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Because calcineurin is known to activate cell death pathways and is controlled by Ca<jats:sup>2+<\/jats:sup> and calmodulin, this study assessed the role of calcineurin in auditory hair cell death in guinea pigs after intense noise exposure. Immediately after noise exposure (4\u2010kHz octave band, 120 dB, for 5 hr), a population of hair cells exhibited calcineurin immunoreactivity at the cuticular plate, with a decreasing number of positive\u2010stained cells on Days 1\u20133. By Day 7, the levels of calcineurin immunoreactivity had diminished to near control, non\u2010noise exposed values, concomitant with an increasing loss of hair cells. Staining of hair cell nuclei with propidium iodide (PI), restricted to calcineurin\u2010immunopositive cells, indicated breakdown of cell membranes symptomatic of incipient cell death. The local application of the calcineurin inhibitors, FK506 and cyclosporin A, reduced the level of noise\u2010induced auditory brain stem response threshold shift and hair cell death, indicating that calcineurin is a factor in noise\u2010induced hearing loss. The results suggest that calcineurin inhibitors are of potential therapeutic value for long\u2010term protection of the morphologic integrity and function of the organ of Corti against noise trauma. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.20267","type":"journal-article","created":{"date-parts":[[2004,8,27]],"date-time":"2004-08-27T22:31:57Z","timestamp":1093645917000},"page":"383-392","source":"Crossref","is-referenced-by-count":65,"title":["Calcineurin activation contributes to noise\u2010induced hearing loss"],"prefix":"10.1002","volume":"78","author":[{"given":"Shujiro B.","family":"Minami","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Yamashita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Schacht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef 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