Bu makalede açıklanan çalışma ncı RO1 CA166907, NIDCD RO1-DC 002396 ve RO3 DC011621 tarafından desteklenmiştir.

Erkek Wistar fareler Ulusal Sağlık Enstitüleri hayvan uygun olarak ele kullanma yönergeleri ve Southern Illinois Üniversitesi okul tıp laboratuvar hayvan bakımı ve kullanmak Komitesi tarafından onaylanmış bir iletişim kuralı. İşitsel beyin sapı davranım Odyometrisi (ABR), trans-tympanic ilaç dağıtım etkisini doğrulamak için önce ilaç idaresi ve 72 h sonra anestezi altında fareler üzerinde gerçekleştirildi.
1. işitsel beyin sapı davranım Odyometrisi (ABR)
Not: ABR ölçümleri işitsel test cihazları ve yazılım kullanılarak toplanmıştır. ABR uyarılmış potansiyeller veya yüksek frekanslı dalgalar sekizinci kranial sinir tarafından oluşturulan temsil eder (dalga ı ve II) ve anteroventral koklear çekirdeği (dalga III), lateral lemniscus (dalga IV) ve inferior gibi daha yüksek diğer işitsel beyin sapı yapıları olacaklar (dalga V). Bu dalgalar gecikme süresi bağlı olarak farklı. ABR ölçümleri12daha önce açıklandığı gibi yapıldı.
<ol><li>Fareler 90 mg/kg ketamin ve 17 mg/kg xylazine üzerinden mayi enjeksiyon karışımı ile anestezi. Anestezi ile ayak-çimdik refleks derinliği onaylayın. Oftalmik yağlama (veya madeni yağ damla) gözlerinin kurumasını önlemek ve ülserasyon anestezi sırasında önlemek için her iki gözde uygulanır.</li>
	<li>Yüzükoyun kontrollü bir akustik kabin içinde bir Isıtma yastık (37 ° C) üzerinde fareyi yerleştirin. Odyoloji test etme donanımları dışında ve kabine yanında yer alır.</li>
	<li>Paslanmaz çelik elektrotlar buna göre ekle: zemin elektrot arka kanat, doğrudan kafatası tepesine iki kulak ve her kulak pinna aşağıda negatif elektrotlar arasında pozitif elektrot.</li>
	<li>Akustik uyaranlara 5 ms sesi patlama 8, 16 ve 32 kHz olarak yüksek frekans dönüştürücü kullanarak uygulayın. Uyarıcı yoğunluklarda desibel ses basınç seviyesi (dB SPL) belirleyin. Bu 10 dB SPL başlar ve 90 dB SPL bir 10-dB adım boyu ile ulaşır. Bir dürtü hassas ses seviyesi ölçer kullanarak 90 dB SPL maksimum çıkış ses yoğunluklarda kalibre. Not: Test sonucu periferik işitme organı, koklea ve söz konusu işitsel yapıları bütünlüğünü bir göstergesi verir. Dalga biçimleri uyarıcı giriş 15 ms içinde oluşturulur ve sırayla üç kritik faktörler tarafından düzenlenir ve tel zaman dalgalar gecikme süresi bağlıdır: beyin, yoğunluğu ve frekans ses hacmi. İşitsel uyarılmış potansiyeller yazılım üreticisi tarafından sağlanan kullanarak kaydedildi.</li>
	<li>İki farklı dalga biçimleri (II ve III) 0.5 µV genlik, eşik olarak belirgin uyandırmak en düşük yoğunluk göz önünde bulundurun. Not: Eşik üst karakter sonra tedavi tedavi öncesi elde edilen eşik ile karşılaştırıldığında ölçülen eşik farkı temsil eder.</li>
</ol>2. Trans-Tympanic enjeksiyon
<ol><li>Trans-tympanically ilacı vermek için fareyi sol yanal dekübitus pozisyonda yerleştirin.<ol>
<li>2.5 mm tek kullanımlık kulak ayna kulak kanalı içine yerleştirin.</li>
		<li>Böylece kulak zarı görülebilir bir cerrahi kapsam kullanımı ile Ayna getirin.</li>
		<li>29 G X ½, 0.5 mL insülin şırınga, kullanarak çizdiğiniz [R] - N - fenil izopropil adenozin 50 µL kadar (R-PIA) çözüm (1 µM), 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX) çözüm (3 µM) veya (5 adet) enjekte siRNA çözüm (0.9 µg).</li>
		<li>Kulak zarı ön alt bölgeye iğne yönlendirmek için ayna kullanın.</li>
		<li>İğne ile membran delik poke ve 1.2.3 içinde belirtilen uyuşturucu yönetmek. Fareyi 15 dakika bu pozisyonda dinlenmek izin verir. Not: 50 µL kulak zarı sığdırmak için yeterli güç olması gerekir. Hiçbir sıvı içinde belgili tanımlık kulak kanal yönetim sonra olmalıdır.</li>
		<li>Fareyi sağ yanal dekübitus getirin ve diğer kulakta Yönetim için adımları 1.2.1 1.2.5 aracılığıyla yineleyin yerleştirin.</li>
	</ol>
</li>
	<li>Sisplatin intraperitoneally alma sıçanlara sırtüstü pozisyonda 37 ° C'de bir Isıtma yastık üzerinde fareyi yer<ol>
<li>21 G X 3/4 kullanarak iğne (12" uzunluğu boru) cevap ver, sisplatin (11 mg/kg, 1 mg/mL steril fosfat tampon serum [PBS] çözümde) çekmek.</li>
		<li>Bir şırınga pompa kullanarak, sisplatin (1 mg/mL) ile mayi enjeksiyon 30 dk yönetmek. Not: 250 g sıçan için birimin 2.75 mL yaklaşık 0.1 mL min başına oranında olacaktır.</li>
	</ol>
</li>
