Molecular mechanisms involved in cochlear implantation trauma and the protection of hearing and auditory sensory cells by inhibition of c-jun-N-terminal kinase signaling
Objectives/Hypothesis: To investigate the molecular mechanisms involved in electrode insertion trauma (EIT) and to test the otoprotective effect of locally delivered AM‐111. Study Design: An animal model of cochlear implantation. Methods: Guinea pigs' hearing thresholds were measured by auditor...
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| Veröffentlicht in: | The Laryngoscope 2013-03, Vol.123 (S1), p.S1-S14 |
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| creator | Eshraghi, Adrien A. Gupta, Chhavi Van De Water, Thomas R. Bohorquez, Jorge E. Garnham, Carolyn Bas, Esperanza Talamo, Victoria Maria |
| description | Objectives/Hypothesis:
To investigate the molecular mechanisms involved in electrode insertion trauma (EIT) and to test the otoprotective effect of locally delivered AM‐111.
Study Design:
An animal model of cochlear implantation.
Methods:
Guinea pigs' hearing thresholds were measured by auditory brainstem response (ABR) before and after cochlear implantation in four groups: EIT; pretreated with hyaluronate gel 30 minutes before EIT (EIT+Gel); pretreated with hyaluronate gel/AM‐111 30 minutes before EIT (EIT+AM‐111); and unoperated contralateral ears as controls. Neurofilament, synapsin, and fluorescein isothiocyanate (FITC)‐phalloidin staining for hair cell counts were performed at 90 days post‐EIT. Immunostaining for 4‐hydroxy‐2‐nonenal (HNE), activated caspase‐3, CellROX, and phospho‐c‐Jun were performed at 24 hours post‐EIT.
Results:
ABR thresholds increased post‐EIT in the cochleae of EIT only and EIT+Gel treated animals. There was no significant increase in hearing thresholds in cochleae from either EIT+AM‐111 treated or unoperated control ears. AM‐111 protection of organ of Corti sensory elements (i.e., hair cells [HCs], supporting cells [SCs], nerve fibers, and synapses) was documented at 3 months post‐EIT. Immunostaining of 24‐hour post‐EIT specimens demonstrated increased levels of HNE in HCs and SCs; increased levels of CellROX and activation of caspase‐3 was observed only in SCs, and phosphorylation of c‐Jun occurred only in HCs of the EIT‐only and EIT+Gel specimens. There was no immunostaining for either HNE, CellROX, caspase‐3, or phospho‐c‐Jun in the organ of Corti specimens from AM‐111 treated cochleae.
Conclusions:
Molecular mechanisms involved in programmed cell death of HCs are different than the ones involved in programmed cell death of SCs. Local delivery of AM‐111 provided a significant level of protection against EIT‐induced hearing losses, HC losses, and damage to neural elements. Laryngoscope, 123:S1–S14, 2013 |
| doi_str_mv | 10.1002/lary.23902 |
| format | Article |
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To investigate the molecular mechanisms involved in electrode insertion trauma (EIT) and to test the otoprotective effect of locally delivered AM‐111.
Study Design:
An animal model of cochlear implantation.
Methods:
Guinea pigs' hearing thresholds were measured by auditory brainstem response (ABR) before and after cochlear implantation in four groups: EIT; pretreated with hyaluronate gel 30 minutes before EIT (EIT+Gel); pretreated with hyaluronate gel/AM‐111 30 minutes before EIT (EIT+AM‐111); and unoperated contralateral ears as controls. Neurofilament, synapsin, and fluorescein isothiocyanate (FITC)‐phalloidin staining for hair cell counts were performed at 90 days post‐EIT. Immunostaining for 4‐hydroxy‐2‐nonenal (HNE), activated caspase‐3, CellROX, and phospho‐c‐Jun were performed at 24 hours post‐EIT.
Results:
ABR thresholds increased post‐EIT in the cochleae of EIT only and EIT+Gel treated animals. There was no significant increase in hearing thresholds in cochleae from either EIT+AM‐111 treated or unoperated control ears. AM‐111 protection of organ of Corti sensory elements (i.e., hair cells [HCs], supporting cells [SCs], nerve fibers, and synapses) was documented at 3 months post‐EIT. Immunostaining of 24‐hour post‐EIT specimens demonstrated increased levels of HNE in HCs and SCs; increased levels of CellROX and activation of caspase‐3 was observed only in SCs, and phosphorylation of c‐Jun occurred only in HCs of the EIT‐only and EIT+Gel specimens. There was no immunostaining for either HNE, CellROX, caspase‐3, or phospho‐c‐Jun in the organ of Corti specimens from AM‐111 treated cochleae.
