Name: a surgical procedure for the administration of drugs to the inner ear in a non-human primate common marmoset (callithrix jacchus)
Uploaded: 2018-02-27T12:30:00
Description: Watch this Scientific Journal Video about A Surgical Procedure for the Administration of Drugs to the Inner Ear in a Non-Human Primate Common Marmoset Callithrix jacchus at JoVE.com

Arbejdet er støttet af tilskud til MF fra den japanske regering MEXT KAKENHI (24592560, 15 H 04991 og 15 K 15624) og Takeda Science Foundation til MF og Jikei Universitet strategiske prioritering forskningsfonden til H.J.O.

Alle eksperimentelle procedurer blev udført på Jikei University, Tokyo Japan. Animalske håndtering og eksperimentelle procedurer blev godkendt af institutionelle Animal Care og bruge udvalg af det Jikei Universitet (godkendelse ingen: 26-060) og udført i overensstemmelse med de institutionelle retningslinjer for brugen af forsøgsdyr ved Jikei Universitet, som er enige med retningslinjerne for korrekt adfærd af dyr eksperimenter af videnskab Rådet af Japan (2006). Pasning af dyr blev gennemført i overensstemmelse med anbefalingerne i ...

<ol>
	<li>Liberman, M. C., Kujawa, S. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cochlear+synaptopathy+in+acquired+sensorineural+hearing+loss:+Manifestations+and+mechanisms.">Cochlear synaptopathy in acquired sensorineural hearing loss: Manifestations and mechanisms.</a> Hear Res. 349, 138-147 (2017).</li><li>World Health Organization. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Deafness and hearing loss (Fact sheet N8300). , (2015).</li><li>Thompson, D. 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=Universal+newborn+hearing+screening:+summary+of+evidence.">Universal newborn hearing screening: summary of evidence.</a> JAMA. 286 (16), 2000-2010 (2001).</li><li>Wang, X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neural+coding+strategies+in+auditory+cortex.">Neural coding strategies in auditory cortex.</a> Hear Res. 229 (1-2), 81-93 (2007).</li><li>Wang, X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=On+cortical+coding+of+vocal+communication+sounds+in+primates.">On cortical coding of vocal communication sounds in primates.</a> Proc Natl Acad Sci U S A. 97 (22), 11843-11849 (2000).</li><li>Bendor, D., Wang, X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+neuronal+representation+of+pitch+in+primate+auditory+cortex.">The neuronal representation of pitch in primate auditory cortex.</a> Nature. 436 (7054), 1161-1165 (2005).</li><li>Bendor, D., Wang, X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neural+coding+of+periodicity+in+marmoset+auditory+cortex.">Neural coding of periodicity in marmoset auditory cortex.</a> J Neurophysiol. 103 (4), 1809-1822 (2010).</li><li>Eliades, S. J., Wang, X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sensory-motor+interaction+in+the+primate+auditory+cortex+during+self-initiated+vocalizations.">Sensory-motor interaction in the primate auditory cortex during self-initiated vocalizations.</a> J Neurophysiol. 89 (4), 2194-2207 (2003).</li><li>Eliades, S. J., Wang, X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dynamics+of+auditory-vocal+interaction+in+monkey+auditory+cortex.">Dynamics of auditory-vocal interaction in monkey auditory cortex.</a> Cereb Cortex. 15 (10), 1510-1523 (2005).</li><li>Eliades, S. J., Wang, X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neural+substrates+of+vocalization+feedback+monitoring+in+primate+auditory+cortex.">Neural substrates of vocalization feedback monitoring in primate auditory cortex.</a> Nature. 453 (7198), 1102-1106 (2008).