	<li>Bu yordamları boyunca anestezi derinliği izlemeye devam edin. Sisplatin yönetim tamamlandıktan sonra fare geri onun nefes engel bir şey olmadığına emin yapma yüzükoyun, kafeste yerleştirin.</li>
	<li>Tamamen iyileşti kadar fare izleyin.</li>
</ol>3. koklea diseksiyon ve kalsiyumun
<ol><li>(Sonra 72 h) son ABR fareyi 90 mg/kg ketamin ve 17 mg/kg xylazine üzerinden mayi enjeksiyon karışımı ile anestezi. Anestezi ayak-çimdik refleks ile onaylayın. İşten çıkarma yolu ile sıçan ötenazi.</li>
	<li>Temporal13daha önce açıklandığı gibi kemik incelemek.</li>
	<li>Koklea (koklea tamamen kaplayan) 7-mL cam mercek şişe çözümde PBS x 1 %4 paraformaldehyde yerleştirin. Gecede 4 ° C'de soğutmak Paraformaldehyde kaldırmak ve oda sıcaklığında 1 x PBS ile yıkayın.</li>
	<li>PBS çıkartın ve tüp tamamen EDTA (pH 7.3) 120-mM çözüm ile doldurun. Oda sıcaklığında bir rotator yerleştirin ve 2-3 hafta, EDTA çözüm her gün değişen incelemelerine izin.</li>
</ol>4. Cryosectioning
<ol><li>Kalsiyumun tamamlandığında, aşağıdaki çözümleri (7 mL her) koklea 24 h 4 ° c % 10 Sükroz, % 20 Sükroz, % 20 sukroz ve bileşik katıştırma en uygun kesme sıcaklık (OCT) 1:1 karışımı için tamamen bırakın.</li>
	<li>Taze OCT bileşik doldurup tamamen koklea içinde bir 15 x 15 mm x 5 mm kalıp katıştırma tek kullanımlık kapak koyun. Koklea kendi tarafında Whitlon ve arktarafından açıklandığı gibi gömme kalıp alt paralel gelecek şekilde yönlendirin. 14
</li>
	<li>Hemen kalıp OKT kuvvetlendirmek ve-80 ° C'de gecede depolamak için Kuru Buza koyun.</li>
	<li>Mikroskop slaytları % 0,01 bırakın Poly-L lizin, oda sıcaklığında 30 dk. Kaldır slaytları, değil durulayın ve kuru gecede için izin. Bu slayt için cryosections kullanın.</li>
	<li>Koklea Ekim-80 ° C dondurucudan çıkarın ve kuru buza yerleştirin. Bir keskin microtome bıçak (L x W: 80 mm x 8 mm, kalınlık 0.25 mm, kesme açısı 34 °), kullanarak bölüm 10 µm-30 ° C'de bir cryostat kullanarak, OCT blokları Slayt başına iki bölüme yerleştirin.</li>
	<li>Ne zaman tamamlanmak 4 ° C'de slaytlar buzdolabında bekletin.</li>
</ol>5. immünhistokimya
<ol><li>Slaytları bir slayt raf tabak boyama cam mikroskop kaymak yerleştirin. Çanak 350 mL 1 x PBS ile doldurulması ve 5 min için slaytlar üç kez oda sıcaklığında yıkayın.</li>
	<li>Slaytlar çanağı kaldırmak ve doku kuru değil emin olmak bir Kuru Temizleme işlemi kullanarak doku çevresi kapalı kuru.<ol>
<li>Sıvı engelleme kalemi, doku bölümü bir daire çizin.</li>
	</ol>
</li>
	<li>Oda sıcaklığında 1 h için doku 150 µL % 10 normal (eşek) serum, % 1 Noniyonik deterjan ve 1 x PBS % 1 BSA içeren engelleme çözümün ekleyerek engellemek.</li>
	<li>Dokunun fazla engelleme çözüm ve doku gecede 4 ° C'de % 10 normal (eşek) serum, % 0,1 Noniyonik deterjan ve birincil antikor (aşağıdaki nota bakın) 150 µL ile oksijen odasında kuluçkaya 1 x PBS içinde. Not: Aşağıdaki antikorlar için bu dilutions kullanıldı: Şekil 2 ve 3, p-STAT1 Ser727 1:300. Şekil 4, p-STAT1 Ser727, 1: 100 ve TRPV1 1: 100.</li>
	<li>Slaytları bir slayt raf tabak boyama cam mikroskop kaymak yerleştirin. Çanak 350 mL 1 x PBS ile doldurulması ve slaytlar 5 min için üç kez oda sıcaklığında yıkayın.</li>
	<li>% 0,01 Noniyonik deterjan ve 1 x PBS oksijen odası karanlık oda sıcaklığında 2-3 h için % 10 normal (eşek) serum içeren bir çözüm içinde seyreltilmiş ikincil antikorlar ile kuluçkaya. Not: Aşağıdaki ikincil antikorlar için bu dilutions kullanıldı: Şekil 2 ve 3, Anti-tavşan eşek IgG 1:600. Şekil 4için 1:500 rodamine (TRITC) eşek Anti-tavşan IgG ve eşek Anti-keçi IgG 1:500.</li>
	<li>Slaytları bir slayt raf tabak boyama cam mikroskop kaymak yerleştirin. Çanak 350 mL 1 x PBS ile doldurulması ve slaytlar 5 min için üç kez oda sıcaklığında yıkayın.</li>
	<li>Aşırı sıvı slaydın dışına dokunun ve slayt etrafında doku kuru bir bezle kurulayın. Slaytlar DAPI montaj aracıyla doğrudan doku üzerine bir damla ekleyerek bağlayın. Yavaş yavaş üzerine hava kabarcığı yok altında kurulan sağlanması, coverslip yerleştirin ve slaytlar gecede karanlık oda sıcaklığında tedavi sağlar. Slaytları 4 ° C'de depolama</li>
	<li>Görüntü confocal mikroskobu kullanarak slaytlar. Aşağıdaki gibi görüntüleme için lazer kullanır: UV lazer DAPI, 488 nm lazer için anti-tavşan eşek IgG ve 543 nm lazer rodamine TRITC için.</li>
</ol>

