Index 341. Cadherin, 23, Calcium, binding proteins, dysregulation, ARHL, hair cell damage, 285

Transcription

1 Index A1555G mutation, 226 Acidity, endolymph, 71 Acoustic overstimulation axon growth, effect on central auditory system, effects in cat, 265 effects in chinchilla, 264 fiber degeneration in cochlear nucleus, pathology, 195ff reorganization of cochlear nucleus, 265 terminal degeneration, 265 See also Acoustic Trauma; Noise Exposure; Noise-induced hearing loss (NIHL) Acoustic trauma, see Acoustic Overstimulation; Noise Exposure; Noise-induced hearing loss (NIHL) Acquired hearing loss, 1ff cortex and tinnitus, See also Autoimmune inner ear disease (AIED); Drug-induced hearing loss; Noise-induced hearing loss (NIHL) Adenosine, effects on hearing loss, Adhesion proteins, Age-related hearing loss, 4ff, 145ff See also ARHL; Presbycusis Aging, cellular, changes in function of central auditory system, hair cell density, 151 progression of ARHL in humans, 146ff Ahl genes, hearing loss, 158 Alport syndrome, Alprazolam, tinnitus, Ames waltzer mouse, 27 Aminoglycoside antibiotics, 2, 219ff See also Aminoglycosides Aminoglycoside-induced signaling pathways, 242 Aminoglycosides, A1555G mutation, 226 adverse side effects, animal models, antioxidant therapy, 245 apoptosis, 241 biochemical actions, calcium interactions, 235 caspase activation, 241 caspase-independent pathways, 243 cell death, cochlear pathology, 231 effects on cochlear hair cells, 231 effects on vestibular hair cells, 231, 232 history as ototoxic drug, incidence of ototoxicity, interactions with calcium, 235 interactions with diuretics, 219 JNK apoptotic pathways, mechanism of therapeutic action, 222 mitochondrial mutations, oxidative stress, pathophysiology, 229 pharmacokinetics, protection of inner ear, risk factors, transport mechanisms into cells, uptake by hair cells, vestibular pathology, 232 Angiosclerotic degeneration, 146 Animal models, aminoglycoside ototoxicity, ARHL, 157ff autoimmune inner ear disease (AIED), 138ff cisplatin ototoxicity, human genetic hearing loss, ototoxicity, tinnitus, 116ff Anoikis, and apoptosis, 211 Antibiotics, see Aminoglycoside Antibiotics Antineoplastic agents, see Cisplatin 339

2 340 Index Antioxidants, protection against free radical damage, 284, protection of spiral ganglion neurons, 303 Antioxidant systems, cochlear stress, 213 Antioxidant therapy, aminoglycosides, 245 ARHL, 172 cisplatin, 244 noise trauma, 213 Apoptosis, aminoglycosides, 241 Bcl-2 family proteins, caspases, 277 cisplatin, 239 cochlear, 275ff free radicals, 281 general principles, hair cells, 208ff inhibition by small molecules, 303 JNK jun signaling, mitochondrial pathway, noise-induced hearing loss, 205, 208ff p53 transcription factor, apoptosis, 283 transcription factor, 283 regulation as protection against drugs, 287 regulation as protection against noise, 285 transcriptional regulation, 278ff Arachidonic acid metabolism, ARHL, 145ff animal models, 157ff AVCN cells, B6 mice inferior colliculus, BALB mice, Brn4, 163 calcium dysregulation, CBA mice, 164 CBA mice inferior colliculus, Cdh23 ahl, , 161 cell repair and replacement, 175 cellular aging mechanisms, 171ff central auditory system in animals, 163ff central auditory system in humans, central pathology, 156 changes in efferent feedback, changes in speech processing, 157 classification, 149ff cochlear conductive, 154 cochlear nucleus in animals, cochlear pathology in human, 149ff cochlear pathology in mice, 159 DFN3, 163 effect of caloric restriction, 180 effect of diabetes mellitus, 177ff effect of environmental factors, 175ff effect of mineralocorticoid level, 177, 178 effect of noise, 176 effect of ototoxins, 176 effect of stress, Fischer-344 