Name: continuous iv infusion is the choice treatment route for arginine-vasopressin receptor blocker conivaptan in mice to study stroke-evoked brain edema
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Vi tackar svenska Medical Center för att tillhandahålla finansiering och faciliteter. Vi tackar även Craig Hospital för den generösa användningen av laboratorielokaler.

Experiment utfördes i enlighet med riktlinjerna i National Institutes of Health för skötsel och användning av djur i forskning och godkändes av Svenska Medical Center Animal Care och användning kommittén. Alla förfaranden genomfördes med lämpliga aseptiska tekniker. Försöksdjur som används för studien var män, 3 månader gammal, vild typ C57 möss med kroppsvikt 25-27 g. 1. In vivo Stroke Induktion <ol><li> Pre-belägga Filament med Dental Resin före det kirurgiska...

<ol>
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R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Etiology+of+stroke+and+choice+of+models.">Etiology of stroke and choice of models.</a> Int J Stroke. 7, 398-406 (2012).</li><li>Vakili, A., Kataoka, H., Plesnila, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Role+of+arginine+vasopressin+V1+and+V2+receptors+for+brain+damage+after+transient+focal+cerebral+ischemia.">Role of arginine vasopressin V1 and V2 receptors for brain damage after transient focal cerebral ischemia.</a> J Cereb Blood Flow Metab. 25, 1012-1019 (2005).</li><li>Zeynalov, E., Jones, S. M., Seo, J. W., Snell, L. D., Elliott, J. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Arginine-Vasopressin+Receptor+Blocker+Conivaptan+Reduces+Brain+Edema+and+Blood-Brain+Barrier+Disruption+after+Experimental+Stroke+in+Mice.">Arginine-Vasopressin Receptor Blocker Conivaptan Reduces Brain Edema and Blood-Brain Barrier Disruption after Experimental Stroke in Mice.</a> PloS one. 10, e0136121 (2015).</li><li>Med Lett Drugs Ther.. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Conivaptan+(Vaprisol)+for+hyponatremia.">Conivaptan (Vaprisol) for hyponatremia.</a> The Medical letter on drugs and therapeutics. 48, 51-52 (2006).</li><li>Zhao, X. Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+of+arginine+vasopressin+on+the+cortex+edema+in+the+ischemic+stroke+of+Mongolian+gerbils.">Effect of arginine vasopressin on the cortex edema in the ischemic stroke of Mongolian gerbils.</a> Neuropeptides. 51, 55-62 (2015).</li><li>Manaenko, A., Chen, H., Kammer, J., Zhang, J. H., Tang, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparison+Evans+Blue+injection+routes:+Intravenous+versus+intraperitoneal,+for+measurement+of+blood-brain+barrier+in+a+mice+hemorrhage+model.">Comparison Evans Blue injection routes: Intravenous versus intraperitoneal, for measurement of blood-brain barrier in a mice hemorrhage model.</a> J Neurosci Methods. 195, 206-210 (2011).</li><li>Adams, S., Pacharinsak, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mouse+anesthesia+and+analgesia.">Mouse anesthesia and analgesia.</a> Curr Protoc Mouse Biol. 5, 51-63 (2015).</li><li>Zeynalov, E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+perivascular+pool+of+aquaporin-4+mediates+the+effect+of+osmotherapy+in+postischemic+cerebral+edema.">The perivascular pool of aquaporin-4 mediates the effect of osmotherapy in postischemic cerebral edema.</a> Crit Care Med. 36, 2634-2640 (2008).</li><li>Zeynalov, E., Dore, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Low+doses+of+carbon+monoxide+protect+against+experimental+focal+brain+ischemia.">Low doses of carbon monoxide protect against experimental focal brain ischemia.</a> Neurotox Res. 15, 133-137 (2009).</li><li>Zeynalov, E., Nemoto, M., Hurn, P. D., Koehler, R. C., Bhardwaj, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neuroprotective+effect+of+selective+kappa+opioid+receptor+agonist+is+gender+specific+and+linked+to+reduced+neuronal+nitric+oxide.">Neuroprotective effect of selective kappa opioid receptor agonist is gender specific and linked to reduced neuronal nitric oxide.</a> J Cereb Blood Flow Metab. 26, 414-420 (2006).</li><li>Ma, M. C., Qian, H., Ghassemi, F., Zhao, P., Xia, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Oxygen-sensitive+{delta}-opioid+receptor-regulated+survival+and+death+signals:+novel+insights+into+neuronal+preconditioning+and+protection.">Oxygen-sensitive {delta}-opioid receptor-regulated survival and death signals: novel insights into neuronal preconditioning and protection.</a> J Biol Chem. 280, 16208-16218 (2005).</li><li>Ahmad, M., Zhang, Y., Liu, H., Rose, M. E., Graham, S. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prolonged+opportunity+for+neuroprotection+in+experimental+stroke+with+selective+blockade+of+cyclooxygenase-2+activity.">Prolonged opportunity for neuroprotection in experimental stroke with selective blockade of cyclooxygenase-2 activity.</a> Brain Res. 1279, 168-173 (2009).</li><li>Meisel, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Preventive+antibacterial+treatment+improves+the+general+medical+and+neurological+outcome+in+a+mouse+model+of+stroke.">Preventive antibacterial treatment improves the general medical and neurological outcome in a mouse model of stroke.</a> Stroke. 35, 2-6 (2004).</li><li>Miner, N. A., Koehler, J., Greenaway, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intraperitoneal+injection+of+mice.">Intraperitoneal injection of mice.</a> Appl Microbiol. 17, 250-251 (1969).</li><li>Adis International Limited. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Conivaptan:+YM+087.">Conivaptan: YM 087.</a> Drugs in R&amp;D. 5, 94-97 (2004).</li><li>Murphy, T., Dhar, R., Diringer, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Conivaptan+bolus+dosing+for+the+correction+of+hyponatremia+in+the+neurointensive+care+unit.">Conivaptan bolus dosing for the correction of hyponatremia in the neurointensive care unit.</a> Neurocrit Care. 11, 14-19 (2009).</li><li>Liu, X., Nakayama, S., Amiry-Moghaddam, M., Ottersen, O. 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Denna studie har viktiga värde för preklinisk strokeforskning. Denna studie visar att kontinuerlig intravenös infusion av conivaptan (0,2 mg / dag) efter experimentell stroke hos möss minskar effektivt hjärnödem efter 48 timmar av behandling. Effekten av IP-injektion av samma dos av conivaptan på hjärnödem undersöktes också. Conivaptan behandling av både IV och IP-vägar ger aquares hos möss som indikeras av: 1) ökning av plasmaosmolalitet något över fysiologiska nivåer; och 2) minskning i urin osmolali...