</li><li>Hosoya, M., Fujioka, M., Ogawa, K., Okano, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Distinct+Expression+Patterns+Of+Causative+Genes+Responsible+For+Hereditary+Progressive+Hearing+Loss+In+Non-Human+Primate+Cochlea.">Distinct Expression Patterns Of Causative Genes Responsible For Hereditary Progressive Hearing Loss In Non-Human Primate Cochlea.</a> Sci Rep. 6, 22250 (2016).</li><li>Hosoya, M., Fujioka, M., Kobayashi, R., Okano, H., Ogawa, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Overlapping+expression+of+anion+exchangers+in+the+cochlea+of+a+non-human+primate+suggests+functional+compensation.">Overlapping expression of anion exchangers in the cochlea of a non-human primate suggests functional compensation.</a> Neurosci Res. 110, 1-10 (2016).</li><li>Sasaki, 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=Generation+of+transgenic+non-human+primates+with+germline+transmission.">Generation of transgenic non-human primates with germline transmission.</a> Nature. 459 (7246), 523-527 (2009).</li><li>Sato, K., 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=Generation+of+a+Nonhuman+Primate+Model+of+Severe+Combined+Immunodeficiency+Using+Highly+Efficient+Genome+Editing.">Generation of a Nonhuman Primate Model of Severe Combined Immunodeficiency Using Highly Efficient Genome Editing.</a> Cell Stem Cell. 19 (1), 127-138 (2016).</li><li>Sasaki, 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=Establishment+of+novel+embryonic+stem+cell+lines+derived+from+the+common+marmoset+(Callithrix+jacchus).">Establishment of novel embryonic stem cell lines derived from the common marmoset (Callithrix jacchus).</a> Stem Cells. 23 (9), 1304-1313 (2005).</li><li>Tomioka, I., 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=Generating+induced+pluripotent+stem+cells+from+common+marmoset+(Callithrix+jacchus)+fetal+liver+cells+using+defined+factors,+including+Lin28.">Generating induced pluripotent stem cells from common marmoset (Callithrix jacchus) fetal liver cells using defined factors, including Lin28.</a> Genes Cells. 15 (9), 959-969 (2010).</li><li>Harada, T., Tokuriki, M. <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+click+intensity+and+frequency+on+the+brain-stem+auditory+evoked+potentials+in+the+common+marmoset+(Callithrix+jacchus).">Effects of click intensity and frequency on the brain-stem auditory evoked potentials in the common marmoset (Callithrix jacchus).</a> J Vet Med Sci. 59 (7), 561-567 (1997).</li><li>Harada, T., Tokuriki, M., Tanioka, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Age-related+changes+in+the+brainstem+auditory+evoked+potentials+of+the+marmoset.">Age-related changes in the brainstem auditory evoked potentials of the marmoset.</a> Hear Res. 128 (1-2), 119-124 (1999).</li><li>Juhn, S. K., Hunter, B. A., Odland, R. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Blood-labyrinth+barrier+and+fluid+dynamics+of+the+inner+ear.">Blood-labyrinth barrier and fluid dynamics of the inner ear.</a> Int Tinnitus J. 7 (2), 72-83 (2001).</li><li>Nakashima, T., 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=Disorders+of+cochlear+blood+flow.">Disorders of cochlear blood flow.</a> Brain Res Brain Res Rev. 43 (1), 17-28 (2003).</li><li>Akil, O., Rouse, S. L., Chan, D. K., Lustig, L. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Surgical+method+for+virally+mediated+gene+delivery+to+the+mouse+inner+ear+through+the+round+window+membrane.">Surgical method for virally mediated gene delivery to the mouse inner ear through the round window membrane.</a> J Vis Exp. (97), (2015).</li><li>Jero, J., Tseng, C. J., Mhatre, A. N., Lalwani, A. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+surgical+approach+appropriate+for+targeted+cochlear+gene+therapy+in+the+mouse.">A surgical approach appropriate for targeted cochlear gene therapy in the mouse.</a> Hear Res. 151 (1-2), 106-114 (2001).</li><li>Iizuka, T., 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=Noninvasive+in+vivo+delivery+of+transgene+via+adeno-associated+virus+into+supporting+cells+of+the+neonatal+mouse+cochlea.">Noninvasive in vivo delivery of transgene via adeno-associated virus into supporting cells of the neonatal mouse cochlea.</a> Hum Gene Ther. 19 (4), 384-390 (2008).</li><li>Kilpatrick, L. 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=Adeno-associated+virus-mediated+gene+delivery+into+the+scala+media+of+the+normal+and+deafened+adult+mouse+ear.">Adeno-associated virus-mediated gene delivery into the scala media of the normal and deafened adult mouse ear.</a> Gene Ther. 18 (6), 569-578 (2011).</li><li>Yamasoba, T., Yagi, M., Roessler, B. J., Miller, J. M., Raphael, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Inner+ear+transgene+expression+after+adenoviral+vector+inoculation+in+the+endolymphatic+sac.">Inner ear transgene expression after adenoviral vector inoculation in the endolymphatic sac.</a> Hum Gene Ther. 10 (5), 769-774 (1999).</li><li>Kawamoto, K., Oh, S. H., Kanzaki, S., Brown, N., Raphael, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+functional+and+structural+outcome+of+inner+ear+gene+transfer+via+the+vestibular+and+cochlear+fluids+in+mice.">The functional and structural outcome of inner ear gene transfer via the vestibular and cochlear fluids in mice.</a> Mol Ther. 4 (6), 575-585 (2001).</li><li>Praetorius, M., Baker, K., Weich, C. M., Plinkert, P. K., Staecker, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hearing+preservation+after+inner+ear+gene+therapy:+the+effect+of+vector+and+surgical+approach.">Hearing preservation after inner ear gene therapy: the effect of vector and surgical approach.</a> ORL J Otorhinolaryngol Relat Spec. 65 (4), 211-214 (2003).</li><li>Nakagawa, T., 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=Topical+insulin-like+growth+factor+1+treatment+using+gelatin+hydrogels+for+glucocorticoid-resistant+sudden+sensorineural+hearing+loss:+a+prospective+clinical+trial.">Topical insulin-like growth factor 1 treatment using gelatin hydrogels for glucocorticoid-resistant sudden sensorineural hearing loss: a prospective clinical trial.</a> BMC Med. 8, 76 (2010).</li><li>Piu, F., 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=OTO-104:+a+sustained-release+dexamethasone+hydrogel+for+the+treatment+of+otic+disorders.">OTO-104: a sustained-release dexamethasone hydrogel for the treatment of otic disorders.</a> Otol Neurotol. 32 (1), 171-179 (2011).</li><li>Plontke, S. K., 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=double+blind,+placebo+controlled+trial+on+the+safety+and+efficacy+of+continuous+intratympanic+dexamethasone+delivered+via+a+round+window+catheter+for+severe+to+profound+sudden+idiopathic+sensorineural+hearing+loss+after+failure+of+systemic+therapy.">double blind, placebo controlled trial on the safety and efficacy of continuous intratympanic dexamethasone delivered via a round window catheter for severe to profound sudden idiopathic sensorineural hearing loss after failure of systemic therapy.</a> Laryngoscope. 119 (2), 359-369 (2009).</li><li>Wenzel, G. I., Warnecke, A., Stover, T., Lenarz, T. <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+extracochlear+gacyclidine+perfusion+on+tinnitus+in+humans:+a+case+series.">Effects of extracochlear gacyclidine perfusion on tinnitus in humans: a case series.</a> Eur Arch Otorhinolaryngol. 267 (5), 691-699 (2010).</li></ol>

