Name: intranasal administration of cns therapeutics to awake mice
Uploaded: 2013-04-08T12:00:00
Description: Watch this Scientific Journal Video about Intranasal Administration of CNS Therapeutics to Awake Mice at JoVE.com

作者要感谢体制的健康伴侣动物护理和使用委员会在地区医院。

1。驯化处理鼻内给药清醒小鼠介绍必须适应小鼠在发病前鼻内给药2至4个星期为一个周期的处理。驯化的处理是很重要的，因为它有助于确保正确的身体姿势清醒的鼻腔药物输送的最大效益。此外，服药后，小鼠没有得到很好的适应这个过程可以有一个严重的焦虑反应。小鼠应花费约2-3天在每个九个步骤进展到下一步骤之前，根据动物的舒适操作。鼠标的应...

<ol>
	<li>Dhuria, S. V., Hanson, L. R., Frey, W. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intranasal+delivery+to+the+central+nervous+system:+mechanisms+and+experimental+considerations.">Intranasal delivery to the central nervous system: mechanisms and experimental considerations.</a> J. Pharm Sci. 99, 1654-1673 (2010).</li><li>Thorne, R. G., Pronk, G. J., Padmanabhan, V., Frey, W. 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J., 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=Intranasal+insulin+prevents+cognitive+decline,+cerebral+atrophy+and+white+matter+changes+in+murine+type+I+diabetic+encephalopathy.">Intranasal insulin prevents cognitive decline, cerebral atrophy and white matter changes in murine type I diabetic encephalopathy.</a> Brain. 131, 3311-3334 (2008).</li><li>Francis, G., 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=Intranasal+insulin+ameliorates+experimental+diabetic+neuropathy.">Intranasal insulin ameliorates experimental diabetic neuropathy.</a> Diabetes. 58, 934-945 (2009).</li><li>Marks, D. R., Tucker, K., Cavallin, M. A., Mast, T. G., Fadool, D. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Awake+intranasal+insulin+delivery+modifies+protein+complexes+and+alters+memory,+anxiety,+and+olfactory+behaviors.">Awake intranasal insulin delivery modifies protein complexes and alters memory, anxiety, and olfactory behaviors.</a> J. Neurosci. 29, 6734-6751 (2009).</li><li>Hanson, L., 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=Intranasal+delivery+of+deferoxamine+reduces+spatial+memory+loss+in+APP/PS1+mice.">Intranasal delivery of deferoxamine reduces spatial memory loss in APP/PS1 mice.</a> Drug Delivery and Translational Research. 2, 160-168 (2012).</li><li>Danielyan, L., 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=Protective+effects+of+intranasal+losartan+in+the+APP/PS1+transgenic+mouse+model+of+Alzheimer+disease.">Protective effects of intranasal losartan in the APP/PS1 transgenic mouse model of Alzheimer disease.</a> Rejuvenation Research. 13, 195-201 (2010).</li><li>Fine, J. M., 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=Intranasal+deferoxamine+improves+performance+in+radial+arm+water+maze,+stabilizes+HIF-1alpha,+and+phosphorylates+GSK3beta+in+P301L+tau+transgenic+mice.">Intranasal deferoxamine improves performance in radial arm water maze, stabilizes HIF-1alpha, and phosphorylates GSK3beta in P301L tau transgenic mice.</a> Exp. Brain Res. 219, 381-390 (2012).</li><li>Lochhead, J. J., Thorne, R. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intranasal+delivery+of+biologics+to+the+central+nervous+system.">Intranasal delivery of biologics to the central nervous system.</a> Adv. Drug Deliv. Rev. 64 (11), 614-628 (2012).</li><li>Hanson, L. 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此方法显示如何小鼠可以给出针对脑无麻醉使用的常规剂量的滴鼻药。滴鼻药可以提供给大组小鼠长时间以最小的努力。一个组的20只小鼠可以鼻内视为由一个人在小于一小时。了大量的分子，包括小铁螯合剂间充质干细胞的生长因子，已被证明能够迅速针对CNS，并已显示出在啮齿类动物模型的疗效。建议直接交付机制，从鼻子到大脑外运输以及嗅觉和三叉神经和散流在血管周围的空间1,10。</...

