References on the Administration of Agents to the Ear Using ALZET^® Osmotic Pumps

Q0453 Agterberg,M.J.H., Versnel,H., van Dijk,L.M., de Groot,J.C.M.J., Klis,S.F.L. Enhanced Survival of Spiral Ganglion Cells After Cessation of Treatment with Brain-Derived Neurotrophic Factor in Deafened Guinea Pigs. JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY 2009; 10(-3-):355-367. >>> Brain-derived neurotrophic factor; BSA; Ear (cochlea); Guinea pig; 2004; 4 weeks; Controls were untreated; animal info (albino, female, 250-350 g); pump connected to Cochlear (R) electrode array; tissue perfusion (cochlea).

P9796 Fransson,A., Jaerlebark,L.E., Ulfendahl,M. In Vivo Infusion of UTP and Uridine to the Deafened Guinea Pig Inner Ear: Effects on Response Thresholds and Neural Survival. Journal of Neuroscience Research 2009; 87(-7-):1712-1717. >>> Uridine triphosphate; uridine; Ear (cochlea); Guinea-pig; 2002; 25 days; Controls received mp w/ artificial perilymph; pumps replaced on day 13; animal info (pigmented, 280-440 g); tissue perfusion.

Q0333 Nguyen,Y., Couloigner,V., Rudic,M., Grayeli,A.B., Ferrary,E., Sterkers,O. An animal model of cochlear implantation with an intracochlear fluid delivery system. Acta Oto-laryngologica 2009; 129(-11-):1153-1159. >>> Saline; Ear (cochlea); Guinea pig; 1007D; ; Controls received pump without electrode implant; animal info (albino, male, 3 to 7 months old, 290-1030 g.); good methods pg 1154; post op. care (enrofloxacine); "the pump was fixed subcutaneously between the scapulae using a vicryl 3/0 suture (Ethicon)" pg 1154; image of pump-electrode deive, Fig. 1; tissue perfusion (cochlea).

P9844 Orita,H., Shimogori,H., Yamashita,H. Unilateral intra-perilymphatic infusion of substance P enhances ipsilateral vestibulo-ocular reflex gains in the sinusoidal rotation test. Neuroscience Letters 2009; 449(-3-):207-210. >>> Substance P; neurokinin-1 receptor antagonist; Ear (round window); Guinea-pig; 2002; ; Post op. care (piperacillin sodium); animal info (Hartley); pump was connected to a PE catheter filled with artificial perilymph for a 12-hour delayed infusion; tissue perfusion (round window).

P9515 Scheper,V., Paasche,G., Miller,J.M., Warnecke,A., Berkingali,N., Lenarz,T., Stoever,T. Effects of Delayed Treatment With Combined GDNF and Continuous Electrical Stimulation on Spiral Ganglion Cell Survival in Deafened Guinea Pigs. Journal of Neuroscience Research 2009; 87(-6-):1389-1399. >>> Glial-derived neurotrophic factor; Ear (cochlea); Guinea-pig; 2002; 48 days; Controls received mp w/artificial perilymph; tissue perfusion (cochlea); long-term study; pumps replaced after 13 days; good methods (pg. 1391); animal info (male, pigmented, 250-450 g.); pumps primed; image of pump and electrode cannula device used on fig. 1.

P9239 Harris,J.A., Iguchi,F., Seidl,A.H., Lurie,D.I., Rubel,E.W. Afferent Deprivation Elicits a Transcriptional Response Associated with Neuronal Survival after a Critical Period in the Mouse Cochlear Nucleus. Journal of Neuroscience 2008; 28(-43-):10990-11002. >>> Tetrodotoxin; Citrate buffer; Ear (round window niche); Mice; 1003D; 24 hours; Controls received mp w/ saline or no treatment to contralateral side; tissue perfusion (round window niche); comparison of cochlear removal vs. mp; animal info (male, female, C57BL/6J, 21 days old).

P9760 Keithley,E.M., Wang,X.B., Barkdull,G.C. Tumor necrosis factor alpha can induce recruitment of inflammatory cells to the cochlea. OTOLOGY&NEUROTOLOGY 2008; 29(-6-):854-859. >>> Tumor necrosis factor-alpha; Ear (cochlea); Guinea-pig; 2001; 2-4 days; Controls received mp w/vehicle; animal info (Hartley albino); tissue perfusion.

P9306 Panford-Walsh,R., Singer,W., Ruettiger,L., Hadjab,S., Tan,J., Geisler,H.S., Zimmermann,U., Koepschall,I., Rohbock,K., Vieljans,A., Oestreicher,E., Knipper,M. Midazolam reverses salicylate-induced changes in brain-derived neurotrophic factor and Arg3.1 expression: Implications for tinnitus perception and auditory plasticity. MOLECULAR PHARMACOLOGY 2008; 74(-3-):595-604. >>> Midazolam; Ear (round window niche); Rat; 2001; 7 days; Controls received mp w/ artificial perilymph; comparison of systemic injections vs. mp; animal info (female, Wistar, 200-300 g., cochlear trauma); behavioral testing (tinnitus perception via sound/reward); tissue perfusion (round window niche).

P9224 Reyes,J.H., O'Shea,K.S., Wys,N.L., Velkey,J.M., Prieskorn,D.M., Wesolowski,K., Miller,J.M., Altschuler,R.A. Glutamatergic Neuronal Differentiation of Mouse Embryonic Stem Cells after Transient Expression of Neurogenin 1 and Treatment with BDNF and GDNF: In Vitro and In Vivo Studies. Journal of Neuroscience 2008; 28(-48-):12622-12631. >>> Doxycycline; brain-derived neurotrophic factor; glial cell line-derived neurotrophic factor; Ear (scala tympani); Guinea-pig; 2002; 27 days; Controls received no treatment to contralateral ear; pumps replaced; peptides; tissue perfusion (scala tympani); animal info (NIH strain, 275-315 g., deafened); cannula and catheter contained doxycycline, mp contained BDNF/GDNF (delayed delivery) to follow, thus providing 2 days Dox, 25 days BDNF/GDNF.