Mængden af cochlear blodgennemstrømningen er ekstremt små, anslået til at være i størrelsesordenen 1/1.000.000 af de samlede minutvolumen i mennesker, og er begrænset af tilstedeværelsen af blod-cochlea barriere, der adskiller det indre øre fra den generelle cirkulation19 ,20. Af disse grunde er stof eller viral vektor administration i det indre øre gunstige, ikke via systemisk administration men snarere ved direkte administration. I mus og marsvin eks...

Perceptivt høretab (SNHL) opstår overvejende fra skader eller mangel i øresneglen. Almindelige årsager til SNHL omfatter aldring (fx presbycusis), genetiske defekter, eksponering for høj støj, infektion og ototoksiske narkotika1. Verdenssundhedsorganisationen (WHO) anslås, at over 360 mio mennesker, svarende til 5.3% af verdens befolkning lider af høre tab2. Det vurderes også, 1 i 900 til 1 i 2.500 nyfødte har moderat, svær, og dyb medfødt permanent høretab, og omkring en ud af tre voksne over 65 år har en vis grad af høring tab3. Der er imidlertid ingen effektiv klinisk behandling af høretab til disse patienter.
Hørelse forskning har længe udført ved hjælp af gnaver eller marsvin modeller, og mange tilgange, såsom genterapi og regenerativ terapi, er blevet foreslået som en ny behandling af høretab. Men der er stor forskel mellem mennesker og gnavere i form af det auditive system, og det er meget vanskeligt at oversætte dyremodeller for humane ansøgninger. Den fælles silkeabe (C. jacchus), en New World abe stammer fra Amazonas, er blevet et attraktivt primat model for forskellige grundlæggende undersøgelser af flere årsager. Først, dens anatomi og fysiologi er mere ligner dem af mennesker snarere end gnavere. Andet, de grundlæggende biologiske oplysninger om denne art, herunder sygdomme, neurale netværk, adfærd og genomet, er godt præget. Auditive og vocal forarbejdning, kortikal kodning af hyppighed, repræsentation af banen og auditive-vokal interaktioner af fælles silkeaber har også været rapporteret4,5,6,7 , 8 , 9 , 10. i de seneste histologiske undersøgelser, forskerne identificerede karakteristiske udtryk mønstre af 20 døvhed gener og anion vekslere i cochlea af den fælles silkeabe og fandt, at fem gener, som er sygdomsfremkaldende for progressiv døvhed og tre anion varmevekslere, havde forskellige udtryk mønstre fra dem af gnavere11,12. Disse profiler føre os til at tro, at den fælles silkeabe er et kraftfuldt værktøj til høring forskning.
De mest markante attributter af den fælles silkeabe som en eksperimentel dyr er som følger:
<ul><li>Nem håndtering med en lille kropsstørrelse i forhold til nogle arter af gamle verden aber: voksen silkeaber vejer 300-400 g og er ca 60 cm i højden, hvilket svarer til rotter.</li>
	<li>Stærkt reproduktive primat: silkeaber attain seksuelle modenhed i en alder af 18 måneder og er i stand til at bære to gange om året og producere 4 til 6 afkom årligt.</li>
	<li>Genetiske modifikationer er tilgængelige: Sasaki E et al. formået at skabe transgene13 og knock-out14 primater bruger silkeaber af genetiske modifikationer impliceret i neurologiske lidelser (fx Parkinson's sygdom og Alzheimers sygdom).</li>
	<li>Både embryonale stamceller (ES) og inducerede pluripotente stamceller (iPS) er blevet etableret15,16. Selvom det er temmelig svært at holde det samme antal silkeaber i forhold til gnavere, giver adgang til stamceller eller iPS-celler in vitro- assays, hvilket vil reducere antallet af i vivo assays kræves.</li>
</ul>For at lette bedre Translationel forskning i døvhed og dens potentielle terapi, etableret vi en billeddannelse undersøgelse protokollen ved hjælp af CT og Mr, generel anæstesi og høreprøver ved hjælp af auditive hjernestammen svar (ABRs). Disse eksperimentelle systemer kan give os bedre muligheder for at få præ-klinisk bevis koncept undersøgelser, som er afgørende for broer over kløfter mellem gnaver undersøgelser og kliniske forsøg. Her rapporterer vi en kirurgisk metode til at administrere medicin til det indre øre af den fælles silkeabe gennem det runde vindue membran. For at få et klart overblik omkring det runde vindue, uden at manipulere trommehinden, der kan forårsage et konduktivt høretab, er det nyttigt at tilgang fra mastoid hulrummet. Klinisk, omtales denne tilgang, som "posterior tympanotomy" er veletableret og normalt anvendes til cochlear implantation og cholesteatoma kirurgi. Vi mener, at bageste tympanotomy gør det muligt at udføre præcis administration af medicin uden inducerende høretab.

