{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:15:56Z","timestamp":1790392556517,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2009,1,2]],"date-time":"2009-01-02T00:00:00Z","timestamp":1230854400000},"content-version":"vor","delay-in-days":123,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2008,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Objectives\/Hypothesis:<\/jats:bold> Hair cell loss results in the secondary loss of spiral ganglion neurons (SGNs), over a period of several weeks. The death of the SGNs themselves results from apoptosis. Previous studies have shown that several molecules are involved in the apoptosis of SGNs that occurred secondary to hair cell loss. However, the precise mechanism of apoptosis of the SGNs remains unclear. The aim of this study was to ascertain the secondary apoptosis of spiral ganglion cells induced by aminoglycoside and to investigate the role of the Fas\u2013FasL signaling pathway using guinea pigs as an experimental animal model.<\/jats:p><jats:p><jats:bold>Study Design:<\/jats:bold> Laboratory study using experimental animals.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Guinea pigs weighing 250 to 300 g (n = 21) from 3 to 4 weeks of age were used. Gentamicin (60 \u03bcL) was injected through a cochleostomy site on their left side. At 1 (n = 7), 2 (n = 7), and 3 (n = 7) weeks after gentamicin treatment, their cochleas were obtained from their temporal bone. Hematoxylin and eosin and terminal deoxynucleotidyl transferase\u2010mediated dUTP\u2010biotin nick\u2010end labeling staining were performed to observe apoptosis. To investigate the involvement of the Fas\u2013FasL signaling pathway in the secondary apoptosis of SGNs, we performed reverse transcription\u2010polymerase chain reaction (RT\u2010PCR), western blotting, and immunohistochemistry.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> A progressive loss of spiral ganglion cells with increasing time after gentamicin treatment was observed on light microscopic examination. Terminal deoxynucleotidyl transferase\u2010mediated dUTP\u2010biotin nick\u2010end labeling staining demonstrated induction of apoptotic cell death in SGNs after gentamicin treatment. Expression of FasL increased over time after gentamicin treatment as determined by RT\u2010PCR and western blotting. On immunohistochemical staining, we observed the localization of FasL in the SGNs. The proapoptotic molecules Bax and Bad were increased, but levels of the antiapoptotic molecule Bcl\u20102 were decreased at increasing survival times after gentamicin treatment on RT\u2010PCR. The gentamicin\u2010treated group displayed initial activation of caspase\u20108 and increased the cleavage of caspase\u20103, caspase\u20108, and PARP protein in a time\u2010dependent manner.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> The secondary apoptosis of SGNs could be a result of the apoptotic Fas\u2013FasL signaling pathway. Blocking the Fas\u2013FasL signaling pathway could be considered as a method for preventing secondary degeneration of SGNs, and further studies are needed to confirm this.<\/jats:p>","DOI":"10.1097\/mlg.0b013e31817c1303","type":"journal-article","created":{"date-parts":[[2008,8,27]],"date-time":"2008-08-27T07:18:27Z","timestamp":1219821507000},"page":"1659-1668","source":"Crossref","is-referenced-by-count":28,"title":["Secondary Apoptosis of Spiral Ganglion Cells Induced by Aminoglycoside: Fas\u2013Fas Ligand Signaling Pathway"],"prefix":"10.1002","volume":"118","author":[{"given":"Woo Yong","family":"Bae","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee Suk","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dae Young","family":"Hur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Wook","family":"Jeong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Ryong","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,2]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-200306000-00015"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.3109\/00016487409129731"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.3109\/00016487409129730"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1015434524040"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.03.098"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5955(99)00211-7"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(99)01983-6"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-200103000-00026"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00405-002-0459-9"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/35037728"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1025534223168"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1385-299X(02)00205-2"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1007201913730"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5955(00)00059-9"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5303.1132"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.179.3.873"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90326-L"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/6.10.1567"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90614-5"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90222-C"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7533326"},{"key":"e_1_2_6_23_2","doi-asserted-by":"crossref","first-page":"3806","DOI":"10.4049\/jimmunol.154.8.3806","article-title":"Expression of the Fas ligand in cells of T cell lineage.","volume":"154","author":"Suda T","year":"1995","journal-title":"J Immunol"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0300-483X(02)00007-0"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.11.6654"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1211\/0022357011776289"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(02)00143-1"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1159\/000071996"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-200303000-00012"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(99)02088-0"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)81004-1"}],"container-title":["The Laryngoscope"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1097%2FMLG.0b013e31817c1303","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1097\/MLG.0b013e31817c1303","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,8]],"date-time":"2023-10-08T21:02:49Z","timestamp":1696798969000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1097\/MLG.0b013e31817c1303"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,9]]},"references-count":30,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2008,9]]}},"alternative-id":["10.1097\/MLG.0b013e31817c1303"],"URL":"https:\/\/doi.org\/10.1097\/mlg.0b013e31817c1303","archive":["Portico"],"relation":{},"ISSN":["0023-852X","1531-4995"],"issn-type":[{"value":"0023-852X","type":"print"},{"value":"1531-4995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,9]]}}}