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

लेखकों के लिए धन्यवाद HealthPartners संस्थागत पशु की देखभाल और क्षेत्र के अस्पताल में समिति का उपयोग करना चाहते हैं.

1. Intranasal Dosing के लिए जाग चूहे के लिए हैंडलिंग acclimation परिचय चूहे intranasal dosing के शुरू होने से पहले दो - चार सप्ताह की अवधि के लिए से निपटने के लिए इस्तेमाल किया जाना चाहिए. से निपटने के लिए acclimation महत्व?...

<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. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Delivery+of+insulin-like+growth+factor-I+to+the+rat+brain+and+spinal+cord+along+olfactory+and+trigeminal+pathways+following+intranasal+administration.">Delivery of insulin-like growth factor-I to the rat brain and spinal cord along olfactory and trigeminal pathways following intranasal administration.</a> Neuroscience. , 127-481 (2004).</li><li>Benedict, 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=Intranasal+insulin+as+a+therapeutic+option+in+the+treatment+of+cognitive+impairments.">Intranasal insulin as a therapeutic option in the treatment of cognitive impairments.</a> Exp. Gerontol. 46, 112-115 (2011).</li><li>Francis, G. 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. 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=Intranasal+deferoxamine+provides+increased+brain+exposure+and+significant+protection+in+rat+ischemic+stroke.">Intranasal deferoxamine provides increased brain exposure and significant protection in rat ischemic stroke.</a> J. Pharmacol. Exp Ther. 330, 679-686 (2009).</li><li>Reger, M. A., 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=Effects+of+intranasal+insulin+on+cognition+in+memory-impaired+older+adults:+modulation+by+APOE+genotype.">Effects of intranasal insulin on cognition in memory-impaired older adults: modulation by APOE genotype.</a> Neurobiol. Aging. 27, 451-458 (2006).</li><li>Kim, C. H., Song, H. y. u. n., M, E. u. n. A. h. n., Lee, Y., G, J., Yoon, J. H. <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+hypo-,+iso-+and+hypertonic+saline+irrigation+on+secretory+mucins+and+morphology+of+cultured+human+nasal+epithelial+cells.">Effect of hypo-, iso- and hypertonic saline irrigation on secretory mucins and morphology of cultured human nasal epithelial cells.</a> Acta Otolaryngol. 125, 1296-1300 (2005).</li><li>Greiff, L., Andersson, M., Wollmer, P., Persson, C. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hypertonic+saline+increases+secretory+and+exudative+responsiveness+of+human+nasal+airway+in+vivo.">Hypertonic saline increases secretory and exudative responsiveness of human nasal airway in vivo.</a> Eur. Respir. J. 21, 308-312 (2003).</li></ol>

इस विधि से पता चलता है कि किस तरह चूहों intranasal दवा के नियमित खुराक के लिए संज्ञाहरण के उपयोग के बिना मस्तिष्क को लक्ष्य बनाएं दिया जा सकता है. Intranasal दवा न्यूनतम प्रयास के साथ समय की विस्तारित अवधि के लिए चूहो...

<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

Intranasal administration is a method of delivering therapeutic agents to the central nervous system (CNS). It is non-invasive and allows large molecules that do not cross the blood-brain barrier access to the CNS. Drugs are directly targeted to the CNS with intranasal delivery, reducing systemic exposure and thus unwanted systemic side effects1. Delivery from the nose to the CNS occurs within minutes along both the olfactory and trigeminal neural pathways via an extracellular route and does not require drug to bind to any receptor or axonal transport2. Intranasal delivery is a widely publicized method and is currently being used in human clinical trials3.
Intranasal delivery of drugs in animal models allows for initial evaluation of pharmacokinetic distribution and efficacy. With mice, it is possible to administer drugs to awake (non-anesthetized) animals on a regular basis using a specialized intranasal grip. Awake delivery is beneficial because it allows for long-term chronic dosing without anesthesia, it takes less time than with anesthesia, and can be learned and done by many people so that teams of technicians can dose large numbers of mice in short periods. Efficacy of therapeutics administered intranasally in this way to mice has been demonstrated in a number of studies including insulin in diabetic mouse models 4-6 and deferoxamine in Alzheimer's mouse models. 7,8
The intranasal grip for mice can be learned, but is not easy and requires practice, skill, and a precise grip to effectively deliver drug to the brain and avoid drainage to the lung and stomach. Mice are restrained by hand using a modified scruff in the non-dominant hand with the neck held parallel to the floor, while drug is delivered with a pipettor using the dominant hand. It usually takes 3-4 weeks of acclimating to handling before mice can be held with this grip without a stress response. We have prepared this JoVE video to make this intranasal delivery technique more accessible.