<table border="0" cellpadding="0" cellspacing="0" style="width:675px;" width="674">
	<colgroup>
		<col />
		<col />
		<col />
		<col />
	</colgroup>
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">common marmoset</td>
			<td style="width:92px;">CLEA Japan</td>
			<td style="width:160px;">EDM:C.Marmoset(Jic)</td>
			<td style="width:207px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">isoflurane</td>
			<td style="width:92px;">Phizer</td>
			<td style="width:160px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">medetomidine</td>
			<td style="width:92px;">ZENOAQ</td>
			<td style="width:160px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">midazolam</td>
			<td style="width:92px;">astellas</td>
			<td style="width:160px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">butorphanol</td>
			<td style="width:92px;">Meiji Seika</td>
			<td style="width:160px;"></td>
			<td></td>
		</tr>
		<tr height="24">
			<td height="24" style="height:24px;width:216px;">ampicillin</td>
			<td style="width:92px;">Meiji Seika</td>
			<td style="width:160px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">lidocaine hydrochloride</td>
			<td style="width:92px;">AstraZeneca</td>
			<td style="width:160px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">&#160;6-0 absorbent thread</td>
			<td style="width:92px;">ETHICON</td>
			<td style="width:160px;">RD-1</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">atipamezole hydrochloride</td>
			<td style="width:92px;">ZENOAQ</td>
			<td style="width:160px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">phosphate buffered saline</td>
			<td style="width:92px;">Wako</td>
			<td style="width:160px;">045-29795</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Surge Wave</td>
			<td style="width:92px;">Morita</td>
			<td style="width:160px;">TR-900-OR</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Diamond Bar 006</td>
			<td style="width:92px;">Morita</td>
			<td style="width:160px;">14070057</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Diamond Bar 010</td>
			<td style="width:92px;">Morita</td>
			<td style="width:160px;">14070081</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">intensive care unit</td>
			<td style="width:92px;">Menix</td>
			<td style="width:160px;">P-100</td>
			<td></td>
		</tr>
	</tbody>
</table>

a surgical procedure for the administration of drugs to the inner ear in a non-human primate common marmoset (callithrix jacchus)

Høre forskning er længe blevet fremmet af gnavere modeller, selv om nogle sygdomme, menneskelige symptomer ikke kan blive sammenfattet. Den fælles silkeabe (Callithrix jacchus) er en lille, let at håndtere New World abe, som har en lignende anatomi af den tidsmæssige knoglen, herunder mellemøret ossicular kæder og indre øre til mennesker, end i forhold til gnavere. Her, rapportere vi en reproducerbar, sikker og rationel kirurgisk tilgang til cochlear runde vinduet niche for medicinafgivelse til det indre øre af den fælles silkeabe. Vi vedtog bageste tympanotomy, en procedure, der anvendes klinisk i menneskelige kirurgi, for at undgå manipulation af trommehinden, der kan forårsage konduktivt høretab. Denne kirurgiske procedure førte ikke til nogen betydelig høretab. Denne tilgang var mulig på grund af den store bulla struktur af den fælles silkeabe, selv om den laterale halvrunde kanalen og lodrette del af ansigtets nerve bør overvejes nøje. Denne kirurgiske metode gør det muligt for os at udføre sikker og præcis administration af medicin uden tab af hørelse, som er af stor betydning at få præ-klinisk påvisning i id for Translationel forskning.

Bageste tympanotomy blev udført uden komplikationer såsom operationsstedet infektion, blødning med vaskulære skade eller vestibulær dysfunktion, som undertiden opstår med mellemøret manipulation. Vi udførte bageste tympanotomy på 7-årige fælles silkeabe højre øre og administreres 1 µL af fosfatbufferet saltopløsning til runde vinduet niche. ABRs blev målt før og to måneder efter operationen (figur 5A-B). Waveforms og tærskl...