<ol>
	<li>McKeage, M. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparative+adverse+effect+profiles+of+platinum+drugs.">Comparative adverse effect profiles of platinum drugs.</a> Drug Saf. 13 (4), 228-244 (1995).</li><li>Boulikas, T., Vougiouka, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cisplatin+and+platinum+drugs+at+the+molecular+level.">Cisplatin and platinum drugs at the molecular level.</a> Oncol Rep. 10 (6), 1663-1682 (2003).</li><li>Fouladi, M., 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=Phase+II+study+of+oxaliplatin+in+children+with+recurrent+or+refractory+medulloblastoma,+supratentorial+primitive+neuroectodermal+tumors,+and+atypical+teratoid+rhabdoid+tumors:+a+pediatric+brain+tumor+consortium+study.">Phase II study of oxaliplatin in children with recurrent or refractory medulloblastoma, supratentorial primitive neuroectodermal tumors, and atypical teratoid rhabdoid tumors: a pediatric brain tumor consortium study.</a> Cancer. 107 (9), 2291-2297 (2006).</li><li>Pasetto, L. M., D'Andrea, M. R., Rossi, E., Monfardini, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Oxaliplatin-related+neurotoxicity:+how+and+why.">Oxaliplatin-related neurotoxicity: how and why.</a> Crit Rev Oncol Hematol. 59 (2), 159-168 (2006).</li><li>Ardizzoni, 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=Cisplatin-+versus+carboplatin-based+chemotherapy+in+first-line+treatment+of+advanced+non-small-cell+lung+cancer:+an+individual+patient+data+meta-analysis.">Cisplatin- versus carboplatin-based chemotherapy in first-line treatment of advanced non-small-cell lung cancer: an individual patient data meta-analysis.</a> J Natl Cancer Inst. 99 (11), 847-857 (2007).</li><li>Banfi, B., Malgrange, B., Knisz, J., Steger, K., Dubois-Dauphin, M., Krause, K. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=NOX3,+a+superoxide-generating+NADPH+oxidase+of+the+inner+ear.">NOX3, a superoxide-generating NADPH oxidase of the inner ear.</a> J Biol Chem. 279 (44), 46065-46072 (2004).</li><li>Mukherjea, D., Whitworth, C. A., Nandish, S., Dunaway, G. A., Rybak, L. P., Ramkumar, V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Expression+of+the+kidney+injury+molecule+1+in+the+rat+cochlea+and+induction+by+cisplatin.">Expression of the kidney injury molecule 1 in the rat cochlea and induction by cisplatin.</a> Neuroscience. 139 (2), 733-740 (2006).</li><li>Rybak, L. P., Husain, K., Morris, C., Whitworth, C., Somani, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+of+protective+agents+against+cisplatin+ototoxicity.">Effect of protective agents against cisplatin ototoxicity.</a> Am J Otol. 21 (4), 513-520 (2000).</li><li>Lee, J. 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=Role+of+reactive+radicals+in+degeneration+of+the+auditory+system+of+mice+following+cisplatin+treatment.">Role of reactive radicals in degeneration of the auditory system of mice following cisplatin treatment.</a> Acta Otolaryngol. 124 (10), 1131-1135 (2004).</li><li>Lee, J. 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=Mechanisms+of+apoptosis+induced+by+cisplatin+in+marginal+cells+in+mouse+stria+vascularis.">Mechanisms of apoptosis induced by cisplatin in marginal cells in mouse stria vascularis.</a> ORL J Otorhinolaryngol Relat Spec. 66 (3), 111-118 (2004).</li><li>Lawenda, B. D., Kelly, K. M., Ladas, E. J., Sagar, S. M., Vickers, A., Blumberg, J. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Should+supplemental+antioxidant+administration+be+avoided+during+chemotherapy+and+radiation+therapy.">Should supplemental antioxidant administration be avoided during chemotherapy and radiation therapy.</a> J Natl Cancer Inst. 100 (11), 773-783 (2008).</li><li>Akil, O., Oursler, A. E., Fan, 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=Mouse+auditory+brainstem+response+testing.">Mouse auditory brainstem response testing.</a> Bio Protoc. 6 (6), 1768 (2016).</li><li>Montgomery, S. C., Cox, B. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Whole+Mount+Dissection+and+Immunofluorescence+of+the+Adult+Mouse+Cochlea.">Whole Mount Dissection and Immunofluorescence of the Adult Mouse Cochlea.</a> J. Vis. Exp. (107), e53561 (2016).</li><li>Whitlon, D. S., Szakaly, R., Greiner, M. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cryoembedding+and+sectioning+of+cochleas+for+immunocytochemistry+and+in+situ+hybridization.">Cryoembedding and sectioning of cochleas for immunocytochemistry and in situ hybridization.</a> Brain Res Brain Res Protoc. 6 (3), 159-166 (2001).</li><li>Londos, C., Cooper, D. M., Wolff, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Subclasses+of+external+adenosine+receptors.">Subclasses of external adenosine receptors.</a> Proc Natl Acad Sci. 77 (5), 2551-2554 (1980).</li><li>Lohse, M. J., Klotz, K. N., Lindenborn-Fotinos, J., Reddington, M., Schwabe, U., Olsson, R. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=8-Cyclopentyl-1,3-dipropylxanthine+(DPCPX)--a+selective+high+affinity+antagonist+radioligand+for+A1+adenosine+receptors.">8-Cyclopentyl-1,3-dipropylxanthine (DPCPX)--a selective high affinity antagonist radioligand for A1 adenosine receptors.</a> Naunyn Schmiedebergs Arch Pharmacol. 336 (2), 204-210 (1987).</li><li>Rybak, L. P., Whitworth, C., Scott, V., Weberg, A. D., Bhardwaj, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rat+as+a+potential+model+for+hearing+loss+in+biotinidase+deficiency.">Rat as a potential model for hearing loss in biotinidase deficiency.</a> Ann Otol Rhinol Laryngol. 100 (4), 294-300 (1991).</li><li>Mukherjea, D., 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=NOX3+NADPH+oxidase+couples+transient+receptor+potential+vanilloid+1+to+signal+transducer+and+activator+of+transcription+1-mediated+inflammation+and+hearing+loss.">NOX3 NADPH oxidase couples transient receptor potential vanilloid 1 to signal transducer and activator of transcription 1-mediated inflammation and hearing loss.</a> Antioxid Redox Signal. 14 (6), 999-1010 (2011).</li><li>Kaur, 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=Adenosine+A1+receptor+protects+against+cisplatin+ototoxicity+by+suppressing+the+NOX3/STAT1+inflammatory+pathway+in+the+cochlea.">Adenosine A1 receptor protects against cisplatin ototoxicity by suppressing the NOX3/STAT1 inflammatory pathway in the cochlea.</a> J Neurosci. 36 (14), 3962-3977 (2016).</li><li>Kaur, T., Mukherjea, D., Sheehan, K., Jajoo, S., Rybak, L. P., Ramkumar, V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Short+interfering+RNA+against+STAT1+attenuates+cisplatin-induced+ototoxicity+in+the+rat+by+suppressing+inflammation.">Short interfering RNA against STAT1 attenuates cisplatin-induced ototoxicity in the rat by suppressing inflammation.</a> Cell Death Dis. 2 (180), (2011).</li></ol>