P9218 Shepherd,R.K., Coco,A., Epp,S.B. Neurotrophins and electrical stimulation for protection and repair of spiral ganglion neurons following sensorineural hearing loss. Hearing Research 2008; 242(-1-2-):100-109. >>> Brain-derived neurotrophic factor, recomb. human; Ringer's solution; albumin, guinea pig; Ear (scala tympani); Guinea-pig; 2004; 4 weeks; Controls received no treatment to contralateral cochlea; functionality of mp verified by residual volume and intact connections; peptides; post op. care (Carprofen, Baytril); tissue perfusion (scala tympani); animal info (pigmented, 400-844 g., kanamycin/furosemide deafened).

P9051 Song,B.N., Li,Y.X., Han,D.M. Effects of delayed brain-derived neurotrophic factor application on cochlear pathology and auditory physiology in rats. Chinese Medical Journal 2008; 121(-13-):1189-1196. >>> Brain-derived neurotrophic factor, recomb. human; Albumin, rat; Ringer's solution; Ear (cochlea); Rat; 2004; 28 days; Controls received mp w/ vehicle; animal info (male, albino, Sprague Dawley, 10-12 wks old, 220-250 g.); tissue perfusion (cochlea); functionality of mp verified by residual volume; good methods pg. 1191; pumps were primed in sterile saline at 37 degree Celsius for 48 hours; 1-cm len.

R0266 Swan,E.E.L., Mescher,M.J., Sewell,W.F., Tao,S.L., Borenstein,J.I. Inner ear drug delivery for auditory applications. Advanced Drug Delivery Reviews 2008; 60(-15-):1583-1599. >>> Cisplatin; Sodium thiosulfate; Brain-derived neurotrophic factor; Fibroblast growth factor; D-JNKI-1; BN82270; Tetrodotoxin; Perilymph, artificial; Dexamethasone; Methylprednisone; Caroverine; Methionine, D-; Thiourea; Liposome, cationic; Neomycin; SC; Ear (round window membrane); Ear (cochlea); Ear (scala tympani); Ear; Guinea pig; 3, 7, 14, 28 days; Gene therapy; peptdies; no stress; enzyme inhibitor (peroxidase); stress/adverse reaction (see pg 1593) "Ref #161 found local trauma and inflammatory responses"; tissue perfusion (scala tympani, cochlea, round window membrane); comparison of middle ear injections vs. mp; Review, see pgs. 1587 - 1589, 1591, 1593 - 1595, refs #49, 50, 60, 63, 72, 75, 102, 104,180, 181, 194-201,.

P9292 Vivero,R.J., Joseph,D.E., Angeli,S., He,J., Chen,S.B., Eshraghi,A.A., Balkany,T.J., Van de Water,T.R. Dexamethasone Base Conserves Hearing from Electrode Trauma-Induced Hearing Loss. Laryngoscope 2008; 118(-11-):2028-2035. >>> Dexamethasone base; Perilymph, artificial; Ear (scala tympani); Guinea-pig; 2001; 8 days; Controls received mp w/ vehicle; replacement therapy (cochleostomy); tissue perfusion (scala tympani); animal info (pigmented, 250-300 g.).

P8068 Cafaro,J., Lee,G.S., Stone,J.S. Atoh1 expression defines activated progenitors and differentiating hair cells during avian hair cell regeneration. Developmental Dynamics 2007; 236(-1-):156-170. >>> Uridine, bromodeoxy-; PBS; Ear (perilymphatic fluid); Bird (chicken); 2002; 8 days; No stress (see p.167); Alzet brain infusion kit used; animal info (White Legorn, 5-10 days old).

P8429 Frederiksen,B.L., Caye-Thomasen,P., Lund,S.P., Wagner,N., Asal,K., Olsen,N.V., Thomsen,J. Does erythropoietin augment noise induced hearing loss?. Hearing Research 2007; 223(-1-2-):129-137. >>> Erythropoietin; Ear (round window); Guinea-Pig; 1007D; 1 week; Controls received mp w/ saline; replacement therapy (noise-induced hearing impairment); comparison of acute admin. vs. mp; peptides; animal info (male, Dunkin-Hartley); tissue perfusion (round window); mp primed 6 hours in 37 Celsius saline; correct catheter placement confirmed.

P8724 Hori,R., Nakagawa,T., Sakamoto,T., Matsuoka,Y., Takebayashi,S., Ito,J. Pharmacological inhibition of Notch signaling in the mature guinea pig cochlea. NeuroReport 2007; 18(-18-):1911-1914. >>> MDL 28170; DMSO; PBS; Ear (cochlea); Guinea-pig; 1002; 14 days; Tissue perfusion (cochlea); enzyme inhibitor (gamma secretase); peptides; animal info (Hartley strain, 350-400g); MDL 28170 is a gamma-secretase inhibitor; 0.3% DMSO used; "a silicon tube (180 micron OD) connected to a micro-osmotic minipump...".

P8402 Maruyama,J., Yamagata,T., Ulfendahl,M., Bredberg,G., Altschuler,R.A., Miller,J.M. Effects of antioxidants on auditory nerve function and survival in deafened guinea pigs. NEUROBIOLOGY OF DISEASE 2007; 25(-2-):309-318. >>> Trolox; neomycin; ascorbic acid; Perilymph, artificial; sodium bicarbonate; Ear (cochlea); Guinea-Pig; 2002; 26 days; Controls received mp w/ vehicle; pumps replaced after 14 days; post op. care (doxycycline); animal info (male, pigmented, 250-400g., neomycin deafening); cannula primed with 10% neomycin solution followed by a small air bubble spacer to allow neomycin infusion for first 2 days; trolox, a vitamin F analogue, and ascorbic acid delivered together in 1 mp; tissue perfusion (cochlea).

P8661 Miller,J.M., Le Prell,C.G., Prieskorn,D.M., Wys,N.L., Altschuler,R.A. Delayed neurotrophin treatment following deafness rescues spiral ganglion cells from death and promotes regrowth of auditory nerve peripheral processes: Effects of brain-derived neurotrophic factor and fibroblast growth factor. Journal of Neuroscience Research 2007; 85(-9-):1959-1969. >>> Brain-derived neurotrophic factor; fibroblast growth factor-1; Perilymph, artificial; albumin, guinea pig serum; Ear (scala tympani); Guinea-pig; 2002; 26 days; Controls received mp w/ vehicle; pumps replaced at day 13; peptides; tissue perfusion (scala tympani); animal info (male, female, pigmented, 250-300g, deafened).