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.

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continuous iv infusion is the choice treatment route for arginine-vasopressin receptor blocker conivaptan in mice to study stroke-evoked brain edema

Stroke är en av de främsta orsakerna till sjuklighet och dödlighet i världen. Stroke kompliceras av hjärnödem och andra patofysiologiska händelser. Bland de viktigaste aktörerna i utvecklingen och utvecklingen av stroke-framkallade hjärnödem är hormonet arginin-vasopressin och dess receptorer, V1a och V2. På senare tid har V1a och V2 receptorblockeraren conivaptan dragit till sig uppmärksamhet som ett potentiellt läkemedel för att minska hjärnödem efter stroke. Men djurmodeller som innebär conivaptan applikationer i stroke behöver ändras baserat på möjliga administreringssätt. Här resultaten av 48 timmar kontinuerlig intravenös (IV) jämförs med intraperitoneal (IP) conivaptan behandlingar efter experimentell stroke hos möss. Vi utvecklat ett protokoll där arteria cerebri media ocklusion kombinerades med kateterinstallation i jugularvenen för IV behandling av conivaptan (0,2 mg) eller vehikel. Olika grupper av djur behandlades med 0,2mg bolusdos av conivaptan eller fordon IP dagligen. Experimentell stroke-framkallade hjärnödem utvärderades i möss efter kontinuerlig IV och IP-behandlingar. Jämförelse av resultaten visade att den kontinuerliga iv administrering av conivaptan lindrar post-ischemisk hjärnödem hos möss, till skillnad från IP-administrering av conivaptan. Vi drar slutsatsen att vår modell kan användas för framtida studier av conivaptan tillämpningar i samband med stroke och hjärnödem.

Kroppstemperaturen hos djuren var inom det fysiologiska området och stabil under hela det kirurgiska förfarandet för stroke induktion. Två möss som uppvisade NDS lägre än 2 omedelbart efter MCAO uteslöts från studien. MCAO i möss producerar infarktvolymen i den ipsilaterala halvklotet på 48 timmar. Utvärdering av TTC-färgade skivor visar att omkring 50% av halvklotet påverkas av infarkt efter kortex (figu...

Watch this Scientific Journal Video about Continuous IV Infusion is the Choice Treatment Route for Arginine-vasopressin Receptor Blocker Conivaptan in Mice to Study Stroke-evoked Brain Edema at JoVE.c

Continuous IV Infusion is the Choice Treatment Route for Arginine-vasopressin Receptor Blocker Conivaptan in Mice to Study Stroke-evoked Brain Edema

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.

Kontinuerlig intravenös infusion är valet behandling Route för arginin-vasopressin-receptorblockerare Conivaptan i möss för att studera Stroke-framkallade hjärnödem

Stroke is one of the major causes of morbidity and mortality in the world. Stroke is complicated by brain edema and other pathophysiological events. Among ...

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