Conclusions:
Molecular mechanisms involved in programmed cell death of HCs are different than the ones involved in programmed cell death of SCs. Local delivery of AM‐111 provided a significant level of protection against EIT‐induced hearing losses, HC losses, and damage to neural elements. Laryngoscope, 123:S1–S14, 2013</description><identifier>ISSN: 0023-852X</identifier><identifier>EISSN: 1531-4995</identifier><identifier>DOI: 10.1002/lary.23902</identifier><identifier>PMID: 23382052</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Aldehydes - analysis ; Alginates ; Animals ; Apoptosis ; Auditory Threshold ; Caspase 3 - analysis ; Cell Count ; Cell Death - physiology ; Cochlear implant ; Cochlear Implantation - adverse effects ; electrode insertion trauma ; Electrodes - adverse effects ; Evoked Potentials, Auditory, Brain Stem ; Guinea Pigs ; Hair Cells, Auditory - cytology ; Hair Cells, Auditory - drug effects ; Hair Cells, Auditory - physiology ; Hearing loss ; hearing preservation ; Hyaluronic Acid ; Immunohistochemistry ; inner ear trauma ; JNK Mitogen-Activated Protein Kinases - physiology ; Medical research ; Organ of Corti - drug effects ; Peptides - pharmacology ; Signal Transduction</subject><ispartof>The Laryngoscope, 2013-03, Vol.123 (S1), p.S1-S14</ispartof><rights>Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4612-600ba49495a91984afa9746b57ca9fe3dfe1d79d7524085de07982af529009513</citedby><cites>FETCH-LOGICAL-c4612-600ba49495a91984afa9746b57ca9fe3dfe1d79d7524085de07982af529009513</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Flary.23902$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Flary.23902$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23382052$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Eshraghi, Adrien A.</creatorcontrib><creatorcontrib>Gupta, Chhavi</creatorcontrib><creatorcontrib>Van De Water, Thomas R.</creatorcontrib><creatorcontrib>Bohorquez, Jorge E.</creatorcontrib><creatorcontrib>Garnham, Carolyn</creatorcontrib><creatorcontrib>Bas, Esperanza</creatorcontrib><creatorcontrib>Talamo, Victoria Maria</creatorcontrib><title>Molecular mechanisms involved in cochlear implantation trauma and the protection of hearing and auditory sensory cells by inhibition of c-jun-N-terminal kinase signaling</title><title>The Laryngoscope</title><addtitle>The Laryngoscope</addtitle><description>Objectives/Hypothesis:
To investigate the molecular mechanisms involved in electrode insertion trauma (EIT) and to test the otoprotective effect of locally delivered AM‐111.
Study Design:
An animal model of cochlear implantation.
Methods:
Guinea pigs' hearing thresholds were measured by auditory brainstem response (ABR) before and after cochlear implantation in four groups: EIT; pretreated with hyaluronate gel 30 minutes before EIT (EIT+Gel); pretreated with hyaluronate gel/AM‐111 30 minutes before EIT (EIT+AM‐111); and unoperated contralateral ears as controls. Neurofilament, synapsin, and fluorescein isothiocyanate (FITC)‐phalloidin staining for hair cell counts were performed at 90 days post‐EIT. Immunostaining for 4‐hydroxy‐2‐nonenal (HNE), activated caspase‐3, CellROX, and phospho‐c‐Jun were performed at 24 hours post‐EIT.
Results:
ABR thresholds increased post‐EIT in the cochleae of EIT only and EIT+Gel treated animals. There was no significant increase in hearing thresholds in cochleae from either EIT+AM‐111 treated or unoperated control ears. AM‐111 protection of organ of Corti sensory elements (i.e., hair cells [HCs], supporting cells [SCs], nerve fibers, and synapses) was documented at 3 months post‐EIT. Immunostaining of 24‐hour post‐EIT specimens demonstrated increased levels of HNE in HCs and SCs; increased levels of CellROX and activation of caspase‐3 was observed only in SCs, and phosphorylation of c‐Jun occurred only in HCs of the EIT‐only and EIT+Gel specimens. There was no immunostaining for either HNE, CellROX, caspase‐3, or phospho‐c‐Jun in the organ of Corti specimens from AM‐111 treated cochleae.