दवा वितरण की प्रभावकारिता निर्धारित करने के लिए कई तरीके हैं. 1 intranasally भारत स्याही या methylene नीले रंग के रूप में इस तरह के एक डाई, प्रशासन और डाई कल्पना घ्राण उपकला के भीतर पशु की इच्छामृत्यु के बाद और मस्तिष्?...

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

Intranasally जाग मस्तिष्क को निशाना बनाने का उद्देश्य के लिए चूहों को दवा प्रशासन के लिए एक विधि का वर्णन है. इस विधि संज्ञाहरण के बिना दवा के intranasal प्रशासन का उपयोग करने से अधिक लंबी अवधि, वितरण और न्यूनतम प्रणालीगत जोखिम के साथ नाक मस्तिष्क dosing दोहराने के लिए अनुमति देता है.

CNS चिकित्सा intranasal जाग चूहे प्रशासन

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

Research

JoVE Journal

Medicine

Rat Model of Blood-brain Barrier Disruption to Allow Targeted Neurovascular Therapeutics

रक्त मस्तिष्क बाधा विघटन के चूहे मॉडल Neurovascular चिकित्सा लक्षित करने के लिए अनुमति दें

Endothelial cells with tight junctions along with the basement membrane and astrocyte end feet surround cerebral blood vessels to form the blood-brain ...

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

एक उपन्यास उच्च संकल्प<em&gt; विवो में</emट्यूमर के विकास और चिकित्सा विज्ञान के लिए Intracranial संरचनाएं के गतिशील प्रतिक्रिया का अध्ययन करने के लिए&gt; इमेजिंग तकनीक

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

Carotid Artery Infusions for Pharmacokinetic and Pharmacodynamic Analysis of Taxanes in Mice

चूहे में Taxanes के फार्माकोकाइनेटिक और pharmacodynamic विश्लेषण के लिए मन्या धमनी आधान

When proposing the use of a drug, drug combination, or drug delivery into a novel system, one must assess the pharmacokinetics of the drug in the study ...

Non-invasive Assessment of the Efficacy of New Therapeutics for Intestinal Pathologies Using Serial Endoscopic Imaging of Live Mice

लाइव चूहे के सीरियल इंडोस्कोपिक इमेजिंग का उपयोग आंतों विकृतियों के लिए नई चिकित्सा की प्रभावकारिता के गैर इनवेसिव आकलन

Animal models of inflammatory bowel disease (IBD) and colorectal cancer (CRC) have provided significant insight into the cell intrinsic and extrinsic ...

A Rat Carotid Balloon Injury Model to Test Anti-vascular Remodeling Therapeutics

एक चूहा मन्या गुब्बारा चोट मॉडल का परीक्षण करने के लिए एंटी-नाड़ी चिकित्सा Remodeling

The rat carotid balloon injury is a well-established surgical model that has been used to study arterial remodeling and vascular cell proliferation. It is ...

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics

लुकिंग ग्लास के माध्यम से: समय चूक माइक्रोस्कोपी और एकल कक्षों के अनुदैर्ध्य अध्ययन करने के लिए ट्रैकिंग विरोधी कैंसर चिकित्सा

The response of single cells to anti-cancer drugs contributes significantly in determining the population response, and therefore is a major contributing ...

Longitudinal In Vivo Imaging of the Cerebrovasculature: Relevance to CNS Diseases

Longitudinal In Vivo Imaging of the Cerebrovasculature: Relevance to CNS Diseases

अनुदैर्ध्य<em&gt; Vivo</em&gt; Cerebrovasculature की इमेजिंग: सीएनएस रोगों के लिए प्रासंगिकता

Remodeling of the brain vasculature is a common trait of brain pathologies. In vivo imaging techniques are fundamental to detect cerebrovascular ...

Evaluating the Procedure for Performing Awake Cystometry in a Mouse Model

एक माउस मॉडल में जागरण तंत्रिका कोशिका के प्रदर्शन की प्रक्रिया का मूल्यांकन करना

Awake filling cystometry has been used for a long time to evaluate bladder function in freely moving mice, however, the specific methods used, vary among ...

Intranasal Delivery of Therapeutic Stem Cells to Glioblastoma in a Mouse Model

एक माउस मॉडल में ग्लियोब्लास्टोमा के लिए चिकित्सीय स्टेम कोशिकाओं के इंट्रानेसल वितरण

The intrinsic tropism towards brain malignancies renders stem cells as promising carriers of therapeutic agents against malignant tumors. The delivery of ...

Novel Methods for Intranasal Administration Under Inhalation Anesthesia to Evaluate Nose-to-Brain Drug Delivery

Intranasal प्रशासन के लिए उपंयास तरीकों साँस लेना संज्ञाहरण के तहत नाक से मस्तिष्क दवा वितरण का मूल्यांकन करने के लिए

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