Drug delivery into the cochlear apex: Improved control to sequentially affect finely spaced regions along the entire length of the cochlear spiral
•A new method to pharmacologically affect the cochlea is described.•Solutions are administered from a pipette sealed into the cochlear apex.•Controlled injections drive solutions towards the cochlear aqueduct in the base.•The method better controls drug concentrations than conventional cochlear perf...
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| Veröffentlicht in: | Journal of neuroscience methods 2016-11, Vol.273, p.201-209 |
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| container_title | Journal of neuroscience methods |
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| creator | Lichtenhan, J.T. Hartsock, J. Dornhoffer, J.R. Donovan, K.M. Salt, A.N. |
| description | •A new method to pharmacologically affect the cochlea is described.•Solutions are administered from a pipette sealed into the cochlear apex.•Controlled injections drive solutions towards the cochlear aqueduct in the base.•The method better controls drug concentrations than conventional cochlear perfusion.•Responses from finely spaced stimulus frequencies (∼16 per octave) were affected.1.
Administering pharmaceuticals to the scala tympani of the inner ear is a common approach to study cochlear physiology and mechanics. We present here a novel method for in vivo drug delivery in a controlled manner to sealed ears.
Injections of ototoxic solutions were applied from a pipette sealed into a fenestra in the cochlear apex, progressively driving solutions along the length of scala tympani toward the cochlear aqueduct at the base. Drugs can be delivered rapidly or slowly. In this report we focus on slow delivery in which the injection rate is automatically adjusted to account for varying cross sectional area of the scala tympani, therefore driving a solution front at uniform rate.
Objective measurements originating from finely spaced, low- to high-characteristic cochlear frequency places were sequentially affected. Comparison with existing methods(s): Controlled administration of pharmaceuticals into the cochlear apex overcomes a number of serious limitations of previously established methods such as cochlear perfusions with an injection pipette in the cochlear base: The drug concentration achieved is more precisely controlled, drug concentrations remain in scala tympani and are not rapidly washed out by cerebrospinal fluid flow, and the entire length of the cochlear spiral can be treated quickly or slowly with time.
Controlled administration of solutions into the cochlear apex can be a powerful approach to sequentially effect objective measurements originating from finely spaced cochlear regions and allows, for the first time, the spatial origin of CAPs to be objectively defined. |
| doi_str_mv | 10.1016/j.jneumeth.2016.08.005 |
| format | Article |
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Administering pharmaceuticals to the scala tympani of the inner ear is a common approach to study cochlear physiology and mechanics. We present here a novel method for in vivo drug delivery in a controlled manner to sealed ears.
Injections of ototoxic solutions were applied from a pipette sealed into a fenestra in the cochlear apex, progressively driving solutions along the length of scala tympani toward the cochlear aqueduct at the base. Drugs can be delivered rapidly or slowly. In this report we focus on slow delivery in which the injection rate is automatically adjusted to account for varying cross sectional area of the scala tympani, therefore driving a solution front at uniform rate.
Objective measurements originating from finely spaced, low- to high-characteristic cochlear frequency places were sequentially affected. Comparison with existing methods(s): Controlled administration of pharmaceuticals into the cochlear apex overcomes a number of serious limitations of previously established methods such as cochlear perfusions with an injection pipette in the cochlear base: The drug concentration achieved is more precisely controlled, drug concentrations remain in scala tympani and are not rapidly washed out by cerebrospinal fluid flow, and the entire length of the cochlear spiral can be treated quickly or slowly with time.