<table border="1">
 <tbody>
 <tr>
 <td>Materials</td>
 <td>Company</td>
 <td>Cat #</td>
 <td>Comment</td>
 </tr>
 <tr>
 <td>P20 pipettor set at 6 &mu;l</td>
 <td></td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Gel loading pipette tips</td>
 <td></td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Timer</td>
 <td></td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Waste receptacle for tips</td>
 <td></td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Dosing sheet for notes</td>
 <td></td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Pen</td>
 <td></td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Drug and vehicle</td>
 <td></td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Container to hold drug vials</td>
 <td></td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Animals to be dosed</td>
 <td></td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Spare gloves</td>
 <td></td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Paper towels to wipe urine</td>
 <td></td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td></td>
 <td></td>
 <td></td>
 <td>Table 3. Materials Needed</td>
 </tr>
 </tbody>
</table>

intranasal administration of cns therapeutics to awake mice

鼻内给药是一种方法，治疗剂传递到中枢神经系统（CNS）。它是非侵入性的，不穿越血脑屏障进入中枢神经系统的允许大型分子。药物直接针对鼻腔给药的中枢神经系统，减少系统性风险，并因而不需要的全身性的副作用1。从鼻子到交货的中枢神经系统一起发生在几分钟之内的嗅觉和三叉神经通路通过细胞外的路线和，不需要药物绑定到任何受体或轴突运输2。鼻腔给药是一个广泛宣传的方法和目前正在使用的人体临床试验，3。 药物在动物模型中允许鼻腔给药的药代动力学分布性和有效性的初步评估。与小鼠，它是可能的管理定期使用斯佩恰清醒（非麻醉）的动物的药物汉化鼻内抓地力。清醒交付是有益的，因为它允许长期慢性无需麻醉剂量，花费较少的时间比麻醉，很多人可以学习和做的，所以，团队，技术人员可以剂量的小鼠在短期内大量。以这种方式给小鼠鼻内给药的治疗效能已被证明在一些包括胰岛素在糖尿病小鼠模型4-6和去铁胺在阿尔茨海默氏症小鼠模型的研究。7,8 小鼠鼻腔的抓地力可以学习的，但是是不容易的，需要实践，技巧和精确的抓地力，有效的药物输送到大脑和避免对肺，胃引流。抑制小鼠用手举行的颈部与地板平行，而药物传递用移液器使用优势手使用的改性在非优势手的浮渣。它通常需要3-4周的驯化处理前小鼠可以保持这种握法无应激反应。我们准备了这份朱庇特的视频，，鼻腔给药技术使这更容易。

有几种方法，以确定疗效的药物输送。首先是要管理的染料，如印度墨水或亚甲基蓝和鼻内的嗅觉上皮细胞内的动物实施安乐死后和后大脑被移除时，通过筛板进入中枢神经系统的可视化的染料。第二是要测量的药物交付通过使用放射性标记的标记，或使用未标记的分子的ELISA检测。 Hanson 等人分布在中枢神经系统用药后药物清醒小鼠中可以找到一个很好的例子。2012年7。我?...

Watch this Scientific Journal Video about Intranasal Administration of CNS Therapeutics to Awake Mice at JoVE.com

Intranasal Administration of CNS Therapeutics to Awake Mice

目的针对脑清醒小鼠鼻内给药的方法，进行说明。这种方法允许重复给药，长期使用鼻腔给药的药物无需麻醉，并以最小的全身暴露的鼻子到大脑传递。

清醒小鼠滴鼻的CNS药物治疗管理

Intranasal administration is a method of delivering  therapeutic agents to the central nervous system (CNS). It is  non-invasive and allows large ...

Research

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Intranasal administration has been reported to be a potential pathway for nose-to-brain delivery of therapeutic agents that circumvents the blood-brain ...