P8080 Nagano,H., Wei,P.Z., Wen,C.Q., Jomori,T., Oku,H., Ikeda,T., Saito,Y., Tano,Y. Effects of kallidinogenase on ischemic changes induced by repeated intravitreal injections of endothelin-1 in rabbit retina. Current Eye Research 2007; 32(-2-):113-122. >>> Kallidinogenase; Saline; IV (marginal ear vein); Rabbit; 4 weeks; Controls received mp w/ vehicle; ischemia (retinal); animal info (male, New Zealand, 2.5-3.5 kg.).

P8738 Roehm,P., Hoffer,M., Balaban,C.D. Gentamicin uptake in the chinchilla inner ear. Hearing Research 2007; 230(-1-2-):43-52. >>> Gentamicin; Ear (round window); Chinchilla; 2002; 1, 3, 6, 14 days; 4, 8 hours; Comparison of transtympanic injections vs. mp; tissue perfusion (round window); animal info (male, female, chinchilla langier).

P8368 Wang,J., Ruel,J., Ladrech,S., Bonny,C., Van de Water,T.R., Puel,J.L. Inhibition of the c-Jun N-terminal kinase-mediated mitochondrial cell death pathway restores auditory function in sound-exposed animals. MOLECULAR PHARMACOLOGY 2007; 71(-3-):654-666. >>> Jun, c-, N-Terminal kinase Inhibitor-1, D-; peptide, D-TAT; Jun, c-, N-Terminal kinase Inhibitor-1-mutant; Perilymph, artificial; PBS; Ear (round window membrane); Guinea-Pig; 2001; 7 days; Controls received mp w/ vehicle, or inactive JNKI-1-mutant or TAT-empt peptide or contralateral untreated ear; dose-response (fig 6); comparison of acute infusion vs. hyaluronic acid gel vs.; enzyme inhibitor (c-Jun N-terminal kinase); peptides; animal info (pigmented, 250-300g.; sound trauma); D-JNKI-1 peptide contains a 10-amino acid HIV-TAT transporter sequece to facilitate its entry into cells; tissue perfusion (round window membrane).

P7898 Eshraghi,A.A., He,J., Mou,C.H., Polak,M., Zine,A., Bonny,C., Balkany,T.J., Van de Water,T.R. D-JNKI-1 treatment prevents the progression of hearing loss in a model of cochlear implantation trauma. OTOLOGY&NEUROTOLOGY 2006; 27(-4-):504-511. >>> Peptide, D-JNK inhibitor 1; Perilymph, artificial; Ear (cochlea); Guinea-pig; 2001; 1 week; Controls received mp w/ vehicle; no stress (see pg.507); enzyme inhibitor (c-Jun N-terminal kinases); peptides; mp primed overnight in 37 celsius ringer solution; "the specificity of this molecule is high and therefore should limit the occurence of any unwanted side effects." (pg.510).

P8176 Radeloff,A., Smolders,J.W.T. Brain-derived neurotrophic factor treatment does not improve functional recovery after hair cell regeneration in the pigeon. Acta Oto-laryngologica 2006; 126(-5-):452-459. >>> Brain-derived neurotrophic factor, recomb. human; PBS; albumin, chicken; Hank's solution; Ear (scala tympani); Bird (pigeon); 2002; 8 weeks; Controls received mp w/ vehicle or no treatment to contralateral ear; long-term study; pumps replaced every 14 days; ALZET brain infusion kit used; peptides; animal info (Columba livia, 6 months old, 320-580 grams); deafening of both ears; tissue perfusion (scala tympani).

R0239 Richardson,R.T., Noushi,F., O'Leary,S. Inner ear therapy for neural preservation. AUDIOLOGY AND NEURO-OTOLOGY 2006; 11(-6-):343-356. >>> Nerve growth factor; NT-3; adenovirus; brain-derived neurotrophic factor; perilymph, artificial; glial-derived neurotrophic factor; ciliary neurotrophic factor; fibroblast growth factor, acidic; fibroblast growth factor-1; fibroblast growth factor-2; fibroblast growth factor, basic; Ear (cochlea); ear (scala tympani); Guinea-pig; 1,2,4,8 weeks; 15-60, 11-12, 26 days; Comparison of polymers, hydrogels, gene therapy, cell-based therapy, and injections vs. mp; long-term study; pumps replaced; no stress (see pg. 350); half-life (p. 344), short in blood; gene therapy; peptides; animal info (deafened); Table 2; "The mini-osmotic pump device is ideally suited to studying the effects of neurotrophic factors in the cochlea experimentally." (p. 350).

P8388 Sendowski,I., Abaamrane,L., Raffin,F., Cros,A., Clarencon,D. Therapeutic efficacy of intra-cochlear administration of methylprednisolone after acoustic trauma caused by gunshot noise in guinea pigs. Hearing Research 2006; 221(-1-2-):119-127. >>> Methylprednisolone; perilymph, artificial; Perilymph, artificial; Ear (scala tympani); Guinea-Pig; 2001; 14 days; Controls received mp w/ vehicle, or non-implanted ear; dose-response (fig. 1); pumps replaced after 7 days of artifical perilymph; animal info (pigmented, 400-500g., acoustic trauma, gunshot); tissue perfusion (scala tympani).

P8059 Hara,H., Takeno,K., Shimogori,H., Yamashita,H. CGRP expression in the vestibular periphery after transient blockage of bilateral vestibular input. ORL-JOURNAL FOR OTO-RHINO-LARYNGOLOGY AND ITS RELATED SPECIALTIES 2005; 67(-5-):259-265. >>> Tetrodotoxin; Ear (cochlea perilymphatic space); Guinea-pig; 2002; 7 days; Controls received mp w/ sterile saline; post op. care (piperacillin sodium); animal info (male, Hartley, 600g.); tissue perfusion (cochlea).