Hiçbir çıkar çatışması ilan etti.

Aksi takdirde önemli sistemik yan sistemik yönetilen etkiler üretmek olabilir koklea yerelleştirilmiş teslim edilmesi, uyuşturucu ve diğer aracıları için trans-tympanic yönetim yolu sağlar. Bu yöntemi ilaç idaresi, sistemik yönlendirme yolu elde daha anlamlı olarak daha yüksek dozda uyuşturucu eylem siteye hızlı erişim sağlar. Burada sunulan ve yayınlanan sonuçları daha önce gösterdi [R] - N - fenil izopropil adenozin, trans-tympanic o Yönetimi (R-PIA) koklea sisplatin kaynak...

Periferik işitme sisteminin zarif sisplatin ve aminoglikosite antibiyotik gibi ilaçlar duyarlıdır. Sisplatin solid tümör, yumurtalık, testis ve baş gibi çeşitli tedavisinde yaygın olarak kullanılan bir kemoterapötik ajan olduğunu ve boyun kanserleri. Bu ilaç kullanımı ile deneyimli ototoksisite doz-sınırlayıcı olduğunu ve oldukça yaygın, hastaların % 75-100 etkileyen1ele. Carboplatin ve oxaliplatin'i, gibi diğer ilaçlar sisplatin2,3,4,5alternatif olarak ortaya çıkmıştır, ama bazı kanserler için onların yararlılığı sınırlıdır.
Erken çalışmalar Reaktif oksijen türleri (ROS) kritik rolü sisplatin ve aminoglikozitler tarafından üretilen ototoksisite arabuluculuk göstermiştir. Sonraki çalışmalarda NADPH oksidaz NOX3 izoformu ROS birincil kaynak koklea içinde ve sisplatin6,7tarafından aktif gösterdi. ROS tavizler nesil hücreler lider, kapasiteli tampon antioksidan lipid peroksidasyon hücresel zarları8arttı. Ayrıca, sisplatin yüksek derecede toksik aldehid 4-hydroxynonenal (4-HNE), hücre ölüm9,10başlatıcı oluşturmak hidroksil radikalleri üretimi artar. Bu bulgulara dayanarak, birkaç antioksidanlar sisplatin ototoksisite tedavisi için inceledik. Bu N-asetil sistein (NAC), sodyum thiosulfate (STS), amifostine ve D-metionin içerir. Ancak, antioksidan tedavinin asıl ilgilendiği temel konu bu antioksidanlar sistemik11 sisplatin thiol gruplar halinde antioksidan molekülleri ile etkileşimi aracılığıyla yönetilen zaman sisplatin kemoterapi etkinliğini azaltabilir olduğunu.
Antioksidan tedavisi ile bu sorunların içinde görüş-in bu çalışmanın hedefi, antioksidanlar ve diğer uyuşturucular işitme kaybı azaltmak için koklea teslim etme trans-tympanic rota incelemek için oldu. Uyuşturucu ve kısa (SI) RNA, aşağıda açıklanan engel trans-tympanic güzergahı özellikle umut verici görünüyor.