Controlled administration of solutions into the cochlear apex can be a powerful approach to sequentially effect objective measurements originating from finely spaced cochlear regions and allows, for the first time, the spatial origin of CAPs to be objectively defined.</description><identifier>ISSN: 0165-0270</identifier><identifier>EISSN: 1872-678X</identifier><identifier>DOI: 10.1016/j.jneumeth.2016.08.005</identifier><identifier>PMID: 27506463</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Acoustic Stimulation ; Acoustics ; Action Potentials - drug effects ; Animals ; Auditory nerve overlapped waveform ; Cochlear action potential ; Cochlear fluid ; Cochlear perfusion ; Dextrans - administration & dosage ; Dextrans - pharmacokinetics ; Drug Delivery Systems ; Excitatory Amino Acid Agonists - administration & dosage ; Female ; Fluorescein-5-isothiocyanate - administration & dosage ; Fluorescein-5-isothiocyanate - analogs & derivatives ; Fluorescein-5-isothiocyanate - pharmacokinetics ; Guinea Pigs ; Kainic acid ; Kainic Acid - administration & dosage ; Male ; Otoacoustic Emissions, Spontaneous - drug effects ; Scala Tympani - drug effects ; Scala Tympani - metabolism ; Time Factors</subject><ispartof>Journal of neuroscience methods, 2016-11, Vol.273, p.201-209</ispartof><rights>2016 Elsevier B.V.</rights><rights>Copyright © 2016 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c471t-d61e6b8da504cf020d80e3deaa4c52b0a10c3e3f203ed7c12f8698357d6e07953</citedby><cites>FETCH-LOGICAL-c471t-d61e6b8da504cf020d80e3deaa4c52b0a10c3e3f203ed7c12f8698357d6e07953</cites><orcidid>0000-0001-9705-6905 ; 0000-0002-5265-0895 ; 0000-0001-8871-8655</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jneumeth.2016.08.005$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27506463$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lichtenhan, J.T.</creatorcontrib><creatorcontrib>Hartsock, J.</creatorcontrib><creatorcontrib>Dornhoffer, J.R.</creatorcontrib><creatorcontrib>Donovan, K.M.</creatorcontrib><creatorcontrib>Salt, A.N.</creatorcontrib><title>Drug delivery into the cochlear apex: Improved control to sequentially affect finely spaced regions along the entire length of the cochlear spiral</title><title>Journal of neuroscience methods</title><addtitle>J Neurosci Methods</addtitle><description>•A new method to pharmacologically affect the cochlea is described.•Solutions are administered from a pipette sealed into the cochlear apex.•Controlled injections drive solutions towards the cochlear aqueduct in the base.•The method better controls drug concentrations than conventional cochlear perfusion.•Responses from finely spaced stimulus frequencies (∼16 per octave) were affected.1.
Administering pharmaceuticals to the scala tympani of the inner ear is a common approach to study cochlear physiology and mechanics. We present here a novel method for in vivo drug delivery in a controlled manner to sealed ears.
Injections of ototoxic solutions were applied from a pipette sealed into a fenestra in the cochlear apex, progressively driving solutions along the length of scala tympani toward the cochlear aqueduct at the base. Drugs can be delivered rapidly or slowly. In this report we focus on slow delivery in which the injection rate is automatically adjusted to account for varying cross sectional area of the scala tympani, therefore driving a solution front at uniform rate.
Objective measurements originating from finely spaced, low- to high-characteristic cochlear frequency places were sequentially affected. Comparison with existing methods(s): Controlled administration of pharmaceuticals into the cochlear apex overcomes a number of serious limitations of previously established methods such as cochlear perfusions with an injection pipette in the cochlear base: The drug concentration achieved is more precisely controlled, drug concentrations remain in scala tympani and are not rapidly washed out by cerebrospinal fluid flow, and the entire length of the cochlear spiral can be treated quickly or slowly with time.