Conclusions:
Molecular mechanisms involved in programmed cell death of HCs are different than the ones involved in programmed cell death of SCs. Local delivery of AM‐111 provided a significant level of protection against EIT‐induced hearing losses, HC losses, and damage to neural elements. Laryngoscope, 123:S1–S14, 2013</description><subject>Aldehydes - analysis</subject><subject>Alginates</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Auditory Threshold</subject><subject>Caspase 3 - analysis</subject><subject>Cell Count</subject><subject>Cell Death - physiology</subject><subject>Cochlear implant</subject><subject>Cochlear Implantation - adverse effects</subject><subject>electrode insertion trauma</subject><subject>Electrodes - adverse effects</subject><subject>Evoked Potentials, Auditory, Brain Stem</subject><subject>Guinea Pigs</subject><subject>Hair Cells, Auditory - cytology</subject><subject>Hair Cells, Auditory - drug effects</subject><subject>Hair Cells, Auditory - physiology</subject><subject>Hearing loss</subject><subject>hearing preservation</subject><subject>Hyaluronic Acid</subject><subject>Immunohistochemistry</subject><subject>inner ear trauma</subject><subject>JNK Mitogen-Activated Protein Kinases - physiology</subject><subject>Medical research</subject><subject>Organ of Corti - drug effects</subject><subject>Peptides - pharmacology</subject><subject>Signal Transduction</subject><issn>0023-852X</issn><issn>1531-4995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1u1DAUhS0EokNhwwMgS2wQUop_4jheVhXTIs0UhPhdWY7jNJ469tRO2s4j8ZZ4ZjpdsGDja-t85-haB4DXGJ1ghMgHp-LmhFCByBMww4ziohSCPQWzLNKiZuTXEXiR0gohzClDz8ERobQmiJEZ-LMMzugpR8DB6F55m4YErb8N7ta0-QJ10L0zWbfD2ik_qtEGD8eopkFB5Vs49gauYxiN3imhg33Grb_aqWpq7RjiBibj03Zq41yCzSZn97axB48uVpMvLovRxMF65eB1PpOByV7lV057CZ51yiXz6mEeg-_zj9_OLorF5_NPZ6eLQpcVJkWFUKNKUQqmBBZ1qToleFk1jGslOkPbzuCWi5YzUqKatQZxURPVMSIQEgzTY_Bun5v_dDOZNMrBpu3SypswJYkpLmvBeIUy-vYfdBWmmNfdUbwUOJeSqfd7SseQUjSdXEc75M4kRnJboNwWKHcFZvjNQ-TUDKZ9RA-NZQDvgTvrzOY_UXJx-vX3IbTYe2wazf2jR8VrWXHKmfx5eS6_LC9-LJbzuWT0L97mt_c</recordid><startdate>201303</startdate><enddate>201303</enddate><creator>Eshraghi, Adrien A.</creator><creator>Gupta, Chhavi</creator><creator>Van De Water, Thomas R.</creator><creator>Bohorquez, Jorge E.</creator><creator>Garnham, Carolyn</creator><creator>Bas, Esperanza</creator><creator>Talamo, Victoria Maria</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><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>K9.</scope><scope>7X8</scope></search><sort><creationdate>201303</creationdate><title>Molecular mechanisms involved in cochlear implantation trauma and the protection of hearing and auditory sensory cells by inhibition of c-jun-N-terminal kinase signaling</title><author>Eshraghi, Adrien A. ; Gupta, Chhavi ; Van De Water, Thomas R. ; Bohorquez, Jorge E. ; Garnham, Carolyn ; Bas, Esperanza ; Talamo, Victoria Maria</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4612-600ba49495a91984afa9746b57ca9fe3dfe1d79d7524085de07982af529009513</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Aldehydes - analysis</topic><topic>Alginates</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Auditory Threshold</topic><topic>Caspase 3 - analysis</topic><topic>Cell Count</topic><topic>Cell Death - physiology</topic><topic>Cochlear implant</topic><topic>Cochlear Implantation - adverse effects</topic><topic>electrode insertion trauma</topic><topic>Electrodes - adverse effects</topic><topic>Evoked Potentials, Auditory, Brain Stem</topic><topic>Guinea Pigs</topic><topic>Hair Cells, Auditory - cytology</topic><topic>Hair Cells, Auditory - drug effects</topic><topic>Hair Cells, Auditory - physiology</topic><topic>Hearing loss</topic><topic>hearing preservation</topic><topic>Hyaluronic Acid</topic><topic>Immunohistochemistry</topic><topic>inner ear trauma</topic><topic>JNK Mitogen-Activated Protein Kinases - physiology</topic><topic>Medical research</topic><topic>Organ of Corti - drug effects</topic><topic>Peptides - pharmacology</topic><topic>Signal Transduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Eshraghi, Adrien A.</creatorcontrib><creatorcontrib>Gupta, Chhavi</creatorcontrib><creatorcontrib>Van De Water, Thomas R.