<table><tbody><tr><td>Ketathesia (100 mg/ml) 10 ml</td><td>Henry Schein</td><td>56344</td><td>Controlled substance&amp;nbsp;</td></tr><tr><td>AnaSed Injection/Xylazine (20 mg/ml) 20 ml</td><td>Henry Schein</td><td>33197</td><td></td></tr><tr><td>2.5 mm disposable ear specula</td><td>Welch Allyn</td><td>52432</td><td></td></tr><tr><td>Surgical Scope</td><td>Zeiss</td><td></td><td></td></tr><tr><td>29 G X 1/2 insulin syringe</td><td>Fisher Scientific</td><td>14-841-32&amp;nbsp;</td><td>Can be purchased through other vendors</td></tr><tr><td>cis-Diammineplatinum(II) dichloride</td><td>Sigma Aldrich</td><td>P4394</td><td>TOXIC - wear proper PPE</td></tr><tr><td>Harvard 50-7103 Homeothermic Blanket Control Unit</td><td>Harvard Apparatus</td><td>Series 863</td><td></td></tr><tr><td>Excel International 21 G X 3/4 butterfly needle</td><td>Fisher</td><td>14-840-34&amp;nbsp;</td><td>Can be purchased through other vendors</td></tr><tr><td>BSP Single Speed Syringe Pump</td><td>Brain Tree Sci, Inc</td><td>BSP-99</td><td></td></tr><tr><td>Pulse Sound Measurement System</td><td>Bruel &amp;amp; Kjaer</td><td>Pulse 13 software</td><td></td></tr><tr><td>High-Frequency Module</td><td>Bruel &amp;amp; Kjaer</td><td>3560C</td><td></td></tr><tr><td>1/8&amp;Prime; Pressure-field Microphone &amp;mdash;-Type 4138</td><td>Bruel &amp;amp; Kjaer</td><td>bp2030</td><td></td></tr><tr><td>High Frequency Transducer</td><td>Intelligent Hearing System</td><td>M014600</td><td></td></tr><tr><td>Opti-Amp Power Transmitter</td><td>Intelligent Hearing System</td><td>M013010P</td><td></td></tr><tr><td>SmartEP ABR System</td><td>Intelligent Hearing System</td><td>M011110</td><td></td></tr><tr><td>Disposable Subdermal EEG Electrodes</td><td>CareFusion</td><td>019-409700</td><td></td></tr><tr><td>16% Formaldehyde, Methanol-free</td><td>Fisher Scientific</td><td>28908</td><td>TOXIC - wear proper PPE&amp;nbsp;</td></tr><tr><td>7 mL Borosilicate Glass Scintillation Vial</td><td>Fisher Scientific</td><td>03-337-26</td><td>Can be purchased through other vendors</td></tr><tr><td>EDTA</td><td>Fisher Scientific</td><td>BP118-500</td><td>Can be purchased through other vendors</td></tr><tr><td>Sucrose</td><td>Fisher Scientific</td><td>S5-500</td><td>Can be purchased through other vendors</td></tr><tr><td>Tissue Plus OCT Compound</td><td>Fisher Scientific</td><td>4585</td><td></td></tr><tr><td>CryoMolds (15 mm x 15 mm x 5mm)</td><td>Fisher Scientific</td><td>22-363-553</td><td>Can be purchased through other vendors</td></tr><tr><td>Microscope Slides (25mm x 75mm)</td><td>MidSci</td><td>1354W</td><td>Can be purchased through other vendors</td></tr><tr><td>Coverslips (22 x 22 x 1)</td><td>Fisher Scientific</td><td>12-542-B</td><td>Can be purchased through other vendors</td></tr><tr><td>Poly-L-Lysine Solution (0.01%)</td><td>EMD Millipore</td><td>A-005-C</td><td>Can be purchased through other vendors</td></tr><tr><td>HM525 NX Cryostat</td><td>Thermo Fischer Scientific</td><td>956640</td><td></td></tr><tr><td>MX35 Premier Disposable Low-Profile Microtome Blades</td><td>Thermo Fischer Scientific</td><td>3052835</td><td></td></tr><tr><td>Wheaton&amp;trade;&amp;nbsp;Glass 20-Slide Staining Dish with Removable Rack</td><td>Fisher Scientific</td><td>08-812</td><td></td></tr><tr><td>Super Pap Pen Liquid Blocker</td><td>Ted Pella, Inc.</td><td>22309</td><td></td></tr><tr><td>Normal Donkey Serum</td><td>Jackson Immuno Research</td><td>017-000-121</td><td>Can be purchased through other vendors</td></tr><tr><td>TritonX-100</td><td>Acros</td><td>21568</td><td>Can be purchased through other vendors</td></tr><tr><td>BSA</td><td>Sigma Aldrich</td><td>A7906</td><td>Can be purchased through other vendors</td></tr><tr><td>Phospho-Stat1 (Ser727) antibody</td><td>Cell Signaling</td><td>9177</td><td></td></tr><tr><td>VR1 Antibody (C-15)</td><td>Santa Cruz</td><td>sc-12503</td><td></td></tr><tr><td>DyLight 488 Donkey anti Rabbit</td><td>Jackson Immuno Research</td><td>711-485-152</td><td>Discontinued</td></tr><tr><td>DyLight 488 Donkey anti Goat</td><td>Jackson Immuno Research</td><td>705-485-003</td><td>Discontinued</td></tr><tr><td>Rhodamine (TRTIC) Donkey anti Rabbit</td><td>Jackson Immuno Research</td><td>711-025-152</td><td>Discontinued</td></tr><tr><td>ProLong&amp;reg; Diamond Antifade Mountant w/ DAPI</td><td>Thermo Fisher</td><td>P36971</td><td></td></tr><tr><td>(&amp;minus;)-N6-(2-Phenylisopropyl)adenosine</td><td>Sigma Aldrich</td><td>P4532</td><td></td></tr><tr><td>8-Cyclopentyl-1,3-dipropylxanthine</td><td>Sigma Aldrich</td><td>C101</td><td></td></tr><tr><td>siRNA pSTAT1</td><td>Qiagen</td><td>Custome Made</td><td>Kaur et al. 2011&lt;sup&gt;20&lt;/sup&gt;</td></tr><tr><td>siRNA NOX3</td><td>Qiagen</td><td>Custome Made</td><td>Kaur et al. 2011&lt;sup&gt;20&lt;/sup&gt;</td></tr><tr><td>Scrambled Negative Control siRNA</td><td>Qiagen</td><td>1022076</td><td>Kaur et al. 2011&lt;sup&gt;20&lt;/sup&gt;</td></tr></tbody></table>

trans-tympanic drug delivery for the treatment of ototoxicity

Sistemik yönetim ototoksisite ilaçla tedavi etmek için koruyucu ajanlar bu koruyucu ajanlar ile birincil ilaçların etkinliğini kemoterapötik engelleyebilir imkanı ile sınırlıdır. Bu, özellikle antikanser eylemlerini işitme kaybına karşı yeterli koruma sağlamak Antioksidanlar tarafından zayıflatılmış uyuşturucu sisplatin için geçerlidir. Diğer mevcut ya da potansiyel otoprotective temsilcileri benzer bir sorun, sistemik yönetilen doğuracak. Koklea doğrudan çeşitli biyolojik madde veya koruyucu uygulamayı yerel olarak sınırlı sistemik yan etkileri ile bu ajanların yüksek düzeyleri için izin vermez. Bu raporda, çeşitli uyuşturucu veya biyolojik reaktifler teslimat için temel bilim araştırma koklea geliştirmek ve otoprotective ajanlar kliniklerde kullanımını yönlendiren basit bir yol sağlar koklea, trans-tympanic bir yöntemi göstermektedir. Bu rapor trans-tympanic ilaç dağıtım yöntemi ayrıntıları ve nasıl bu tekniği başarıyla deneysel hayvanlarda sisplatin ototoksisite tedavisinde kullanılmaya başlanmıştır kullanım örnekleri sağlar.