rats, free radical theory, 173 functional changes in central auditory system, gender differences in humans, genes in mice, hair cells, historical accounts of research, 146ff human, 145ff inferior colliculus of animals, knockout mice, lifestyle effects, 176 mitochondrial clock theory, 173 mitochondrial variables, 173 mixed, mouse models, 145, 158ff neural, neural changes in animals, oxidative stress and cell injury, perceptual changes due to peripheral pathology, 168 peripheral aspects in humans, 149ff pharmacological treatment, possible causes and protection, 287 prevention and treatment, progression with aging in humans, 146ff protection against, 287 restoration of hearing loss, right ear advantage, risk factors, 175ff Schuknecht, 149, 155 sensory, 152 sensory changes in animals, speech reception with central pathology, 169 stria vascularis, stria vascularis in animals, See also Presbycusis Aspirin, prevention of gentamicin-induced hearing loss, 245, 286 Asymptotic threshold shift (ATS), Atoh1, hair cell regeneration, ATP and adenosine, protection against hearing loss, ATPases, cochlear, 57ff, 79 ATP2B1 (PMCA1b), ATP2B2 (PMCA2), ATP6V1B1, 57, 58, 79 ATP6VIE, 58 ATPV0A4, 79 Audiology, autoimmune inner ear disease (AIED), 135

3 Index 341 Auditory cortex, electric and magnetic stimulation, 114 pathology, reorganization and tinnitus, 114 tinnitus, 108ff Auditory pathology, 1ff AUNA, 21 Autoimmune inner ear disease (AIED), 131ff chronic therapies, 137 classification, 136 clinical presentation, 134 diagnosis, 134ff epidemiology, 131ff experimental therapies, 138 history, lab tests, 135ff mechanisms, 140ff treatment, type II collagen, 138 AVCN (anterior ventral cochlear nucleus), age-related changes, synaptic changes with ARHL, 165 Axon growth, following acoustic overstimulation, B6 mice, endocochlear potentials, inferior colliculus and ARHL, Balance, see Vestibular dysfunction BALB mice, ARHL, endocochlear potential, 159 Bartter syndrome, 78 Basilar papilla, hair cell regeneration, Bauer Brososki model, tinnitus, 118ff Bcl-2 family proteins, apoptosis, cell death, 240 posttranslational regulation, 279 BDNF, spiral ganglion neuron support, BHLH gene, hair cell regeneration, 326 Birds, hair cell regeneration, Blood flow regulation, cochlea, 63ff Bovine serum albumin, autoimmune inner ear disease (AIED), 139 Branchiootorenal syndrome, 16 Brn4, ARHL, 163 BRN4, mouse, 81 BSND (barttin), 78 Cadherin, 23, See also CDH23 Calcium, binding proteins, dysregulation, ARHL, hair cell damage, 285 homeostasis, endolymph, interactions with aminoglycosides, 235 ion regulation, intracellular, 58ff regulation, Cdh23 gene, 174 signaling and support of spiral ganglion neuron survival, Caloric restriction, effect on ARHL, 180 Calretinin, 59 Carbon dioxide, CBF, Caspase-independent pathways, aminoglycosides, 243 Caspases, activation by aminoglycosides, 241, 242 apoptosis, 277 hair cell death after cisplatin, noise, , 212 CBA mice, see Animal models, aminoglycoside ototoxicity; Mouse model, aminoglycoside ototoxicity CDH23, 18, 26, 27 calcium regulation, 174 Cdh23 ahl, age-related pathology, , 161, 174 Cell death, 2 ff, 275ff aminoglycosides, calcium, 285 cisplatin, general principles, hearing loss, 275ff impulse noise, 211 pathways from ototoxic drugs, 238ff See also Apoptosis; Necrosis Cell injury oxidative stress, See also Drug-induced hearing loss; Noise-induced hearing loss (NIHL) Cell repair and replacement, ARHL, 175 Cell survival, transcriptional regulation, 278ff Cellular aging mechanisms in ARHL, 171ff theories, Cell volume regulation, Central auditory pathology, changes in perception, temporal processing, 169 Central auditory system, ARHL in animals, 163ff ARHL in humans, effects of acoustic overstimulation, effects of cochlear trauma, 257ff functional changes with age, plasticity, 258ff structural changes with age, 156 CGRP, 66 CHARGE syndrome, 31