</creatorcontrib><creatorcontrib>Bohorquez, Jorge E.</creatorcontrib><creatorcontrib>Garnham, Carolyn</creatorcontrib><creatorcontrib>Bas, Esperanza</creatorcontrib><creatorcontrib>Talamo, Victoria Maria</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>The Laryngoscope</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Eshraghi, Adrien A.</au><au>Gupta, Chhavi</au><au>Van De Water, Thomas R.</au><au>Bohorquez, Jorge E.</au><au>Garnham, Carolyn</au><au>Bas, Esperanza</au><au>Talamo, Victoria Maria</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Molecular mechanisms involved in cochlear implantation trauma and the protection of hearing and auditory sensory cells by inhibition of c-jun-N-terminal kinase signaling</atitle><jtitle>The Laryngoscope</jtitle><addtitle>The Laryngoscope</addtitle><date>2013-03</date><risdate>2013</risdate><volume>123</volume><issue>S1</issue><spage>S1</spage><epage>S14</epage><pages>S1-S14</pages><issn>0023-852X</issn><eissn>1531-4995</eissn><abstract>Objectives/Hypothesis:
To investigate the molecular mechanisms involved in electrode insertion trauma (EIT) and to test the otoprotective effect of locally delivered AM‐111.
Study Design:
An animal model of cochlear implantation.
Methods:
Guinea pigs' hearing thresholds were measured by auditory brainstem response (ABR) before and after cochlear implantation in four groups: EIT; pretreated with hyaluronate gel 30 minutes before EIT (EIT+Gel); pretreated with hyaluronate gel/AM‐111 30 minutes before EIT (EIT+AM‐111); and unoperated contralateral ears as controls. Neurofilament, synapsin, and fluorescein isothiocyanate (FITC)‐phalloidin staining for hair cell counts were performed at 90 days post‐EIT. Immunostaining for 4‐hydroxy‐2‐nonenal (HNE), activated caspase‐3, CellROX, and phospho‐c‐Jun were performed at 24 hours post‐EIT.
Results:
ABR thresholds increased post‐EIT in the cochleae of EIT only and EIT+Gel treated animals. There was no significant increase in hearing thresholds in cochleae from either EIT+AM‐111 treated or unoperated control ears. AM‐111 protection of organ of Corti sensory elements (i.e., hair cells [HCs], supporting cells [SCs], nerve fibers, and synapses) was documented at 3 months post‐EIT. Immunostaining of 24‐hour post‐EIT specimens demonstrated increased levels of HNE in HCs and SCs; increased levels of CellROX and activation of caspase‐3 was observed only in SCs, and phosphorylation of c‐Jun occurred only in HCs of the EIT‐only and EIT+Gel specimens. There was no immunostaining for either HNE, CellROX, caspase‐3, or phospho‐c‐Jun in the organ of Corti specimens from AM‐111 treated cochleae.
Conclusions:
Molecular mechanisms involved in programmed cell death of HCs are different than the ones involved in programmed cell death of SCs. Local delivery of AM‐111 provided a significant level of protection against EIT‐induced hearing losses, HC losses, and damage to neural elements. Laryngoscope, 123:S1–S14, 2013</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>23382052</pmid><doi>10.1002/lary.23902</doi><tpages>14</tpages></addata></record> |
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| ispartof | The Laryngoscope, 2013-03, Vol.123 (S1), p.S1-S14 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Aldehydes - analysis Alginates Animals Apoptosis Auditory Threshold Caspase 3 - analysis Cell Count Cell Death - physiology Cochlear implant Cochlear Implantation - adverse effects electrode insertion trauma Electrodes - adverse effects Evoked Potentials, Auditory, Brain Stem Guinea Pigs Hair Cells, Auditory - cytology Hair Cells, Auditory - drug effects Hair Cells, Auditory - physiology Hearing loss hearing preservation Hyaluronic Acid Immunohistochemistry inner ear trauma JNK Mitogen-Activated Protein Kinases - physiology Medical research Organ of Corti - drug effects Peptides - pharmacology Signal Transduction |
| title | Molecular mechanisms involved in cochlear implantation trauma and the protection of hearing and auditory sensory cells by inhibition of c-jun-N-terminal kinase signaling |
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