ABR yanıt-e doğru üç gün aşağıdaki sisplatin yönetim önemli bir ayrıcalık eşikleri gösterdi de, fareler ölçülür. Bu eşikleri yükselmesine önemli ölçüde azaltılmış trans-tympanic [R] - N - phenylisopropyladenosine ile yönetilen Sıçanlarda (R-PIA), adenozin bir1 reseptör agonist15, sisplatin önce. Reylem özgüllük-1 reseptör gösterdi bu 8-Cyclopentyl-1,3-dipropylxanthine tarafından ...

Watch this Scientific Journal Video about Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity at JoVE.com

Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity

Biz bir teknik trans-tympanic rota üzerinden uyuşturucu yerelleştirilmiş yönetim koklea içine için mevcut. Bu rota üzerinden ilaç dağıtım gibi sisplatin kemoterapi ilaçların anti-kanser etkinliği ile müdahale olmaz.

Trans-Tympanic ilaç dağıtım ototoksisite tedavisi için

The systemic administration of protective agents to treat drug-induced ototoxicity is limited by the possibility that these protective agents could ...

trans-tympanic-drug-delivery-for-the-treatment-of-ototoxicity

Research

JoVE Journal

Medicine

9.3K Görüntüleme.  Southern Illinois University School of Medicine. Biz bir teknik trans-tympanic rota üzerinden uyuşturucu yerelleştirilmiş yönetim koklea içine için mevcut. Bu rota üzerinden ilaç dağıtım gibi sisplatin kemoterapi ilaçların anti-kanser etkinliği ile müdahale olmaz.

Video: Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity

Thermal Ablation for the Treatment of Abdominal Tumors

Percutaneous thermal ablation is an emerging treatment option for many tumors of the abdomen not amenable to conventional treatments. During a thermal ablation procedure, a thin applicator is guided into the target tumor under imaging guidance. Energy is then applied to the tissue until temperatures rise to cytotoxic levels (50-60 &deg;C). Various energy sources are available to heat biological tissues, including radiofrequency (RF) electrical current, microwaves, laser light and ultrasonic waves. Of these, RF and microwave ablation are most commonly used worldwide.
During RF ablation, alternating electrical current (~500 kHz) produces resistive heating around the interstitial electrode. Skin surface electrodes (ground pads) are used to complete the electrical circuit. RF ablation has been in use for nearly 20 years, with good results for local tumor control, extended survival and low complication rates1,2. Recent studies suggest RF ablation may be a first-line treatment option for small hepatocellular carcinoma and renal-cell carcinoma3-5. However, RF heating is hampered by local blood flow and high electrical impedance tissues (eg, lung, bone, desiccated or charred tissue)6,7. Microwaves may alleviate some of these problems by producing faster, volumetric heating8-10. To create larger or conformal ablations, multiple microwave antennas can be used simultaneously while RF electrodes require sequential operation, which limits their efficiency. Early experiences with microwave systems suggest efficacy and safety similar to, or better than RF devices11-13.
Alternatively, cryoablation freezes the target tissues to lethal levels (-20 to -40 &deg;C). Percutaneous cryoablation has been shown to be effective against RCC and many metastatic tumors, particularly colorectal cancer, in the liver14-16. Cryoablation may also be associated with less post-procedure pain and faster recovery for some indications17. Cryoablation is often contraindicated for primary liver cancer due to underlying coagulopathy and associated bleeding risks frequently seen in cirrhotic patients. In addition, sudden release of tumor cellular contents when the frozen tissue thaws can lead to a potentially serious condition known as cryoshock 16.
Thermal tumor ablation can be performed at open surgery, laparoscopy or using a percutaneous approach. When performed percutaneously, the ablation procedure relies on imaging for diagnosis, planning, applicator guidance, treatment monitoring and follow-up. Ultrasound is the most popular modality for guidance and treatment monitoring worldwide, but computed tomography (CT) and magnetic resonance imaging (MRI) are commonly used as well. Contrast-enhanced CT or MRI are typically employed for diagnosis and follow-up imaging.

A thermal tumor ablation procedure is described. The entire procedure is detailed, including pretreatment planning and imaging studies, anesthesia, adjuvant techniques to facilitate a percutaneous approach, imaging guidance of the ablation device to the tumor, thermal treatment, post-treatment care and follow-up.

Karın Tümörler Tedavi için Termal Ablasyon

Percutaneous thermal ablation is an emerging treatment option for many tumors of the abdomen not amenable to conventional treatments. During a thermal ...

Tıp

Canalostomy As a Surgical Approach to Local Drug Delivery into the Inner Ears of Adult and Neonatal Mice

Local delivery of therapeutic drugs into the inner ear is a promising therapy for inner ear diseases. Injection through semicircular canals (canalostomy) has been shown to be a useful approach to local drug delivery into the inner ear. The goal of this article is to describe, in detail, the surgical techniques involved in canalostomy in both adult and neonatal mice. As indicated by fast-green dye and adeno-associated virus serotype 8 with the green fluorescent protein gene, the canalostomy facilitated broad distribution of injected reagents in the cochlea and vestibular end-organs with minimal damage to hearing and vestibular function. The surgery was successfully implemented in both adult and neonatal mice; indeed, multiple surgeries could be performed if required. In conclusion, canalostomy is an effective and safe approach to drug delivery into the inner ears of adult and neonatal mice and may be used to treat human inner ear diseases in the future.

Here we describe canalostomy procedure which allows local drug delivery into the inner ears of adult and neonatal mice through the semicircular canal with minimum damage to hearing and vestibular function. This method can be used to inoculate viral vectors, pharmaceuticals, and small molecules into the mouse inner ear.

Canalostomy yerel ilaç dağıtım yetişkin ve Neonatal farelerin iç kulaklarına bir cerrahi yaklaşım olarak

Local delivery of therapeutic drugs into the inner ear is a promising therapy for inner ear diseases. Injection through semicircular canals (canalostomy) ...