P7765 Richardson,R.T., O'Leary,S., Wise,A., Hardman,J., Clark,G. A single dose of neurotrophin-3 to the cochlea surrounds spiral ganglion neurons and provides trophic support. Hearing Research 2005; 204(-1-2-):37-47. >>> NT-3, recomb. human; brain-derived neurotrophic factor; Ringer's solution; Ear (scalatympani); Guinea-pig; 2004; 28 days; Comparison of bolus infusion vs. mp; peptides; animal info (adult, pigmented Dunkin-Hartley, 455g.); tissue perfusion (scala tympani).

P7306 Shepherd,R.K., Coco,A., Epp,S.B., Crook,J.M. Chronic depolarization enhances the trophic effects of brain-derived neurotrophic factor in rescuing auditory neurons following a sensorineural hearing loss. Journal of Comparative Neurology 2005; 486(-2-):145-158. >>> Brain-derived neurotrophic factor, recomb. human; perilymph, artificial; Ringer's solution; albumin, recomb. guinea-pig; Ear (scala tympani); Guinea-Pig; 2004; 28 days; Controls received mp w/ artificial perilymph or untreated contralateral cochlea; functionality of mp verified by residual fluid, cannula connection and patency; no stress (see pg. 155); good methods; peptides; post op. care (carprofen, Baytril); mp primed 36-48 hours in 37 degrees celsius Ringer's solution; Electrode array also inserted into scala tympani; "We observed no evidence of mechanical trauma to cochlea following long-term implantation and AP or BDNF delivery." (p. 155); tissue perfusion (scala tympani).

P7529 Tanaka,K., Takemoto,T., Sugahara,K., Okuda,T., Mikuriya,T., Takeno,K., Hashimoto,M., Shimogori,H., Yamashita,H. Post-exposure administration of edaravone attenuates noise-induced hearing loss. European Journal of Pharmacology 2005; 522(-1-3-):116-121. >>> Edaravone; saline; Water; NaOH; Ear (cochlea); Guinea-pig; 2002; 12 hours; Controls received no treatment to left ear; pumps replaced, mp w/ saline used then replaced with mp with agent; stability verified for 24 hours; post op. care (antibiotic ointment); animal info (male, Hartley, 300-450 g); tissue perfusion (cochlea).

P7331 Wise,A.K., Richardson,R., Hardman,J., Clark,G., O'Leary,S. Resprouting and survival of guinea pig cochlear neurons in response to the administration of the neurotrophins brain-derived neurotrophic factor and neurotrophin-3. Journal of Comparative Neurology 2005; 487(-2-):147-165. >>> Brain-derived neurotrophic factor, recomb. human; NT-3; Ear (scala tympani); Guinea-Pig; 2004; 28 days; Controls received mp w/ Ringer's solution; cannula patency ascertained by visual inspection; tissue perfusion (scala tympani).

P6930 Gillespie,L.N., Clark,G.M., Marzella,P.L. Delayed neurotrophin treatment supports auditory neuron survival in deaf guinea pigs. NeuroReport 2004; 15(-7-):1121-1125. >>> Brain-derived neurotrophic factor; nerve growth factor; NT-3; NT-4/5; Ear (scala tympani, cochlea); Guinea-pig; 2004; 28 days; Tissue perfusion.

P7069 Jing,W., Ladrech,S., Pujol,R., Brabet,P., Van de Water,T.R., Puel,J.L. Caspase inhibitors, but not c-Jun NH2-terminal kinase inhibitor treatment, prevent cisplatin-induced hearing loss. Cancer Research 2004; 64(-24-):9217-9224. >>> z-DEVD-fmk; z-IETD-fmk; z-LEHD-fmk; z-FA-fmk; JNKI-1, D-; Perilymph, artificial; Ear (cochlea); Guinea-pig; 2001; 7 days; Controls received mp w/ vehicle; enzyme inhibitor (caspases (-3,-8,-9), cathepsinB, JNK); peptides; tissue perfusion (cochlea).

P7101 Le Prell,C.G., Yagi,M., Kawamoto,K., Beyer,L.A., Atkin,G., Raphael,Y., Dolan,D.F., Bledsoe,SC Jr, Moody,D.B. Chronic excitotoxicity in the guinea pig cochlea induces temporary functional deficits without disrupting otoacoustic emissions. Journal of the Acoustical Society of America 2004; 116(-2-):1044-1056. >>> AMPA; Perilymph, artificial; Ear (scala tympani); Guinea-pig; 2002; 2004; 14-56 days; Controls received mp w/ vehicle; dose-response (fig. 2); long-term study; pumps replaced at 14 or 28 day intervals; stress/adverse reaction: (see pg. 1045) middle ear infections; tissue perfusion (scala tympani).

P6918 Li,M., Ding,D.L., Zheng,X.Y., Salvi,R. Vestibular destruction by slow infusion of gentamicin into semicircular canals. Acta Oto-laryngologica 2004; 124(--):35-41. >>> Gentamicin; Hank's solution; Ear (semicircular canals); Chinchilla; 1007D; 7 days; Controls received mp w/ vehicle; Meniere's disease; microcatheter used; 27 gauge tubing used for cannulation; tissue perfusion (semicircular canals).

Q0251 Mills,D.M., Schmiedt,R.A. Metabolic Presbycusis: Differential Changes in Auditory Brainstem and Otoacoustic Emission Responses with Chronic Furosemide Applicationin the Gerbil. JARO 2004; 5(--):1-10. >>> Furosemide; Ear (round window niche); Gerbil; 2004; 3-7 days; Controls recieved a bulla vent tube (no mp); no stress (see pg. 2); animal info (young adult, Mongolian, 45-65g); dose-response.

P7104 Minami,S.B., Yamashita,D., Schacht,J., Miller,J.M. Calcineurin activation contributes to noise-induced hearing loss. Journal of Neuroscience Research 2004; 78(-3-):383-392. >>> FK-506; cyclosporin A; Perilymph, artificial; Ear (cochlea); Guinea-pig; 2002; 14 days; Controls received mp w/ vehicle, or contralateral untreated cochlea; dose-response (fig. 3); stress/adverse reaction: (see pg. 385) 4 of 43 animals developed middle ear infections; 4 of 43 animals had post surgical hearing loss; calcineurin inhibitors; "Systematic application may therefore have unwanted side effects that may be avoided by intracochlear perfusion by osmotic pump. The use of an osmotic pumps also allows relatively precise control over the timing and concertration of drugs applied to the tissues of the inner ear." (pg. 389); tissue perfusion (cochlea).