4 342 Index Cisplatin, adverse side effects, 219ff, 223 age related to risk factors, 225 animal models for ototoxicity, Bcl-2 family proteins, 240 binding to molecules, 234 biochemical actions, 234 caspase inhibition, cell death, cochlear pathology, effect on outer hair cells, , effect on stria vascularis, 230 free radicals, genetic disposition to risk factors, hearing loss, history as ototoxic drug, incidence of ototoxicity, 224 mechanism of therapeutic action, 222 ototoxic stress, pathophysiology, 229 pharmacokinetics, protection of inner ear, risk factors, tinnitus, 109 vestibular pathology, CLCNKA, Bartter syndrome, 78 CLCNKB, Bartter syndrome, 78 COCH (cochlin), 14, 80 Cochlea age related changes in mice, excitotoxicity, free radical generation, protection, 275ff role of BDNF, role of NT-3, stem cells, strategies for restoring after trauma, 321ff vascular pathology, See also Inner ear; individual cochlear structures Cochlear ablation, effect on cochlear nucleus, effects on central auditory system, 259ff Cochlear blood flow (CBF), and noise, 206ff pathology, protection against trauma, regulation, 63ff Cochlear conductive ARHL, 154 Cochlear damage effects on cochlear nucleus, 258ff tinnitus, 105ff See also Cochlear pathology, aminoglycosides Cochlear homeostasis, 49ff Cochlear nucleus, ARHL in animals, cellular changes with ARHL, degeneration after cochlea damage, 258ff growth factors and synaptic reorganization, 267 noise-induced changes, 265 physiological changes with ARHL, plasticity after cochlea damage, 259ff reorganization after acoustic overstimulation, 265 synaptic reorganization following noise exposure, terminal degeneration, 258ff tinnitus, 108ff Cochlear pathology, aminoglycosides, 231 ARHL, 149ff ARHL in mice, cisplatin, dynamics after noise exposure, 204ff noise-induced, Cochlear structures, in ARHL types, 149ff Cochlear trauma, effects on central auditory system, 257ff Cochlear treatment, challenges, 332 Cogan s syndrome, autoimmune inner ear disease (AIED), 141 Collagen, in genetic hearing loss, Collagen genes (COL), 14, 20 Conditioned avoidance method, tinnitus, 125 Conditioning principles, tinnitus, 116 Connexin-related disorders, 22, 74ff Connexins 26GJB2 mutations, deafness, 22 23, 74ff transfection in HeLa cells, 35 types in cochlea, 22, 23, See also Gap junction proteins CREB, regulation, Critical level, noise exposure, 205 CX, see Connexins Cyclooxygenase pathway, 50 Cyclosporin, and protection of hair cells, Cytokines, autoimmune inner ear disease (AIED), 133ff Cytomegalovirus (CMV), autoimmune inner ear disease (AIED), 140 Cytotoxic T cell damage, autoimmune inner ear disease (AIED), 141 Deafness, historic, 1 incidence, 1 Deafness-related genes, 13 See also DFN genes

5 Index 343 Deaf-waddler mouse, Degeneration, cellular, in ARHL, 149ff, 158 central, 259, 263, 268 inner hair cells, 31 organ of Corti, 24, 139, 152 outer hair cells, 230 spiral ganglion, 138, 142, 152, 230, 263ff, 293, 299ff spiral limbus, 155 stereocilia, 27 stria vascularis, 76, 140, 141, 153, 154, 158, 161ff transsynaptic, central, 258 Developing countries, ototoxicity, 225 Developmental programs, reactivation in organ of Corti, 324ff DFN genes DFN3, 13 DFN3, ARHL, 163 DFNA, 21 DFNA1, 13 DFNA2, 28, 31 DFNA11, 18, 25, 31 DFNA15, 33 DFNA22, 24 DFNA36, 31 DFNB, 21 DFNB1, 13, 22, 23 DFNB2, 18 DFNB3, 25 DFNB4, 20 DFNB12, 26 DFNB17, 29 DFNB23, 18 DFNB28, 30 DFNB33, 29 DFNB36, 36 DFNB37, 24 DFNM, 21 DFNX, 21 DFNY, 21 Diabetes mellitus, effect on ARHL, 177ff Diaphanous, 13 Diuretics, 219 Drug-induced hearing