione. Ecco i risultati di 48 ore endovenosa continua (IV) sono confrontati con i trattamenti intraperitoneale (IP) conivaptan dopo l'ictus sperimentale nei topi. Abbiamo sviluppato un protocollo in cui occlusione dell'arteria cerebrale media è stato combinato con l'installazione del catetere nella vena giugulare per il trattamento IV di conivaptan (0,2 mg) o veicolo. Diverse coorti di animali sono stati trattati con 0,2mg in bolo di conivaptan o di un veicolo IP quotidiana. Sperimentale ictus-evocato edema cerebrale è stata valutata in topi dopo IV continuo e trattamenti IP. Il confronto dei risultati è emerso che la somministrazione IV continua di conivaptan allevia post-ischemica edema cerebrale nei topi, a differenza della somministrazione IP di conivaptan. Concludiamo che il nostro modello può essere utilizzato per i futuri studi di applicazioni conivaptan nel contesto di ictus e di edema cerebrale.
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
Questo studio ha un valore importante per la ricerca preclinica ictus. Questo studio rivela che continua infusione endovenosa di conivaptan (0,2 mg / die) dopo ictus sperimentale nei topi riduce efficacemente l'edema cerebrale dopo 48 ore di trattamento. L'effetto di iniezione IP la stessa dose di conivaptan su edema cerebrale è stato anche indagato. trattamento conivaptan da entrambe le vie IV e IP produce acquaresi nei topi, come indicato da: 1) aumento della osmolalità plasmatica leggermente al di sopra i l…
Declarações
The authors have nothing to disclose.
Acknowledgements
Ringraziamo Swedish Medical Center per fornire il finanziamento e strutture. Ringraziamo anche Craig Hospital per l'uso generoso di spazio di laboratorio.
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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