Watch this Scientific Journal Video about A Surgical Procedure for the Administration of Drugs to the Inner Ear in a Non-Human Primate Common Marmoset Callithrix jacchus at JoVE.com

A Surgical Procedure for the Administration of Drugs to the Inner Ear in a Non-Human Primate Common Marmoset Callithrix jacchus

Vi rapporterer en kirurgisk metode til at administrere medicin til det indre øre af en ikke-menneskelige primater, den fælles silkeabe (Callithrix jacchus), via det runde vindue membran.

En kirurgisk Procedure for Administration af medicin til det indre øre i en ikke-menneskelige primater fælles silkeabe (Callithrix jacchus)

Hearing research has long been facilitated by rodent models, although in some diseases, human symptoms cannot be recapitulated. The common marmoset ...

The overall goal of this surgical procedure is to evaluate the effects of specific drugs of interest on the hearing function of non-human primate common marmoset through their safe administration into the inner ear without inducing hearing loss. This method can help answer key questions about inner ear drug delivery, including how to open the master cavity and where to deliver the drug. The main advantage of this technique is that the inner ear can be a plus without complications, which is critical for evaluating the efficiency of inner ear treatments in primates.The implications of this technique extend towards the study of potential therapies for human deafness, as the auditory system of the marmoset is quite similar to that of humans. The masteration of this method is critical and the posture and anatomy is difficult to learn and require that small window to be created in the narrow space without damaging the facial knob or the ossicular chain. Confirm the appropriate level of sedation by toe pinch and place the animal in the supine position on a heating mat with the head and neck extended.Fix maxilla to the table with nylon thread and pull out the tongue. Insert an endotracheal tube along the laryngeal surface of the epiglottis. Check the entitle carbon dioxide level in the endotracheal tube to confirm that the tube has been properly placed within the trachea and secure the tube to the animal's face.Incline the head to the 30 to 45 degree angle toward the non-operative side and shave the postauricular region of the operative side of the animal Then disinfect the postauricular region and the external auditory canal with povidone iodine and cover the animal with a surgical drape sheet with a round opening over the surgical area. Before opening the skin inject 1%of lidocaine hydrochloride subcutaneously to the incision site. Then, using a surgical microscope and a number 15 round shaped blade, make an incision into the postauricular skin and apply pressure to the bleeding area with a gauze soaked in one to 5, 000 diluted epinephrine.Open the soft tissue of the postauricular region so that the auricular cartilage and the postauricular muscle can be identified and expose the external auditory canal bone deep within the cartilage. To confirm the depth of the tympanic membrane, expose the bony part of the tympanic rim and peel the postauricular muscles toward the caudal aspect to separate the muscles from the temporal bone. Expose the lateral surface of the temporal bone and use a one millimeter diamond burr to make a hole approximately five millimeters behind the external auditory canal.Drill further to enlarge the hole as appropriate and locate the horizontal semi-circular canal, which bulges toward the mastoid cavity. Then drill and remove any bone septa as necessary to obtain a clear view of the facial recess, located at the center of the triangular area between the facial nerve and the corded tympany. Using a 0.6 millimeter diameter diamond burr at 1, 000 rpm, drill a small hole between the vertical section of the facial nerve, which appears as a pink line through the thinned bone and the tympanic rim.Stop the drilling just before the nerve is exposed as a white line structure and confirm that the round window niche can be visualized through the hold. Using a 25 gauge or thinner needle, deliver the drugs of interest into the niche and cover the niche with an appropriate miscues solution to ensure the drug is retained. Confirm that hemostasis is securely controlled and use six o absorbent threads to close the epidermal and dermal layers with simple, interrupted sutures.Then place a piece of gauze onto the surgical wound, fix the gauze in place with a bandage, and allow the marmoset to recover in an intensive care unit at 37 degrees Celsius in 30%oxygen until complete arousal. In these graphs, the auditory brain stem responses of a seven year old common marmoset before and two months after the delivery of one microliter of PBS to the round window niche, as just demonstrated, are shown. Comparison of these wave forms and thresholds to a previous study demonstrated no changes in these parameters before or after the surgery, confirming that posterior tympanotomy is a safe and useful procedure for drug administration to the round window niche of the common marmoset.Once mastered, this technique can be completed in an hour, including the anesthesia and induction, if it's performed properly. While attempting this procedure, it's important to remember not to damage the ossicle or the facial knob which can result in conductive hearing loss or facial paralysis respectively. After its development, this technique paved the way for researchers in the field of the translation research to test potential new therapies for hearing loss.After watching this video, you should have a good understanding of how to approach the inner ear of the common marmoset safely and to administer the drug into round window niche properly.