loss, 4ff, 219ff See also Aminoglycosides; Cisplatin Drugs, ototoxic, 219ff Ear, see Inner Ear EDN3, 16 EDNRB, 16 Efferent feedback, ARHL changes, Eighth nerve, ARHL, Electrical stimulation, protection of spiral ganglion neurons, Embryonic stem cells, 333 Emotional stress, Ménière s disease, 81 Endocochlear potential, aminoglycosides, 229 ARHL, , 159 ARHL in animals, BALB mice, cisplatin, 229 melanocytes, 15 mice, pathologies, 75, 305 pendrin, 20 source, 61, 68ff, 73 Endolymph, vestibular, 78, 81 Endolymph and ATP, 289 composition, 67 gene transfer, 326, 328 in Jervell-Lange-Nielsen Syndrome, 76 leakage after noise trauma, leakage in Ménière s disease, in Pendred Syndrome, 76 potassium circulation, 22, 68 regulation, 66ff Endolymphatic hydrops, Ménière s disease, 79ff tinnitus, 103 Endolymphatic sac, and cochlear endolymph, 81 autoimmune inner ear disease (AIED), Energy metabolism, 50ff ENU mutagenesis, Environmental factors, effect on ARHL, 175ff Epinephrine, potassium homeostasis, 70 Excitotoxicity, as neuronal trauma, cochlea, hair cells, 199 intracellular mediators of, 299 protection from by LOC efferents, 299 spiral ganglion cells, EYA1, 16 Fiber degeneration following acoustic overstimulation, See also Degeneration, cellular, in ARHL, spiral ganglion Fibroblast growth factors, see Growth factors, synaptic reorganization following noise exposure Fibrocytes, pathology, 199 Fischer-344 rats, ARHL, FK506, and protection of hair cells,

6 344 Index FOX1, mouse model, 81 Free radicals, 5 aminoglycosides, apoptosis, 281 cisplatin, cochlea, ototoxic drugs, 235ff protection by antioxidants, 52 53, 284, protection of hair cells, redox homeostasis, 50, 236 source of hair cell death, 283 stress, 53 stress response, 281 See also Oxidative Stress Free radical theory, ARHL, 173 GABA, and tinnitus, ARHL in inferior colliculus, 167 synaptic reorganization following noise exposure, Gap coding, changes in CBA mice with age, Gap junction proteins, 22ff endocochlear potential, 75 GJA1 (Cx43), GJA7 (Cx45), 76 GJB2 (Cx26), GJB2, 35delG, 167delT, 22 GJB6 (Cx30), 23 See also Connexins Gap junctions, 74ff GDNF, receptors, 293 protectant, 285 spiral ganglion survival, 292 Gender, differences in hearing loss in humans, Gene identification, methodology, 28ff Genes, ARHL in mice, hair cell proliferation, Genetic factors, aminoglycoside ototoxicity, cisplatin ototoxicity, Genetic hearing loss, 9ff, 288 definitions, 11ff websites, 14 Genetic susceptibility, aminoglycosides, 238 Gentamicin, see Aminoglycosides GJA, GJB, see Gap junction proteins Glucose, metabolism, 51 transporters, 50 Glutamate, hair cell pathology, 200 tinnitus, 107 Glutamate buffering, 61ff Glutathione, 53, 236 cisplatin, 234, 237, 244 noise, 284, 304 Glutathione-linked enzymes, 52 ARHL, 173 noise, 213 Growth factors, synaptic reorganization following noise exposure, 267 Hair cell density, changes with age, 151 Hair cell proliferation, genes, Hair cell regeneration, 4, 321ff Atoh1, basilar papilla, bhlh gene, 326 birds, challenges to treatment, 332 differentiation of hair cells from stem cells, 331 mammals, 324 molecular control, nonmammalian vertebrates, 322 reactivation of developmental programs, 324ff use of cochlear nonsensory cells, use of supporting cells, vestibular system, 324 Hair cells aminoglycoside uptake, ARHL, death pathways, 208ff differentiation from stem cells, 331 effect of cisplatin, , free radicals and cell death, 50, 172, 206, 235ff, 283 protection from cell death, 243ff, 283ff repair and regeneration, 324ffls support of spiral ganglion neurons, therapeutic intervention, 283ff See also Inner hair cells; Outer hair cells Hair cell transduction, pathology, 198ff Harmonin b, Hearing loss aging humans, 146ff ahl genes, 158 aminoglycosides, categories, 10 causes, 3ff, 322 cell death, 275ff challenges to treatment, 332 cisplatin, drug-induced, 219ff genetic, 288