Controlled administration of solutions into the cochlear apex can be a powerful approach to sequentially effect objective measurements originating from finely spaced cochlear regions and allows, for the first time, the spatial origin of CAPs to be objectively defined.</description><subject>Acoustic Stimulation</subject><subject>Acoustics</subject><subject>Action Potentials - drug effects</subject><subject>Animals</subject><subject>Auditory nerve overlapped waveform</subject><subject>Cochlear action potential</subject><subject>Cochlear fluid</subject><subject>Cochlear perfusion</subject><subject>Dextrans - administration & dosage</subject><subject>Dextrans - pharmacokinetics</subject><subject>Drug Delivery Systems</subject><subject>Excitatory Amino Acid Agonists - administration & dosage</subject><subject>Female</subject><subject>Fluorescein-5-isothiocyanate - administration & dosage</subject><subject>Fluorescein-5-isothiocyanate - analogs & derivatives</subject><subject>Fluorescein-5-isothiocyanate - pharmacokinetics</subject><subject>Guinea Pigs</subject><subject>Kainic acid</subject><subject>Kainic Acid - administration & dosage</subject><subject>Male</subject><subject>Otoacoustic Emissions, Spontaneous - drug effects</subject><subject>Scala Tympani - drug effects</subject><subject>Scala Tympani - metabolism</subject><subject>Time Factors</subject><issn>0165-0270</issn><issn>1872-678X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcFu1DAQhi0EokvhFSofuSQdJ7GTcECgQqFSJS4gcbO8ziTxyrGDnay6r8ET42Xbip44WeP5Zv7R_xNywSBnwMTlLt85XCdcxrxIdQ5NDsCfkQ1r6iITdfPzOdmkBs-gqOGMvIpxBwBVC-IlOStqDqIS5Yb8_hTWgXZozR7DgRq3eLqMSLXXo0UVqJrx7h29mebg99ilf7cEb2nCIv5a0S1GWXugqu9RL7Q3DlMVZ6UTHHAw3kWqrHfD37VHPiC16IZlpL5_qhVnE5R9TV70ykZ8c_-ekx_Xn79ffc1uv325ufp4m-mqZkvWCYZi23SKQ6V7KKBrAMsOlao0L7agGOgSy76AErtas6JvRNuUvO4EQt3y8py8P-2d1-2EnU63JXU5BzOpcJBeGfm048woB7-XHGpetSIteHu_IPhkRVzkZKJGa5VDv0bJkhovWVuUCRUnVAcfY8D-UYaBPAYqd_IhUHkMVEIjU6Bp8OLfIx_HHhJMwIcTgMmqvcEgozbokv3JaL3Izpv_afwB1j-6VQ</recordid><startdate>20161101</startdate><enddate>20161101</enddate><creator>Lichtenhan, J.T.</creator><creator>Hartsock, J.</creator><creator>Dornhoffer, J.R.</creator><creator>Donovan, K.M.</creator><creator>Salt, A.N.</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-9705-6905</orcidid><orcidid>https://orcid.org/0000-0002-5265-0895</orcidid><orcidid>https://orcid.org/0000-0001-8871-8655</orcidid></search><sort><creationdate>20161101</creationdate><title>Drug delivery into the cochlear apex: Improved control to sequentially affect finely spaced regions along the entire length of the cochlear spiral</title><author>Lichtenhan, J.T. ; Hartsock, J. ; Dornhoffer, J.R. ; Donovan, K.M. ; Salt, A.N.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c471t-d61e6b8da504cf020d80e3deaa4c52b0a10c3e3f203ed7c12f8698357d6e07953</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Acoustic Stimulation</topic><topic>Acoustics</topic><topic>Action Potentials - drug effects</topic><topic>Animals</topic><topic>Auditory nerve overlapped waveform</topic><topic>Cochlear action potential</topic><topic>Cochlear fluid</topic><topic>Cochlear perfusion</topic><topic>Dextrans - administration & dosage</topic><topic>Dextrans - pharmacokinetics</topic><topic>Drug Delivery Systems</topic><topic>Excitatory Amino Acid Agonists - administration & dosage</topic><topic>Female</topic><topic>Fluorescein-5-isothiocyanate - administration & dosage</topic><topic>Fluorescein-5-isothiocyanate - analogs & derivatives</topic><topic>Fluorescein-5-isothiocyanate - pharmacokinetics</topic><topic>Guinea Pigs</topic><topic>Kainic acid</topic><topic>Kainic Acid - administration & dosage</topic><topic>Male</topic><topic>Otoacoustic Emissions, Spontaneous - drug effects</topic><topic>Scala Tympani - drug effects</topic><topic>Scala Tympani - metabolism</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lichtenhan, J.T.</creatorcontrib><creatorcontrib>Hartsock, J.</creatorcontrib><creatorcontrib>Dornhoffer, J.R.</creatorcontrib><creatorcontrib>Donovan, K.M.</creatorcontrib><creatorcontrib>Salt, A.N.