Name: continuous iv infusion is the choice treatment route for arginine-vasopressin receptor blocker conivaptan in mice to study stroke-evoked brain edema
Uploaded: 2016-09-01T14:00:00
Description: 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

我们感谢瑞典医疗中心提供资金和设施。我们也感谢克雷格医院的大量使用的实验室空间。

实验是按照美国国立卫生研究院的照顾和使用动物研究的指导方针进行，由瑞典医学中心的动物护理和使用委员会批准。所有的程序都用适当的无菌技术进行的。这项研究使用的实验动物均为男性，3个月大，体重野生型C57小鼠25日至27克 1. 在体内诱导中风<ol><li>预涂层与树脂牙灯丝此前的手术。 <ol><li>剪切从7-0尼龙线12毫米长片丝。混合2份该树脂与硬化剂的1份，然后?...

<ol>
	<li>Gueniau, C., Oberlander, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+kappa+opioid+agonist+niravoline+decreases+brain+edema+in+the+mouse+middle+cerebral+artery+occlusion+model+of+stroke.">The kappa opioid agonist niravoline decreases brain edema in the mouse middle cerebral artery occlusion model of stroke.</a> J Pharmacol Exp Ther. 282, 1-6 (1997).</li><li>Krafft, P. 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. P., 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=Arginine-vasopressin+V1+but+not+V2+receptor+antagonism+modulates+infarct+volume,+brain+water+content,+and+aquaporin-4+expression+following+experimental+stroke.">Arginine-vasopressin V1 but not V2 receptor antagonism modulates infarct volume, brain water content, and aquaporin-4 expression following experimental stroke.</a> Neurocrit Care. 12, 124-131 (2010).</li><li>Wallace, B. K., Jelks, K. A., O'Donnell, M. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ischemia-induced+stimulation+of+cerebral+microvascular+endothelial+cell+Na-K-Cl+cotransport+involves+p38+and+JNK+MAP+kinases.">Ischemia-induced stimulation of cerebral microvascular endothelial cell Na-K-Cl cotransport involves p38 and JNK MAP kinases.</a> Am J Physiol Cell Physiol. 302, C505-C517 (2012).</li><li>O'Donnell, M. 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=Intravenous+HOE-642+reduces+brain+edema+and+Na+uptake+in+the+rat+permanent+middle+cerebral+artery+occlusion+model+of+stroke:+evidence+for+participation+of+the+blood-brain+barrier+Na/H+exchanger.">Intravenous HOE-642 reduces brain edema and Na uptake in the rat permanent middle cerebral artery occlusion model of stroke: evidence for participation of the blood-brain barrier Na/H exchanger.</a> J Cereb Blood Flow Metab. 33, 225-234 (2013).</li><li>Walcott, B. P., Kahle, K. T., Simard, J. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Novel+treatment+targets+for+cerebral+edema.">Novel treatment targets for cerebral edema.</a> Neurotherapeutics. 9, 65-72 (2012).</li><li>Shen, Z., 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=Inhibition+of+G+protein-coupled+receptor+81+(GPR81)+protects+against+ischemic+brain+injury.">Inhibition of G protein-coupled receptor 81 (GPR81) protects against ischemic brain injury.</a> CNS Neurosci Ther. 21, 271-279 (2015).</li></ol>

这项研究有临床前研究中风重要的价值。这项研究表明，小鼠实验中风后考尼伐坦（0.2毫克/天）的持续静脉注射，有效降低治疗后的48小时脑水肿。 IP注射相同剂量对脑水肿考尼伐坦的效果也进行了研究。考尼伐坦治疗由双方IV和IP路由产生aquaresis由所示小鼠：1）血浆渗透压略高于生理水平的提高;和2）在尿渗透压降低由于在肾水再吸收的堵塞。因此，基于对治疗结果，我们报告中指出，四交付方...

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.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
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		<tr>
			<td>Heated Pad</td>
			<td>K&#38;H Manufacturing Inc</td>
			<td>1060</td>
			<td></td>
		</tr>
		<tr>
			<td>Temperature Monitor with Rectal Probe</td>
			<td>Physitemp</td>
			<td>7029</td>
			<td></td>
		</tr>
		<tr>
			<td>Silk Suture Spool, 6-0</td>
			<td>Surgical Specialties Corporation</td>
			<td>SP114</td>
			<td></td>
		</tr>
		<tr>
			<td>Silk Suture on a Needle, 3-0</td>
			<td>Ethicon</td>
			<td>1684G</td>
			<td></td>
		</tr>
		<tr>
			<td>Nylon Suture, 7-0</td>
			<td>Ethicon</td>
			<td>1696G</td>
			<td></td>
		</tr>
		<tr>
			<td>Dental Resin Polysiloxane with Hardener</td>
			<td>Heraeus Kulzer</td>
			<td>65817930</td>
			<td></td>
		</tr>
		<tr>
			<td>Microinfusion IV Pump</td>
			<td>Kent Scietific</td>
			<td>GT0897</td>
			<td></td>
		</tr>
		<tr>
			<td>Swivel 22GA</td>
			<td>Instech</td>
			<td>375/22PS</td>
			<td></td>
		</tr>
		<tr>
			<td>Laboratory Tubing, 0.94 x 0.51 mm</td>
			<td>Dow Corning</td>
			<td>508-002</td>
			<td></td>
		</tr>
		<tr>
			<td>Laboratory Tubing, 3.18 x 1.98 mm</td>
			<td>Dow Corning</td>
			<td>508-009</td>
			<td></td>
		</tr>
	</tbody>
</table>