7 Index 345 ototoxicity, 219ff pathophysiology from ototoxic drugs, 229 preconditioning of protective mechanisms, restoration in ARHL, See also Age-related Hearing Loss; Drug-induced hearing loss; Noise-induced hearing loss (NIHL); Sensorineural Hearing Loss Heat shock proteins, , cochlear stress, 213 Heffner Harrington model, tinnitus, 121ff History, aminoglycosides as ototoxic drug, ARHL research, 146ff cisplatin as ototoxic drug, deafness, 1 2 ototoxic drugs, HLA-A2, Ménière s disease, 79 Homeostasis, 2ff, 49ff disorders, 49ff, 73ff free radicals, 50ff, 236 intracellular, 49ff pericellular, 60ff principles, 49 Human, animal models of genetic hearing loss, ARHL, 145ff Autoimmune Inner Ear Disorder, 131ff central auditory system and ARHL, drug-induced hearing loss, 219ff, 223ff noise-induced hearing loss, 195 peripheral aspects of ARHL, 149ff protection against aminoglycosides, 245 Huntington s disease, 36 Immune response, inner ear, 131ff Immunology, inner ear, 131ff Impulse noise, cell death, 211 Inferior colliculus, ARHL in animals, GABA changes with RHL, 167 physiological changes with ARHL, structural changes with ARHL, tinnitus, 111 Inner ear effects of aminoglycosides, effects of cisplatin, immune response, 131ff inducement of proliferation in epithelium, neurotrophic factors, 290ff protection from ototoxic drugs, repair of hair cells, 324ff stem cells, 329ff See also Cochlea Inner ear blood flow, effect of noise, Inner ear fluid, regulation, 66ff Inner hair cells effects of aminoglycosides, 231 pathology, See also Outer hair cells Ion channels, genes, Ionic homeostasis, Iron, aminoglycosides, 237 free, 52 homeostasis, 52 Jastreboff Brennan model, tinnitus, 116ff Jerker mouse, 36 Jervell Lange Nielsen syndrome, 70, JNK, apoptosis, apoptotic pathways, and aminoglycosides, apoptotic pathways and cisplatin, 240 apoptotic pathways and suppression by neurotrophic stimuli, 297 apoptotic regulators, protection from noise damage, 285 Kanamycin, see Aminoglycosides KCN (K + channels KCNE1, Jervell Lange Nielsen syndrome, KCNJ1, Bartter syndrome, 78 KCNJ10, 68, KCNMA1, 68 KCNN2, 68 KCNQ1, Jervell Lange Nielsen syndrome, KCNQ4, 28, 31, KHRI-3, autoimmune inner ear disease (AIED), Lifestyle, effect on ARHL, 176 LOC efferents, protection from excitotoxicity, 299 Math1, see Atoh1, 1hair cell regeneration Mechanical damage, sensorineural hearing loss, 258ff Medial olivary complex, efferents, protection against noise-induced, 286 Membrane depolarization, support of spiral ganglion neurons, 294ff

8 346 Index Ménière s disease, 70, 79ff and calcium, 79 emotional stress, 81 Methotrexate, treatment for autoimmune inner ear disease (AIED), 137 Mice, genes related to ARHL, models for aminoglycoside-induced hearing loss, models for ARHL, 158ff Mineralocorticoids, ARHL, 177, 178 MITF, 16 Mitochondria, apoptotic pathways, 209, , 277ff in aminoglycoside ototoxicity, , 287 in cisplatin ototoxicity, 241 clock theory and, ARHL, 173 free radical formation, 50, 172, 206, 235 inheritance, 11 involvement in protection from noise, 285 mutations and relationship to aminoglycoside ototoxicity, , 238 mutations and relationship to ARHL, 173, 287 mutations and relationship to cisplatin ototoxicity, in noise trauma, 206 Mixed ARHL, Mouse model, aminoglycoside ototoxicity, ARHL, 145, 158ff Mouse mutants, types, MRL-Fas mouse, autoimmune inner ear disease (AIED), 140 Myosins, 23ff Myosin IA (Myo1A), 23 Myosin IIIA (Myo3A), 23 Myosin VI (Myo6), 23, 24, 31, 34 Myosin VIIA (Myo7A), 18, 23, Myosin XV (Myo15), Myosin XVA (Myo15A), 23, 25 Necrosis, hair