P6392 Okuda,T., Sugahara,K., Shimogori,H., Yamashita,H. Inner ear changes with intracochlear gentamicin administration in guinea pigs. Laryngoscope 2004; 114(-4-):694-697. >>> Gentamicin; Saline; Ear (cochlea); Guinea-pig; 2002; 14 days; Controls received mp w/ vehicle; pumps replaced at day 7; pump contained saline only for the first seven days ; PE-10 used; tissue perfusion (cochlea).

P6458 Olivius,P., Alexandrov,L., Miller,J.M., Ulfendahl,M., Bagger-Sjoebaeck,D., Kozlova,E.N. A model for implanting neuronal tissue into the cochlea. BRAIN RESEARCH PROTOCOLS 2004; 12(-3-):152-156. >>> Brain-derived neurotrophic factor; ciliary neurotrophic factor Ax1, human; Ear (scala tympani); Guinea-pig; 2002; 21-22 days; Pump replaced on days 11-12; post op. care (cyclosporine, doxycycline); tissue perfusion (scala tympani).

P7105 Roberson,D.W., Alosi,J.A., Cotanche,D.A. Direct transdifferentiation gives rise to the earliest new hair cells in regenerating avian auditory epithelium. Journal of Neuroscience Research 2004; 78(-4-):461-471. >>> Uridine, bromodeoxy-; Ear (cochlea); Bird (chicken); 2002; 3-11 days; Controls received untreated contralateral ear; functionality of mp verified by (epithelial immunohistochemistry); stability verified by epithelial immunohistochemistry; tissue perfusion (cochlea).

P6793 Stocks,R.M.S., Gould,H.J., Bush,A.J., Dudney,BW Jr, Pousson,M., Thompson,J.W. Ototoxic protection of sodium thiosulfate: Daily vs constant infusion. OTOLARYNGOLOGY-HEAD AND NECK SURGERY 2004; 131(-1-):115-119. >>> Thiosulfate, sodium; Ear (middle ear space); Guinea-pig; 2002; 18 days; Controls received no treatment to right ear; comparison of daily middle ear space injections vs. mp; pumps replaced after 7 days; multiple pumps per animal (2); "Continuous infusion of STS is the preferred method of administration." (p. 118) "STS continuously infused into the middle ear system provides a greater protective function than daily injection." (p. 119); tissue perfusion (middle ear space).

P6536 Sugahara,K., Shimogori,H., Okuda,T., Takemoto,T., Hashimoto,M., Yamashita,H. Cochlear administration of adenosine triphosphate facilitates recovery from acoustic trauma (temporary threshold shift). ORL-JOURNAL FOR OTO-RHINO-LARYNGOLOGY AND ITS RELATED SPECIALTIES 2004; 66(-2-):80-84. >>> Adenosine triphosphate; PPADS; Ear (cochlea); Guinea-pig; 2002; ; Post op. care (antibiotic ointment applied); PE-10 used to target the inner ear and fixed with dental cement; for recover period, pumps and catheters were filled with saline, then pumps replaced with reagent filled pumps; infusion of agents was 12 hours post pump replacement to allow for saline in catheter to be infused; PPADS is pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid solution; tissue perfusion (cochlea).

P6462 Takemoto,T., Sugahara,K., Okuda,T., Shimogori,H., Yamashita,H. The clinical free radical scavenger, edaravone, protects cochlear hair cells from acoustic trauma. European Journal of Pharmacology 2004; 487(-1-3-):113-116. >>> Edaravone; saline; NaOH; water; HCL; Ear (cochlea); Guinea-pig; 2002; 17 days; Controls received no treatment to contralateral ear; animals received mp w/saline for 3 days; then pumps replaced for mp w/edaravone; no stress (see pg. 115); post op. care (antibiotic ointment); edaravone is a free radical scavenger; tissue perfusion (cochlea).

P7209 Wimmer,C., Mees,K., Stumpf,T., Welsch,U., Reichel,O., Suckfuell,M. Round window application of D-methionine, sodium thiosulfate, brain-derived neurotrophic factor, and fibroblast growth factor-2 in cisplatin-induced ototoxicity. OTOLOGY&NEUROTOLOGY 2004; 25(-1-):33-40. >>> Methionine, D-; filoblast growth factor 2; thiosulfate, sodium petahydrate; brain-derived neurotrophic factor; Water; PBS; Ear (round window membrane); Guinea-Pig; 2001; 6 days; Controls received mp w/ saline; mp primed > 12 hours in saline; tissue perfusion (round window membrane).

P5672 Chelikh,L., Teixeira,M., Martin,C., Sterkers,O., Ferrary,E., Couloigner,V. High variability of perilymphatic entry of neutral molecules through the round window. Acta Oto-laryngologica 2003; 123(-2-):199-202. >>> Mannitol; Inulin;; Radio-isotopes; 3H tracer; saline; ethanol; Ear (round window); Guinea-pig; 1007D; 7 days; Tissue perfusion (round window).

P5811 Du,X.P., Yoo,T.J., Mora,R. Distribution of beta-tubulin in guinea pig inner ear. ORL-JOURNAL FOR OTO-RHINO-LARYNGOLOGY AND ITS RELATED SPECIALTIES 2003; 65(-1-):7-16. >>> Tubulin, beta; PBS; Ear (scala tympani); Guinea-pig; 2002; 14 days; Controls received mp w/ vehicle; tissue perfusion (cochlea); peptides.

P6159 Ekborn,A., Laurell,G., Ehrsson,H., Miller,J. Intracochlear administration of thiourea protects against cisplatin-induced outer hair cell loss in the guinea pig. Hearing Research 2003; 181(-1-2-):109-115. >>> Thiourea; Perilymph, artificial; water, sterile; Ear (cochlea); Guinea-pig; 2002; 14 days; good methods p. 111; microtip catheter was held in place using cyanoacrylate glue at the bulla defect, which was then sealed with dental cement; cites a detailed cannulation method; tissue perfusion (cochlea).

