Continue IV Infusion is de keuze behandeling Route voor arginine-vasopressine Receptor Blocker conivaptan in Muizen op de studie-Stroke opgeroepen hersenoedeem
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
Beroerte is een van de belangrijkste oorzaken van morbiditeit en mortaliteit in de wereld. Stroke wordt bemoeilijkt door hersenoedeem en andere pathofysiologische gebeurtenissen. Een van de belangrijkste spelers in de ontwikkeling en evolutie van beroerte opgewekte hersenoedeem is het hormoon arginine-vasopressine en zijn receptoren, V1a en V2. Onlangs heeft de V1a en V2-receptor blokker conivaptan het aantrekken van de aandacht als een potentieel geneesmiddel voor hersenoedeem te verminderen na een beroerte. Echter diermodellen die conivaptan toepassingen de beroerte onderzoek moeten worden aangepast op basis van mogelijke toedieningswegen. Hier de resultaten van 48 uur continue intraveneuze (IV) vergeleken met intraperitoneale (IP) conivaptan behandelingen na experimentele beroerte bij muizen. We ontwikkelden een protocol waarin de middelste cerebrale slagader occlusie met catheter installatie werd gecombineerd in de halsader voor IV behandeling van conivaptan (0,2 mg) of voertuig. Verschillende cohorten dieren werden behandeld met 0,2mg bolus van conivaptan of voertuig IP per dag. Experimenteel-takt opgeroepen hersenoedeem werd geëvalueerd in muizen na continue IV en IP-behandelingen. Vergelijking van de resultaten bleek dat de continue intraveneuze toediening van conivaptan vermindert post-ischemische hersenoedeem bij muizen, in tegenstelling tot de IP toediening van conivaptan. Concluderen we dat ons model kan worden gebruikt voor toekomstige studies conivaptan toepassingen in de context van een beroerte en hersenoedeem.
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
Deze studie heeft belangrijke waarde voor preklinisch beroerte onderzoek. Deze studie toont aan dat continue IV infusie van conivaptan (0,2 mg / dag) na experimentele beroerte bij muizen vermindert efficiënt hersenoedeem na 48 uur behandeling. Het effect van IP injectie van dezelfde dosis conivaptan op hersenoedeem werd eveneens onderzocht. Conivaptan behandeling van zowel IV en IP routes produceert aquaresis bij muizen aangegeven: 1) verhoging van plasma osmolaliteit iets boven fysiologische niveaus; en 2) afname van …
Disclosures
The authors have nothing to disclose.
Acknowledgements
Wij danken Swedish Medical Center voor het verstrekken van de financiering en de faciliteiten. We danken ook Craig Hospital voor de royale gebruik van de laboratoriumruimte.
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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