cells, 208ff see also Cell death Neomycin, see Aminoglycosides Nephrotoxicity, aminoglycosides, cisplatin, 223 Neural ARHL, animals, Neuronal apoptosis, 282 Neuronal trauma, excitotoxicity, Neurotransmitters, role in excitotoxciity, 107, 153, 199, 257, 299 role in synaptic reorganization, Neurotrophic factors, protection of hair cells from damage, protection of spiral ganglion neurons, , 302 support of spiral ganglion neurons, 290ff Neurotrophic stimuli, suppression of NJK signaling, 297 Neurotrophin receptor p75 NTR, 293 NF- B, aminoglycosides, 242, 281 in ARHL, regulation, 280 Nitric oxide, aminoglycosides, 238 cisplatin, 237 cochlear blood flow, 64, excitotoxicity, 299 redox homeostasis, 50ff, 236 NMDA receptors, tinnitus, 107 Noise, acoustic characteristics and resulting pathology, Noise exposure 4-kHz notch, 202 apoptosis, 287 cochlear nucleus pathology, 265 cochlear pathology, 195ff, 201ff effects on ARHL, 176 effects on ATP in ear, 289 effects on cochlear elements, 305 effects on inner ear blood flow, GABA and synaptic reorganization, growth factors and synaptic reorganization, 267 oxidative stress, 206ff stress responses, synaptic reorganization, temporary effects, 203 See also Acoustic Overstimulation, Acoustic Trauma, Noise-induced hearing loss (NIHL) Noise-induced hearing loss (NIHL), 195ff, 28 protection against, 284 protection by medial olivary complex efferents, 286 protection by neurotrophic factors, See also Acoustic Overstimulation, Acoustic Trauma, Noise exposure Non-syndromic hearing loss (NSHL), 13, 21ff Norepinephrine, potassium homeostasis, 70 NT-3, spiral ganglion neuron support, Organ of Corti reactivation of developmental program, 324ff See also Inner Ear, Hair cells

9 Index 347 Otoancorin, 29 Otoferlin, 14 Ototoxic drugs, 219ff aminoglycosides, cisplatin, free radicals, 235ff genetic susceptibility, 238 history, oxidative stress, 235ff pathways of cell death, 238ff protection of inner ear, Ototoxicity, animal models, incidence from aminoglycosides, incidence from cisplatin, 224 Ototoxins, effect on ARHL, 176 See also Ototoxic drugs OTSC, 21 Outer hair cells, 198 effects of aminoglycosides, 231 effects of cisplatin, loss with cisplatin, pathology, See also Hair cells Outer hair cell stereocilia, pathology, 197 Oxidative stress, 5, 211 aminoglycosides, cell injury, cisplatin, nitric oxide, 236, 237, 238 ototoxic drugs, 235ff See also Free Radicals; Redox Homeostasis p53 transcription factor, apoptosis, 283 Pathology, cochlear in ARHL, 149ff See also ARHL, Aminoglycsoides; Cisplatin, adverse side effects; Noise-induced hearing loss (NIHL) Pathophysiology, aminoglycosides, 229 cisplatin, 229 PAX3, 16 PCDH15, 18, 27, 29 PDS, Pendred syndrome, 19 20, 70, and calcium, 79 endolymph ph, 71 Pendrin, 29 Peptide neurotrophic factors, receptors, Perception, ARHL and peripheral effects, 168 effects of central auditory pathology, Pericellular homeostasis, 60ff Permanent threshold shift, 203 Pharmacokinetics, aminoglycosides, cisplatin, Pharmacology, ARHL prevention and treatment, Autoimmune Inner Ear Disorder treatment, 137 drug-induced hearing loss prevention and treatment, hearing loss prevention and treatment, 284ff tinnitus prevention and treatment, ph regulation, 55ff endolymph, 71 Pillar cells, pathology, 196ff Plasticity, central auditory system, 258ff Potassium, buffering, channels, See also KCN (K + channels cycling, cochlea, 66ff homeostasis in the cochlea, 66ff sound stimulation, 70 transport, 69 POU4f3, 33ff Preconditioning to prevent hearing loss, Presbycusis, 145ff origin of word, 146 See also Age-related hearing loss, ARHL Prestin, 32 Prevention, see Protection Proapoptotic gene expression, Programmed cell death, see Apoptosis, aminoglycosides Progressive hearing loss, definition, 10 Proliferation in inner ear epithelium, inducement, Prostaglandins, cochlear blood flow, Prosurvival genes, regulation of expression, Protection, against ARHL, 287 against free radicals, against hair cell death, 283ff against noise-induced hearing loss, 284 against ototoxic drugs, cochlear, 275ff role of blood flow in noise trauma, stress pathways, 280ff Protein function, methodologies, 31ff Protocadherin, 15, 27 Psychophysical methods, animal models for tinnitus, 116ff