P5669 Gillespie,L.N., Clark,G.M., Bartlett,P.F., Marzella,P.L. BDNF-induced survival of auditory neurons in vivo: Cessation of treatment leads to accelerated loss of survival effects. Journal of Neuroscience Research 2003; 71(-6-):785-790. >>> Brain-derived neurotrophic factor; Ear (cochlea); Guinea-pig; 2004; 4 weeks; Peptides; BDNF was recombinant human; tissue perfusion (cochlea).

P5659 Horiike,O., Shimogori,H., Ikeda,T., Yamashita,H. Protective effect of edaravone against streptomycin-induced vestibulot oxicity in the guinea pig. European Journal of Pharmacology 2003; 464(-1-):75-78. >>> Streptomycin; Saline; Ear (cochlea); Guinea-pig; 2002; 24 hours; tissue perfusion (round window).

P6077 Lang,H., Schulte,B.A., Schmiedt,R.A. Effects of chronic furosemide treatment and age on cell division in the adult gerbil inner ear. JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY 2003; 4(-2-):164-175. >>> Furosemide; Ear (cochlea); Gerbil; 2004; 1 week; No stress (p. 165); tissue perfusion (cochlea).

P5832 Miller,A.L., Prieskorn,D.M., Altschuler,R.A., Miller,J.M. Mechanism of electrical stimulation-induced neuroprotection: effects of verapamil on protection of primary auditory afferents. Brain Research 2003; 966(-2-):218-230. >>> Verapamil; Perilymph, artifical; Ear (cochlea); guinea-pig; 2002; 6 weeks; Pumps replaced every two weeks; 2 week stability verified by high pressure liquid chromatography p. 220; good methods p.220; 3 day recovery post implant; tissue perfusion (cochlea).

P6098 Takeda,T., Sawada,S., Takeda,S., Kitano,H., Suzuki,M., Kakigi,A., Takeuchi,S. The effects of V(2) antagonist (OPC-31260) on endolymphatic hydrops. Hearing Research 2003; 182(-1-2-):9-18. >>> OPC-31260; Saline; Ear (cochlea); Guinea-pig; 2002; ; Controls received mp w/ vehicle; OPC-31260 is a vasopressin type-2 antagonist; insertion site of the cannula was sealed with biobonde (biomedical adhesive); tissue perfusion (cochlea).

P6130 Wang,J., Van de Water,T.R., Bonny,C., de Ribaupierre,F., Puel,J.L., Zine,A. A peptide inhibitor of c-Jun N-terminal kinase protects against both aminoglycoside and acoustic trauma-induced auditory hair cell death and hearing loss. Journal of Neuroscience 2003; 23(-24-):8596-8607. >>> D-JNKI-1; Perilymph, artificial; Ear (scala tympani); Guinea-pig; 2001; 7 days; Controls received mp w/ vehicle; enzyme inhibitor (JNK); D-JNKI-1 is a C-JUN N-terminal kinase (JNK); glass pipette was glued to PE-50 and pressed against cochlea; tissue perfusion (scala tympani).

P6703 Wang,J., Faulconbridge,R.V.L., Fetoni,A., Guitton,M.J., Pujol,R., Puel,J.L. Local application of sodium thiosulfate prevents cisplatin-induced hearing loss in the guinea pig. Neuropharmacology 2003; 45(-3-):380-393. >>> Thiosulfate, sodium; Perilymph, artificial; water, sterile distilled; Ear (cochlea); Guinea-pig; 2001; 7 days; Controls received mp w/ vehicle; stress/adverse reaction: (see pg.381) "Seven animals died during the course of the CDDP treatment (probably from the toxic effects of CDDP)" (p.381); cancer; "Perfusion of STS into the cochlea via an osmotic minipump completely prevented CDDP-induced hearing loss" (p.391); pump/catheter schematic (p.381); tissue perfusion (cochlea).

P5872 Wang,X.B., Truong,T., Billings,P.B., Harris,J.P., Keithley,E.M. Blockage of immune-mediated inner ear damage by etanercept. OTOLOGY&NEUROTOLOGY 2003; 24(-1-):52-57. >>> Etanercept; PBS; keyhole limpet hemocyanin; Ear (scala tympani); Guinea-pig; 2001; 7 days; Controls received mp w/ PBS or KLH; Etanercept is a TNF receptor; keyhole limpet hemocyanin is (KLH); tissue perfusion (scala tympani).

P5673 Wolters,F.L.C., Klis,S.F.L., de Groot,J.C.M.J., Hamers,F.P.T., Prieskorn,D.A., Miller,J.M., Smoorenburg,G.F. Systemic co-treatment with alpha-melanocyte stimulating hormone delays hearing loss caused by local cisplatin administration in guinea pigs. Hearing Research 2003; 179(-1-2-):53-61. >>> Cisplatin; Saline; Ear (cochlea); Guinea-pig; 2002; 1 week; Tissue perfusion (cochlea).

P5983 Zou,J., Bretlau,P., Pyykkoe,I., Toppila,E., Olovius,N.P., Stephanson,N., Beck,O., Miller,J.M. Comparison of the protective efficacy of Neurotrophins and antioxidants for vibration-induced trauma. ORL-JOURNAL FOR OTO-RHINO-LARYNGOLOGY AND ITS RELATED SPECIALTIES 2003; 65(-3-):155-161. >>> Brain-derived neurotrophic factor; ciliary neurotrophic factor; Ear (scala tympani); Guinea-pig; 2002; 14 days; tissue perfusion (cochlea); comparison of RWM injections vs. mp; peptides.

R0213 Duan,M.L., Ulfendahl,M., Laurell,G., Counter,A.S, Pyykko,I., Borg,E., Rosenhall,U. Protection and treatment of sensorineural hearing disorders caused by exogenous factors: experimental findings and potential clinical application. Hearing Research 2002; 169(--):169-178. >>> Liposomes, cationic; Ear (cochlea); Guinea-pig; ; Gene therapy; tissue perfusion (cochlea).