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of neuroscience methods</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lichtenhan, J.T.</au><au>Hartsock, J.</au><au>Dornhoffer, J.R.</au><au>Donovan, K.M.</au><au>Salt, A.N.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Drug delivery into the cochlear apex: Improved control to sequentially affect finely spaced regions along the entire length of the cochlear spiral</atitle><jtitle>Journal of neuroscience methods</jtitle><addtitle>J Neurosci Methods</addtitle><date>2016-11-01</date><risdate>2016</risdate><volume>273</volume><spage>201</spage><epage>209</epage><pages>201-209</pages><issn>0165-0270</issn><eissn>1872-678X</eissn><abstract>•A new method to pharmacologically affect the cochlea is described.•Solutions are administered from a pipette sealed into the cochlear apex.•Controlled injections drive solutions towards the cochlear aqueduct in the base.•The method better controls drug concentrations than conventional cochlear perfusion.•Responses from finely spaced stimulus frequencies (∼16 per octave) were affected.1.
Administering pharmaceuticals to the scala tympani of the inner ear is a common approach to study cochlear physiology and mechanics. We present here a novel method for in vivo drug delivery in a controlled manner to sealed ears.
Injections of ototoxic solutions were applied from a pipette sealed into a fenestra in the cochlear apex, progressively driving solutions along the length of scala tympani toward the cochlear aqueduct at the base. Drugs can be delivered rapidly or slowly. In this report we focus on slow delivery in which the injection rate is automatically adjusted to account for varying cross sectional area of the scala tympani, therefore driving a solution front at uniform rate.
Objective measurements originating from finely spaced, low- to high-characteristic cochlear frequency places were sequentially affected. Comparison with existing methods(s): Controlled administration of pharmaceuticals into the cochlear apex overcomes a number of serious limitations of previously established methods such as cochlear perfusions with an injection pipette in the cochlear base: The drug concentration achieved is more precisely controlled, drug concentrations remain in scala tympani and are not rapidly washed out by cerebrospinal fluid flow, and the entire length of the cochlear spiral can be treated quickly or slowly with time.
Controlled administration of solutions into the cochlear apex can be a powerful approach to sequentially effect objective measurements originating from finely spaced cochlear regions and allows, for the first time, the spatial origin of CAPs to be objectively defined.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>27506463</pmid><doi>10.1016/j.jneumeth.2016.08.005</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-9705-6905</orcidid><orcidid>https://orcid.org/0000-0002-5265-0895</orcidid><orcidid>https://orcid.org/0000-0001-8871-8655</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of neuroscience methods, 2016-11, Vol.273, p.201-209 |
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| language | eng |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Acoustic Stimulation Acoustics Action Potentials - drug effects Animals Auditory nerve overlapped waveform Cochlear action potential Cochlear fluid Cochlear perfusion Dextrans - administration & dosage Dextrans - pharmacokinetics Drug Delivery Systems Excitatory Amino Acid Agonists - administration & dosage Female Fluorescein-5-isothiocyanate - administration & dosage Fluorescein-5-isothiocyanate - analogs & derivatives Fluorescein-5-isothiocyanate - pharmacokinetics Guinea Pigs Kainic acid Kainic Acid - administration & dosage Male Otoacoustic Emissions, Spontaneous - drug effects Scala Tympani - drug effects Scala Tympani - metabolism Time Factors |
| title | Drug delivery into the cochlear apex: Improved control to sequentially affect finely spaced regions along the entire length of the cochlear spiral |
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