Research

JoVE Journal

Medicine

A Surgical Procedure for the Administration of Drugs to the Inner Ear in a Non-Human Primate Common Marmoset (Callithrix jacchus)

A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia

There are several lines of evidence supporting the role of de novo mutations as a mechanism for common disorders, such as autism and schizophrenia. First, ...

Development of an Audio-based Virtual Gaming Environment to Assist with Navigation Skills in the Blind

Udvikling af en Audio-based Virtual Gaming Miljø til at hjælpe med Navigation Skills i Blind

Audio-based Environment Simulator (AbES) is virtual environment software designed to improve real world navigation skills in the blind. Using only audio ...

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

Heterotop Mucosal transplantere Procedure for direkte Drug Delivery til Brain i mus

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 ...

A Surgical Procedure for Resecting the Mouse Rib: A Model for Large-Scale Long Bone Repair

Et kirurgisk indgreb for resektion musen Rib: En model for storstilet lang knogle Repair

This protocol introduces researchers to a new model for large-scale bone repair utilizing the mouse rib. The procedure details the following: preparation ...

Performing Permanent Distal Middle Cerebral with Common Carotid Artery Occlusion in Aged Rats to Study Cortical Ischemia with Sustained Disability

Udførelse Permanent Distal Mellemøsten Cerebral med Common Arteria carotis Okklusion i Aged Rotter at studere Kortikal Iskæmi med vedvarende handicap

Stroke typically occurs in elderly people with a range of comorbidities including carotid (or other arterial) atherosclerosis, high blood pressure, ...

A Novel Murine Model of Arteriovenous Fistula Failure: The Surgical Procedure in Detail

A Novel murin model af arteriovenøs fistel Fejl: den kirurgiske procedure i Detail

The arteriovenous fistula (AVF) still suffers from a high number of failures caused by insufficient remodeling and intimal hyperplasia from which the ...

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

Brug Saccadometry med Deep Brain Stimulation at studere normal og patologisk Brain Function

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

In Vivo Gene Transfer to the Rabbit Common Carotid Artery Endothelium

In Vivo Gene Transfer to the Rabbit Common Carotid Artery Endothelium

In Vivo Genoverførsel til kanin fælles halspulsåren endotelet

The goal of this method is to introduce a transgene into the endothelium of isolated segments of both rabbit common carotid arteries. The method achieves ...

Retinal Pigment Epithelium Transplantation in a Non-human Primate Model for Degenerative Retinal Diseases

Retinal Pigment Epitel Transplantation i en ikke-human primat model for degenerative retinale sygdomme

Retinal pigment epithelial (RPE) transplantation holds great promise for the treatment of inherited and acquired retinal degenerative diseases. These ...

Behavioral and Network Pharmacology-Based Analyses for the Traditional Mongolian Medicine Zadi-5 in a Rat Model of Depression

Adfærds- og netværksfarmakologiske analyser for den traditionelle mongolske medicin Zadi-5 i en rottemodel for depression

Zadi-5 is a traditional Mongolian medicine that is widely used for the treatment of depression and symptoms of irritation. Although the therapeutic ...