P5579 Foster,P.K., Luebke,A.E. A model for perilymphatic fistula induced hearing loss in the guinea pig cochlea. Hearing Research 2002; 167(-1-2-):175-179. >>> Perilymph, artificial; Ear (scala tympani); guinea-pig; ; some animals also received an air bubble ~1.5-2 microliters infused into the scala tympani; tissue perfusion (scala tympani).

P5481 Himeno,C., Komeda,M., Izumikawa,M., Takemura,K., Yagi,M., Yang,W.P., Doi,T., Kuriyama,H., Miller,J.M., Yamashita,T. Intra-cochlear administration of dexamethasone attenuates aminoglycoside ototoxicity in the guinea pig. Hearing Research 2002; 167(-1-2-):61-70. >>> Dexamethasone; Perilymph, artificial; Ear (cochlea); guinea-pig; 2002; 14, 28 days; Controls received mp w/ vehicle; pumps replaced after 14 days; no stress (see pg. 67); "The current study indicates that intra-cochlear administration using osmotic pumps can provide a stable and continuous delivery of Dexamethasone without causing functional changes or tissue damage." (p. 67); tissue perfusion (cochlea).

P5540 Lalwani,A.K., Han,J.J., Castelein,C.M., Carvalho,G.J., Mhatre,A.N. In vitro and in vivo assessment of the ability of adeno-associated virus-brain-derived neurotrophic factor to enhance spiral ganglion cell survival following ototoxic insult. Laryngoscope 2002; 112(-8-):1325-1334. >>> Virus, adeno-associated; Gene, green fluorescent protein; Gene, brain-derived neurotrophic factor; PBS; Ear (cochlea); Guinea-pig; 1007D; 1 week; Gene therapy; cochlea cannulated with PE10 attached to PE50; virus contained gene for brain-derived neurotrophic factor and/or green fluorescent protein; tissue perfusion (cochlea).

R0164 Lalwani,A.K., Jero,J., Mhatre,A.N. Current issues in cochlear gene transfer. Audiol.Neurootol. 2002/5; 7(-3-):146-151. >>> Gene vectors; Ear (cochlea); Guinea-pig; 1007D; ; Gene therapy; review of various cochlear gene delivery methods; diagram of the various delivery methods (p. 147); tissue perfusion (cochlea).

R0183 Lalwani,A.K., Jero,J., Mhatre,A.N. Developments in cochlear gene therapy. GENETIC HEARING IMPAIRMENT: ITS CLINICAL PRESENTATIONS 2002; 61(-;-):28-33. >>> ; Ear; ; Gene therapy; review of gene vectors and routes of delivery for cochlear gene therapy; tissue perfusion (cochlea).

P5452 Matsuoka,H., Kwon,S.S., Yazawa,Y., Barbieri,M., Yoo,T.J. Induction of endolymphatic hydrops by directly infused monoclonal antibody against type II collagen CB11 peptide. Annals of Otology Rhinology and Laryngology 2002; 111(-7-):587-592. >>> Antibody, anti-CB11 monoclonal; Ear (scala tympani); Guinea-pig; 2002; 14 days; Controls received mp w/ mouse serum; tissue perfusion (scala tympani).

P5336 Schmiedt,R.A., Lang,H.N., Okamura,H., Schulte,B.A. Effects of furosemide applied chronically to the round window: A model of metabolic presbyacusis. Journal of Neuroscience 2002; 22(-21-):9643-9650. >>> Ouabain; Saline; Ear (round window); Gerbil; 2004; 28 days; Tissue perfusion (round window).

P5315 Shepherd,R.K., Xu,J. A multichannel scala tympani electrode array incorporating a drug delivery system for chronic intracochlear infusion. Hearing Research 2002; 172(-1-2-):92-98. >>> Neomycin; Kanamycin; Furosenide; PBS; ear (scala tympani); Guinea-pig; 2004; 28 days; Tissue perfusion (round window); functionality of mp verified by residual volume; diagram of pump and electrode assembly (p. 94); catheter patency assessed by passing fluid through the line at the end of the experiment; Neomycin infused in pilot study; Kanamycin and furosenide were co-infused in a second study.

P5009 Shinohara,T., Bredberg,G., Ulfendahl,M., Pyykko,I., Olivius,N.P, Kaksonen,R., Lindstrom,B., Altschuler,R., Miller,J.M. Neurotrophic factor intervention restores auditory function in deafened animals. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2002; 99(-3-):1657-1660. >>> Brain-derived neurotrophic factor; Ciliary neurotrophic factor; Neomycin;; Perilymph, artificial; Ear (scala tympani); guinea-pig; 2002; 26 days; controls received mp w/ vehicle; tissue perfusion (cochlea, scala tympani); pumps replaced at day 15; peptides; catheter filled with perilymph and 10% neomycin; pump filled with vehicle or neurotrophic factor solution; 48-hr infusion of neomycin to cause deafness followed by 12 or 26 day infusion of neurotrophic factor pump reservoir..

P5370 Spiess,A.C., Lang,H.N., Schulte,B.A., Spicer,S.S., Schmiedt,R.A. Effects of gap junction uncoupling in the gerbil cochlea. Laryngoscope 2002; 112(-9-):1635-1641. >>> Proadifen; Ear (round window niche); Gerbil; 2001; 2002; 6-7 or 11-14 days; Tissue perfusion (bulla); no stress (see pg. 1637); Proadifen, also called SKF-525A, is a gap junction uncoupler; the pump and cannula were gas-sterilized prior to filling (note: manufacturer does not recommend sterilizatioin of pumps); "The animals experienced no long-term trauma from either the surgery or the extra bulk of the pump." (p. 1637).

P5043 Wang,J., Dib,M., Lenoir,M., Vago,P., Eybalin,M., Hameg,A., Pujol,R., Puel,J.L. Riluzole rescues cochlear sensory cells from acoustic trauma in the guinea-pig. Neuroscience 2002; 111(-3-):635-648. >>> Riluzole; Perilymph, artificial; Ear (cochlea); guinea-pig; 2001; 7 days; controls received mp w/ vehicle; tissue perfusion (cochlea); 2-day recovery period. Schematic of pump infusing to inner ear (p. 636). Riluzole is a neoroprotective agent (also called 1-amino-6-trifluoromethoxy benzothiazole). Paper states the use of 1003D, but specifications indicate model 2001 was used.

