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.
Slagtilfælde er en af de hyppigste årsager til sygelighed og dødelighed i verden. Slagtilfælde kompliceres af hjerneødem og andre patofysiologiske begivenheder. Blandt de vigtigste spillere i udvikling og videreudvikling af slagtilfælde-fremkaldte hjerneødem er det hormon arginin-vasopressin og dets receptorer, V1a og V2. For nylig har V1a og V2-receptor blocker conivaptan tiltrukket opmærksomhed som et potentielt lægemiddel til at reducere hjerneødem efter slagtilfælde. Men dyremodeller, som involverer conivaptan applikationer i slagtilfælde forskning skal ændres på grundlag af mulige administrationsveje,. Her resultaterne af 48 timers kontinuerlig intravenøs (IV) sammenlignes med intraperitoneal (IP) conivaptan behandlinger efter eksperimentel slagtilfælde hos mus. Vi udviklede en protokol, hvor mellem-cerebral arterieokklusion blev kombineret med kateter installation i halsvenen til intravenøs behandling af conivaptan (0,2 mg) eller vehikel. Forskellige kohorter af dyr blev behandlet med 0,2mg bolus af conivaptan eller køretøj IP dagligt. Eksperimentel slagtilfælde fremkaldte hjerneødem blev evalueret i mus efter kontinuerlig IV og IP-behandlinger. Sammenligning af resultaterne viste, at kontinuerlig intravenøs administration af conivaptan letter post-iskæmisk hjerneødem i mus, i modsætning til IP administration af conivaptan. Vi konkluderer, at vores model kan anvendes til fremtidige studier af conivaptan applikationer i forbindelse med slagtilfælde og hjerneødem.
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.
Denne undersøgelse har vigtig værdi for præklinisk slagtilfælde forskning. Denne undersøgelse viser, at kontinuerlig intravenøs infusion af conivaptan (0,2 mg / dag) efter eksperimentel slagtilfælde hos mus effektivt reducerer hjerneødem efter 48 timers behandling. Virkningen af IP-injektion af den samme dosis af conivaptan på hjerneødem blev også undersøgt. Conivaptan behandling af både IV og IP ruter producerer aquaresis i mus som angivet ved: 1) stigning i plasma osmolalitet lidt over fysiologiske …
The authors have nothing to disclose.
Vi takker Swedish Medical Center for at levere finansiering og faciliteter. Vi takker også Craig Hospital for den generøse brug af laboratorie plads.
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 |