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

中风是在世界发病和死亡的主要原因之一。中风是脑水肿等病理生理事件复杂化。间在中风诱发的脑水肿的发展和演变的最重要的球员是激素精氨酸加压素及其受体，V1a和V2。最近，V1a和V2受体阻滞剂考尼伐坦受到关注作为潜在的药物，以减少中风后的脑水肿。然而，这在中风研究涉及考尼伐坦应用动物模型需要根据给药可行途径进行修改。在这里，48小时连续静脉注射（IV）的结果与小鼠实验中风后腹腔内（IP）考尼伐坦治疗相比。我们开发了在大脑中动脉闭塞与导管安装组合为IV治疗考尼伐坦（0.2毫克）或车辆的颈静脉的协议。动物的不同队列，用0.2治疗考尼伐坦或车辆的IP毫克，每天丸。实验中风诱发脑水肿连续IV和IP处理后的小鼠进行了评估。的结果比较，可知考尼伐坦的连续IV施用减轻小鼠局部缺血后的脑水肿，与考尼伐坦的IP施用。我们得出结论，我们的模型，可用于在中风和脑水肿的上下文考尼伐坦应用今后的研究。

动物的体温是在生理范围内，并且在整个冲程感应的手术过程稳定。两个小鼠表现出NDS低于2 MCAO从该研究中排除之后。 在缺血小鼠48小时生产同侧半球梗死体积。的TTC染色切片的评价表明，半球的约50％是由缺血（ 图1D）后梗塞的影响，如通过Zeynalov，E。和多尔，S。，2009年10脑缺血性中风的发病引起严重?...

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.

持续静脉注射是精氨酸加压素受体拮抗剂考尼伐坦的选择治疗途径小鼠来研究中风诱发脑水肿

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 ...

Research

JoVE Journal

Medicine

Delivery of Therapeutic Agents Through Intracerebroventricular (ICV) and Intravenous (IV) Injection in Mice

Delivery of Therapeutic Agents Through Intracerebroventricular ICV and Intravenous IV Injection in Mice

交付的治疗药物通过侧脑室（ICV）和静脉（IV）注射液在小鼠

Despite the protective role that blood brain barrier plays in shielding the brain, it limits the access to the central nervous system (CNS) which most ...

科研

医学

The Measurement and Treatment of Suppression in Amblyopia

测量和制止在弱视治疗

Amblyopia, a developmental disorder of the visual cortex, is one of the leading causes of visual dysfunction in the working age population. Current ...

Orthotopic Aortic Transplantation in Mice for the Study of Vascular Disease

原位主动脉瓣移植在小鼠血管疾病的研究

Vascular procedures involving anastomoses in the mouse are generally thought to be difficult and highly dependent on the skill of the individual surgeon. ...

A Novel High-resolution In vivo Imaging Technique to Study the Dynamic Response of Intracranial Structures to Tumor Growth and Therapeutics

A Novel High-resolution In vivo Imaging Technique to Study the Dynamic Response of Intracranial Structures to Tumor Growth and Therapeutics

一种新型的高分辨率<em&gt;在体内</em&gt;成像技术研究肿瘤生长及治疗颅内结构的动态响应

We have successfully integrated previously established Intracranial window (ICW) technology 1-4 with intravital 2-photon confocal microscopy to develop a ...

Using Continuous Data Tracking Technology to Study Exercise Adherence in Pulmonary Rehabilitation

使用连续数据跟踪技术在肺康复研究锻炼坚持性

Pulmonary rehabilitation (PR) is an important component in the management of respiratory diseases. The effectiveness of PR is dependent upon adherence to ...

High-throughput Flow Cytometry Cell-based Assay to Detect Antibodies to N-Methyl-D-aspartate Receptor or Dopamine-2 Receptor in Human Serum

高通量流式细胞仪检测细胞为基础的试验检测抗体，以N-甲基-D-天冬氨酸受体或多巴胺2受体在人血清

Over the recent years, antibodies against surface and conformational proteins involved in neurotransmission have been detected in autoimmune CNS diseases ...

Heterotopic Mucosal Engrafting Procedure for Direct Drug Delivery to the Brain in Mice

异位黏膜移植程序直接给药到小鼠的大脑

Delivery of therapeutics into the brain is impeded by the presence of the blood-brain barrier (BBB) which restricts the passage of polar and high ...

Slow-release Drug Delivery through Elvax 40W to the Rat Retina: Implications for the Treatment of Chronic Conditions

通过40W的Elvax缓释给药的大鼠视网膜：对慢性疾病的治疗

Diseases of the retina are difficult to treat as the retina lies deep within the eye. Invasive methods of drug delivery are often needed to treat these ...

Using Saccadometry with Deep Brain Stimulation to Study Normal and Pathological Brain Function

使用Saccadometry与深部脑刺激来研究正常和病理脑功能

The oculomotor system involves a large number of brain areas including parts of the basal ganglia, and various neurodegenerative diseases including ...

Neurodegeneration in an Animal Model of Chronic Amyloid-beta Oligomer Infusion Is Counteracted by Antibody Treatment Infused with Osmotic Pumps

神经变性慢性淀粉样蛋白-β低聚物输注的动物模型是由抗体治疗灌注抵消与渗透泵

Decline in hippocampal-dependent explicit memory (memory for facts and events) is one of the earliest clinical symptom of Alzheimer&#39;s disease (AD). It ...