10 348 Index R245X, 29 Reactive oxygen species, see Free Radicals; Oxidative Stress Redox homeostasis, 50ff free radical stress, 52 Redox imbalance, 50, 76 drug-induced 235ff Regeneration, see Hair Cell Regeneration Regrowth, spiral ganglion neurons, Renal Tubular Acidosis, Sensorineural Deafness Syndrome, Right ear advantage, ARHL, Risk factors, ARHL, 175ff aminoglycosides, cisplatin, genetic predisposition for ototoxicity, individual susceptibility to ototoxic drugs, 226 Romano Ward syndrome, 78 ROS (Reactive Oxygen Species), see Free Radicals; Oxidative Stress Salicylate, prevention of gentamicin-induced hearing loss, 245, 286 tinnitus, tinnitus animal models, 116ff SANS, Schedule-induced polydipsia method, tinnitus, Schuknecht, ARHL, 149, 155 Senile atrophy, 146 Sensorineural hearing loss categories, 322 cochlear trauma, 257ff from mechanical damage, 258ff See also Hearing Loss Sensory ARHL, 152, Shaker1 mouse, 18, Shaker2 mouse, 25 Signaling pathways, aminoglycoside-induced, 242 cell death, 276ff cell survival, 279ff central after SNHL, SIX1, 16 SLC (Solute Carrier) Family Proteins SLC1A3 (GLAST), 62 63, 75 SLC2A1 (GLUT1), 50 SLC2A5 (GLUT5), 50 SLC4A2 (AE2), SLC4A7 (NBC3), 57 SLC8A1 (NCX1), and calcium, SLC9A1 (NHE1), 57 SLC12A1 (NKCC2), Bartter syndrome, 78 SLC16A1 (MCT1), 50 SLC26A4 (pendrin), 19 20, 57, 76 77, 81 Small-molecule therapeutics, spiral ganglion protection, Small pox vaccinations, autoimmune inner ear disease (AIED), 141 SNAI2, 16 Snell s waltzer mouse, 24 Sound-gap inhibition of startle, tinnitus, 124 SOX10, 16 Speech perception, ARHL central pathology, 169 Speech processing, changes with age, 157 Spiral ganglion cells, degeneration, 138, 142, 152, 230, 263ff, 293, 298ff excitotoxicity, non-hair cell support, Spiral ganglion neurons, need for hair cells, neurotrophic factors, 290ff protection by antioxidants, 303 protection by neurotrophic factors, , 302 protection by small-molecule therapeutics, regrowth after trauma, support by calcium, support by electrical activity, 294ff survival and electrical stimulation, therapeutic intervention to protect, 300ff Spiral ligament. acid removal mechanisms, 57 AHRL in animals, , , 173 AHRL in human, 152, 155 Alport Syndrome, 21 cisplatin, 230, 233, 240 cochlear blood flow regulation, 64 cochlear fluid regulation, 66ff connexin, 23, 26, 74 noise, 198, 201 Pendred syndrome, 76 Spiral modiolar artery, Spontaneous activity, tinnitus, 108ff Stem cells, differentiation into hair cells, 331 embryonic, 333 inner ear, 329ff Stem cell therapy, 4ff challenges, Stereocilia ARHL and Cadherin, 23, 158 block of transduction channels by aminoglycosides, 235 cadherin mutations, 18, 26 27