Genetik

Optogenetic Stimulation of the Auditory Nerve

Direct electrical stimulation of spiral ganglion neurons (SGNs) by cochlear implants (CIs) enables open speech comprehension in the majority of implanted deaf subjects1-6. Nonetheless, sound coding with current CIs has poor frequency and intensity resolution due to broad current spread from each electrode contact activating a large number of SGNs along the tonotopic axis of the cochlea7-9. Optical stimulation is proposed as an alternative to electrical stimulation that promises spatially more confined activation of SGNs and, hence, higher frequency resolution of coding. In recent years, direct infrared illumination of&#160;the cochlea has been used to evoke responses in the auditory nerve10. Nevertheless it requires higher energies than electrical stimulation10,11 and uncertainty remains as to the underlying mechanism12. Here we describe a method based on optogenetics to stimulate SGNs with low intensity blue light, using transgenic mice with neuronal expression of channelrhodopsin 2 (ChR2)13 or virus-mediated expression of the ChR2-variant CatCh14. We used micro-light emitting diodes (&#181;LEDs) and fiber-coupled lasers to stimulate ChR2-expressing SGNs through a small artificial opening (cochleostomy) or the round window. We assayed the responses by scalp recordings of light-evoked potentials (optogenetic auditory brainstem response: oABR) or by microelectrode recordings from the auditory pathway and compared them with acoustic and electrical stimulation.

Cochlear implants (CIs) enable hearing by direct electrical stimulation of the auditory nerve. However, poor frequency and intensity resolution limits the quality of hearing with CIs. Here we describe optogenetic stimulation of the auditory nerve in mice as an alternative strategy for auditory research and developing future CIs.

İşitsel Sinir optogenetic uyarılması

Direct electrical stimulation of spiral ganglion neurons (SGNs) by cochlear implants (CIs) enables open speech comprehension in the majority of implanted ...

Nörobilim

Surgical Method for Virally Mediated Gene Delivery to the Mouse Inner Ear through the Round Window Membrane

Gene therapy, used to achieve functional recovery from sensorineural deafness, promises to grant better understanding of the underlying molecular and genetic mechanisms that contribute to hearing loss. Introduction of vectors into the inner ear must be done in a way that widely distributes the agent throughout the cochlea while minimizing injury to the existing structures. This manuscript describes a post-auricular surgical approach that can be used for mouse cochlear therapy using molecular, pharmacologic, and viral delivery to mice postnatal day 10 and older via the round window membrane (RWM). This surgical approach enables rapid and direct delivery into the scala tympani while minimizing blood loss and avoiding animal mortality. This technique involves negligible or no damage to essential structures of the inner and middle ear as well as neck muscles while wholly preserving hearing. To demonstrate the efficacy of this surgical technique, the vesicular glutamate transporter 3 knockout (VGLUT3 KO) mice will be used as an example of a mouse model of congenital deafness that recovers hearing after delivery of VGLUT3 to the inner ear using an adeno-associated virus (AAV-1).

The described post-auricular surgical approach allows rapid and direct delivery into the mouse cochlear scala tympani while minimizing blood loss and animal mortality. This method can be used for cochlear therapy using molecular, pharmacologic and viral delivery to postnatal mice through the round window membrane.

Yuvarlak Pencere Membran aracılığıyla Fare İç Kulak için virally ve Gen Teslimat Cerrahi Yöntemi

Gene therapy, used to achieve functional recovery from sensorineural deafness, promises to grant better understanding of the underlying molecular and ...

The Mouse Round-window Approach for Ototoxic Agent Delivery: A Rapid and Reliable Technique for Inducing Cochlear Cell Degeneration

Investigators have utilized a wide array of animal models and investigative techniques to study the mammalian auditory system. Much of the basic research involving the cochlea and its associated neural pathways entails exposure of model cochleae to a variety of ototoxic agents. This allows investigators to study the effects of targeted damage to cochlear structures, and in some cases, the self-repair or regeneration of those structures. Various techniques exist for delivery of ototoxic agents to the cochlea. When selecting a particular technique, investigators must consider a number of factors, including the induction of inadvertent systemic toxicity, the amount of cochlear damage produced by the surgical procedure itself, the type of lesion desired, animal survivability, and reproducibility/reliability of results. Currently established techniques include parenteral injection, intra-peritoneal injection, trans-tympanic injection, endolymphatic sac injection, and cochleostomy with perilymphatic perfusion. Each of these methods has been successfully utilized and is well described in the literature; yet, each has various shortcomings. Here, we present a technique for topical application of ototoxic agents directly to the round window niche. This technique is non-invasive to inner ear structures, produces rapid onset of reliably targeted lesions, avoids systemic toxicity, and allows for an intra-animal control (the contra-lateral ear). Results stemming from this approach have helped deeper understanding of auditory pathophysiology, cochlear cell degeneration, and regenerative capacity in response to an acute injury. Future investigations may use this method to conduct interventional studies involving gene therapy and stem cell transplantation to combat hearing loss.

Various methods exist for introducing ototoxic agents to the cochleae of animal models. Presented is a surgical protocol for delivery of ototoxic agents to the round window niche. The procedure is reliable, creates targeted intra-cochlear lesions, and avoids mechanical damage to the microarchitecture. Examination of cochlear self-repair/regeneration is possible.

Koklear Hücre Dejenerasyonu Inducing için hızlı ve Güvenilir Teknik: Ototoksik Ajan Teslimat için Fare Yuvarlak pencere Yaklaşımı

Investigators have utilized a wide array of animal models and investigative techniques to study the mammalian auditory system. Much of the basic research ...

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

Hearing research has long been facilitated by rodent models, although in some diseases, human symptoms cannot be recapitulated. The common marmoset (Callithrix jacchus) is a small, easy-to-handle New World monkey which has a similar anatomy of the temporal bone, including the middle ear ossicular chains and inner ear to humans, than in comparison with that of rodents. Here, we report a reproducible, safe, and rational surgical approach to the cochlear round window niche for the drug delivery to the inner ear of the common marmoset. We adopted posterior tympanotomy, a procedure used clinically in human surgery, to avoid manipulation of the tympanic membrane that may cause conductive hearing loss. This surgical procedure did not lead to any significant hearing loss. This approach was possible due to the large bulla structure of the common marmoset, although the lateral semicircular canal and vertical portion of the facial nerve should be carefully considered. This surgical method allows us to perform the safe and accurate administration of drugs without hearing loss, which is of great importance in obtaining pre-clinical proof of concept for translational research.