P4856 Hoffer,M.E., Allen,K., Kopke,R.D., Weisskopf,P., Gottshall,K., Wester,D. Transtympanic versus sustained-release administration of gentamicin: Kinetics, morphology, and function. Laryngoscope 2001; 111(--):1343-1357. >>> Gentamicin sulfate; Water, sterile; Ear; Chinchilla; 2001; 7 days; Dose-response (graph, table p. 1349); comparison of transtympanic injections vs. mp/; IntraEar catheter used; Meniere's Disease; Vertigo; tinnitus; tissue perfusion.

P4739 Kopke,R.D, Jackson,R.L, Li,G, Rasmussen,M.D, Hoffer,M.E, Frenz,D.A, Costello,M, Schultheiss,P, Van De Water,T.R  PNAS 2001; 98(-10-):5886-5891. >>> Transforming growth factor; insulin-like growth factor I; retinoic acid; brain-derived neurotrophic factor;; PBS; BSA;; Ear (vestibule); Guinea-pig; 2002; 4 weeks; Controls received mp w/ vehicle; pumps replaced after 2 weeks; peptides; IntraEAR catheter used; GFI group pumps filled with TGF, IGF and Retinoic acid; GFII group pumps filled with TGF, IGF, BDNF and retinoic acid; tissue perfusion (vestibule).

P4821 Luebke,A.E., Steiger,J.D., Hodges,B.L., Amalfitano,A. A modified adenovirus can transfect cochlear hair cells in vivo without compromising cochlear function.. Gene Therapy 2001; 8(--):789-794. >>> Cisplatin; Saline; Ear (cochlea); guinea-pig; 2002; ; tissue perfusion (scala tympani); dose-response (Fig. 1-8); ototoxicity; in-house cochlear cannula used (modified); hearing loss; "the pump model has several advantages: 1) there appears to be less inter-animal variability than via systemic administration; 2) cisplatin dosage can be studied parametrically; 3) the effects of systemic toxicity are avoided" (p. 144).

P4742 Tang,W, Seidman,M.D, Henig,J.P, Shulman,A, Stracher,A  International Tinnitus Journal 2001; 7(-1-):4-12. >>> Leupeptin;; Hank's solution;; ear (round window);; guinea-pig;; 2002;; 8 weeks;; Controls received mp w/ vehicle; tissue perfusion (bulla); long-term study, pumps replaced every 13 days; IntraEAR catheter used; Leupeptin is a potent calpain inhibitor; neuroprotection; buprenorphine given as postoperative analgesic; chloramphenicol given as prophlactic antibiotic;.

R0146 Wanamaker,H.H. Perfusion of the inner ear; basic science considerations. Curent Opinion in Otolarynology&Head and Neck Surgery 2001; 9(--):329-332. >>> ; ear; ; IntraEar catheter used; review article describing ear delivery, dose response; ALZET and IntraEAR catheter mentioned p. 330; tissue perfusion.

P4733 Conlon,B.J, Smith,D.W  Acta Otolaryngol. 2000; 120(--):596-599. >>> Neomycin; lipoic acid, alpha; Saline; Ear (round window); Guinea-pig; 2ML4; 7 days; Controls received mp w/ vehicle; tissue perfusion (round window); no stress (see pg. 597); Neomycin antibiotic solution was 5%; micro polyurethane tubing used; the authors state that ALZET delivery system more closely approximates the clinical situation of repeated otic application, with minimal middle ear trauma..

P4730 Duan,M., Agerman,K, Ernfors,P., Canlon,B. Complementary roles of neurotrophin 3 and a N-methyl-D-aspartate antagonist in the protection of noise and aminoglycoside-induced ototoxicity.. PNAS 2000; 97(-13-):7597-7602. >>> NT-3; Amikacin;; Perilymph, artificial;; Ear (cochlea);; guinea-pig;; 2ML2;; 15 days;; Antibiotic; Controls received mp w/ vehicle; tissue perfusion (scala tympani); Amikacin is an aminoglycoside antibiotic; Group 1 received amikacin, Group 2 received vehicle, Group 3 received amikacin and NT-3; All treatment groups received drug for 1 day, followed by 2 weeks perilymph;.

P6333 Li,G, Frenz,D.A, Brahmblatt,S., Feghali,J.G., Ruben,R.J., Berggren,D., Arezzo,J., Van De Water,T.R  Neurotoxicology 2000; 22(--):163-176. >>> Methionine, L-; PBS, sterile; Ear (round window membrane); Rat; 2002; 12 days; Controls received no treatment; comparison of IP injections vs. mp; cancer (breast); cyanoacrylate adhesive; tissue perfusion (round window membrane).

P4743 Shimogori,H, Yamashita,H  Neuroscience 2000; 294(--):21-24. >>> Betamethasone;; Saline;; ear (cochlea);; guinea-pig;; 2002;; 2 weeks;; Controls received mp w/ vehicle; tissue perfusion (scala tympani); glucocorticoids; local and systemic antibiotics given to prevent infection;.

P5005 Shoji,F., Miller,A.L., Mitchell,A., Yamasoba,T., Altschuler,R.A., Miller,J.M. Differential protective effects of neurotrophins in the attenuation of noise-induced hair cell loss. Hearing Research 2000; 146(--):134-142. >>> NT-3; Brain-derived neurotrophic factor; Perilymph, artificial; Ear (scala tympani); guinea-pig; 2002; 12 days; controls received mp w/ vehicle; tissue perfusion (cochlea); functinality of mp verified by residual volume assessment; peptides; in-house catheter created for tissue perfusion;.

P4830 Yang,G.S.Y., Song,H.T., Keithley,E.M., Harris,J.P. Intratympanic immunosuppressives for prevention of immune-mediated sensorineural hearing loss.. American Journal of Otology 2000; 21(--):499-504. >>> Dexamethasone;; PBS;; Ear (round window membrane);; guinea-pig;; 2002;; ; Controls received mp w/ vehicle; tissue perfusion (bulla); comparison of IP injections vs. mp; multiple pumps per animal (2) (one containing dexamethasone for one ear, the other containing PBS for the other ear);.