11 Index 349 Myosin VIIa mutations, 18, Myosin XV mutations, pathology in human ARHL, 175 pathology in noise trauma, 197, 204 pathology in Shaker2, 24 pathology in Snell s waltzer, 24 pathology in tinnitus, 105, 107 regeneration, 332 Stereocilin, 29 Steroids, treatment for autoimmune inner ear disease (AIED), 137 Strategies for restoring cochlea Streptomycin, see Aminoglycosides Stress, see Free Radicals, Oxidative Stress Stress pathways, protection, 280ff Stria vascularis, 50ff acid removal mechanisms, 57 ARHL, ARHL in animals, degeneration, 76, 140, 141, 153, 154, 159, 161ff effects of cisplatin, 230 endocochlear potential, 66ff, 73ff, Supporting cells, AIED, , 141 ARHL, 153, 175 cisplatin, 230 cochlear regeneration, 325ff connexin-related deafness, fluid homeostasis, neurotrophins, 296 noise, 195ff, 203 response to ATP, 289 transdifferentiation in basilar papilla, 323 transdifferentiation in vestibular structures, 324 Synapses, ARHL and inferior colliculus, 167 changes in AVCN with ARHL, 165 Synaptic reorganization, following noise exposure, Syndromic hearing impairment, 13ff Tectorin, 14 Temporal processing, ARHL central pathology, 169 Temporary effects, noise-induced hearing loss, 203 Terminal degeneration, cochlear nucleus, 258ff following acoustic overstimulation, 265 Therapeutic action, aminoglycosides, 222 cisplatin, 222 Therapeutic intervention, protection of hair cells, 283ff spiral ganglion neurons, 300ff See also Protection, against ARHL Tinnitus, 3ff, 101ff age-related, 103 animal models, 104ff auditory cortex, 111ff auditory nerve sites, 108ff DCN, 108ff demographics, 102 history, inferior colliculus, 111 mechanisms, 105ff noise-induced, 103 pharmacologic interventions, treatment principles, 113ff types, 102ff Tmc1, 31 TMPRSS3, 29 Transcranial magnetic stimulation (TMS), tinnitus, 112 Transcriptional regulation, apoptosis and cell survival, 278ff Transduction, in cochlea, 67 adaptation and calcium, 79 Transient hearing loss, definition, 10 Transients of high level noise, Transport mechanisms into cells aminoglycosides, energy metabolites, 50 ions, 53ff Trauma, 321ff See also, Acoustic Overstimulation; Acoustic Trauma; Aminoglycosides; Cisplatin; Drug-Induced hearing loss; Noise exposure; Noise-induced hearing loss (NIHL) Treatment, see Antioxidant therapy; Pharmacology; Therapeutic intervention TRIOBP, Tropomyosin, CBF, UB/OC2 cells, 33 Usher syndrome, 17ff USH1, 17 USH1B, 18 USH1C, 18 USH1D, 18, 26 USH1F, 18, 27 USH2, 17 USH2A, 19 USH3, 17, 32 Vasodilation and vasoconstriction, cochlea, 64

12 350 Index Vertigo, see Vestibular dysfunction Vestibular dysfunction, AIED, 134 aminoglycosides, 224 Cogan s syndrome, 141 Ménière s disease, 79 Usher syndrome, 17 Vestibular endolymph, 78, 81 Vestibular system, aminoglycoside pathology, 231, 232 cisplatin pathology, endolymph, 78, 81 hair cells, regeneration, 324 potassium cycling, 69 stem cells, Waardenburg syndrome (WS), types, W altzer mouse, 18 Whirlin, 29

13 Springer Handbook of Auditory Research (continued from page ii) Volume 22: Evolution of the Vertebrate Auditory System Edited by Geoffrey A. Manley, Arthur N. Popper, and Richard R. Fay Volume 23: Plasticity of the Auditory System Edited by Thomas N. Parks, Edwin W. Rubel, Arthur N. Popper, and Richard R. Fay Volume 24: Pitch: Neural Coding and Perception Edited by Christopher J. Plack, Andrew J. Oxenham, Richard R. Fay, and Arthur N. Popper Volume 25: Sound Source Localization Edited by Arthur N. Popper and Richard R. Fay Volume 26: Development of the Inner Ear Edited by Matthew W. Kelley, Doris K. Wu, Arthur N. Popper, and Richard R. Fay Volume 27: Vertebrate Hair Cells Edited by Ruth Anne Eatock, Richard R. Fay, and Arthur N. Popper Volume 28: Hearing and Sound Communication in Amphibians Edited by Peter M. Narins, Albert S. Feng, Richard R. Fay, and Arthur N. Popper Volume 29: Auditory Perception of Sound Sources Edited by William A. Yost, Arthur N. Popper and Richard R. Fay Volume 30: Active Processes and Otoacoustic Emissions in Hearing Edited by Geoffrey A. Manely, Arthur N. Popper and Richard R. Fay Volume 31: Auditory Trauma, Protection, and Repair Edited by Jochen Schacht, Arthur N. Popper and Richard R. Fay For more information about the series, please visit