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

We report a surgical method to administrate drugs to the inner ear of a non-human primate, the common marmoset (Callithrix jacchus), via the round window membrane.

Bir insan olmayan primatların ortak Marmoset (Callithrix jacchus) iç kulak ilaçlara Yönetim için bir cerrahi prosedür

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

Endaural Endoscopic Atticoantrotomy (Retrograde Mastoidectomy) using a Constant Suction Bone-drilling Technique

Endoscopic middle ear surgery is a widely employed minimally invasive surgical technique to address middle ear and mastoid pathology. Bone drilling is the main technical challenge of endoscopic middle ear surgery. The accompanying video describes the detailed protocol of a constant-suction bone-drilling technique and the procedure of endaural exclusive endoscopic atticoantrotomy (retrograde mastoidectomy) using this technique. The main components of this bone-drilling technique include a soft and flexible suction tube, which is placed into the tympanic cavity to provide constant suction, and a soft sleeve, which is wrapped around the drill shaft to prevent the high-speed rotating shaft from damaging the lens of the endoscope. With these simple modifications, the traditional otological electrodrill can be used for drilling a tiny endaural incision in endoscopic middle ear surgery. Based on this bone-drilling technique, endaural endoscopic atticoantrotomy (retrograde mastoidectomy) can be successfully established for the removal of various amounts of bone, depending on the extent of the lesion. The short-term postoperative outcome seems promising.

Endaural Endoscopic Atticoantrotomy Retrograde Mastoidectomy using a Constant Suction Bone-drilling Technique

In this paper, we present the protocol and short-term outcomes of endaural exclusive endoscopic atticoantrotomy using a constant suction bone-drilling technique.

Sürekli Emme Kemik Delme Tekniği Kullanılarak Endaural Endoskopik Attikoantrotomi (Retrograd Mastoidektomi)

Endoscopic middle ear surgery is a widely employed minimally invasive surgical technique to address middle ear and mastoid pathology. Bone drilling is the ...

A Comparative Study of Drug Delivery Methods Targeted to the Mouse Inner Ear: Bullostomy Versus Transtympanic Injection

We present two minimally invasive microsurgical techniques in rodents for specific drug delivery into the middle ear so that it may reach the inner ear. The first procedure consists of perforation of the tympanic bulla, termed bullostomy; the second one is a transtympanic injection. Both emulate human clinical intratympanic procedures.
Chitosan-glycerophosphate (CGP) and Ringer&#180;s Lactate buffer (RL) were used as biocompatible vehicles for local drug delivery. CGP is a nontoxic biodegradable polymer widely used in pharmaceutical applications. It is a viscous liquid at RT&#160;but it congeals to a semi solid phase at body temperature. RL is an isotonic solution used for intravenous administrations in humans. A small volume of this vehicle is precisely placed on the Round Window (RW) niche by means of a bullostomy. A transtympanic injection fills the middle ear and allows less control but broader access to the inner ear.
The safety profiles of both techniques were studied and compared by using functional and morphological tests. Hearing was evaluated by registering the Auditory Brainstem Response (ABR) before and several times after microsurgery. The cytoarchitecture and preservation level of cochlear structures were studied by conventional histological techniques in paraformaldehyde-fixed and decalcified cochlear samples. In parallel, unfixed cochlear samples were taken and immediately frozen to analyze gene expression profiles of inflammatory markers by quantitative Reverse Transcriptase Polymerase Chain Reaction (qRT-PCR).
Both procedures are suitable as drug delivery methods into the mouse middle ear, although transtympanic injection proved to be less invasive compared to bullostomy.

A Comparative Study of Drug Delivery Methods Targeted to the Mouse Inner Ear: Bullostomy Versus Transtympanic Injection

Two microsurgery approaches for local drug delivery to the inner ear are described here and compared in terms of impact on hearing parameters, cochlear cytoarchitecture and expression of inflammatory markers.

Fare İç Kulak Hedefli İlaç Dağıtım Yöntemleri Karşılaştırmalı İncelemesi: Bullostomy<em&gt; Karşı</em&gt; Transtimpanik Enjeksiyon

We present two minimally invasive microsurgical techniques in rodents for specific drug delivery into the middle ear so that it may reach the inner ear. ...

Biyoloji

<meta charset="utf8"></head><body>Elektrik-Akustik Stimülasyonda Uzun Elektrotlarla İşitmenin Korunması

Enhanced Cochlear Coverage and Hearing Preservation in High-Frequency Hearing Loss via Electric Acoustic Stimulation with Longer Electrode

Electric-acoustic stimulation (EAS) is a promising treatment to improve hearing ability in patients with high-frequency hearing loss (HL). In EAS surgeries, shorter electrodes have been preferred to avoid the presence of an electrode covering the residual hearing region. However, our earlier studies showed that EAS with longer electrodes (28 mm) could preserve acoustic hearing. Additionally, we reported that the hearing preservation (HP) scores were independent of the length of the inserted electrodes, consistent with the systematic review. As most EAS patients gradually lose residual hearing over time due to the natural course of HL, in these cases, providing broader cochlear coverage using longer electrodes was beneficial toward better place-pitch matching. In addition to preparing for the deterioration in&#160;hearing in&#160;the future, EAS with longer electrodes could offer various types of map strategies. Herein, we show the pre-, intra-, and post-procedures for EAS surgery. Appropriate preoperative evaluation, less invasive surgery, flexible lateral-wall electrodes, and steroid administration resulted in good HP following EAS with longer electrodes.

<meta charset="utf8"></head><body>Yazar İncelemesi: Gelişmiş Koklear Kapsama Alanı ve İşitmenin Korunması için Uzun Elektrotlarla EAS'ı Optimize Etme

Electric acoustic stimulation (EAS) with longer electrodes can offer broader cochlear coverage and various types of maps in cases of high-frequency hearing loss. Combining less invasive surgery, flexible lateral-wall electrodes, and steroid administration permits deeper insertion with little or no surgical trauma, resulting in good preservation of hearing.

Trans-Tympanic ilaç dağıtım ototoksisite tedavisi için

Özet

Daha Fazla Video Keşfet