Учебники / Auditory Trauma, Protection, and Repair Fay 2008

Deaf-waddler mouse, 72–73

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, 169–170

Eighth nerve, ARHL, 152–153

Index 343

Electrical stimulation, protection of spiral ganglion neurons, 301–302

Embryonic stem cells, 333

Emotional stress, Ménière’s disease, 81 Endocochlear potential, aminoglycosides, 229

ARHL, 153–154, 159 ARHL in animals, 161–163 BALB mice, 162–163 cisplatin, 229

melanocytes, 15 mice, 162–163 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, 202–203 leakage in Ménière’s disease, 298–299 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), 133–134

Energy metabolism, 50ff ENU mutagenesis, 30–31

Environmental factors, effect on ARHL, 175ff Epinephrine, potassium homeostasis, 70 Excitotoxicity, as neuronal trauma, 298–299

cochlea, 298–299 hair cells, 199

intracellular mediators of, 299 protection from by LOC efferents, 299 spiral ganglion cells, 298–299

EYA1, 16

Fiber degeneration

following acoustic overstimulation, 263–265 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, 164–165

FK506, and protection of hair cells, 210–211

344 Index

FOX1, mouse model, 81 Free radicals, 5

aminoglycosides, 237–238 apoptosis, 281

cisplatin, 236–237 cochlea, 236–237 ototoxic drugs, 235ff

protection by antioxidants, 52–53, 284, 286–287

protection of hair cells, 284–285 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, 113–114 ARHL in inferior colliculus, 167

synaptic reorganization following noise exposure, 266–267

Gap coding, changes in CBA mice with age, 167–168

Gap junction proteins, 22ff endocochlear potential, 75 GJA1 (Cx43), 75–76 GJA7 (Cx45), 76

GJB2 (Cx26), 74–75 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, 146–148

Gene identification, methodology, 28ff Genes, ARHL in mice, 158–159

hair cell proliferation, 327–328

Genetic factors, aminoglycoside ototoxicity, 226–227

cisplatin ototoxicity, 225–226 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, 327–328 Hair cell regeneration, 4, 321ff

Atoh1, 326–327

basilar papilla, 323–324 bHLH gene, 326

birds, 323–324

challenges to treatment, 332 differentiation of hair cells from stem

cells, 331 mammals, 324

molecular control, 323–324 nonmammalian vertebrates, 322

reactivation of developmental programs, 324ff use of cochlear nonsensory cells, 325–327 use of supporting cells, 326–327

vestibular system, 324 Hair cells

aminoglycoside uptake, 233–234 ARHL, 151–152

death pathways, 208ff differentiation from stem cells, 331

effect of cisplatin, 227–228, 229–231 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,

290–291

therapeutic intervention, 283ff

See also Inner hair cells; Outer hair cells Hair cell transduction, pathology, 198ff Harmonin b, 26–27

Hearing loss

aging humans, 146ff ahl genes, 158

aminoglycosides, 224–225 categories, 10

causes, 3ff, 322 cell death, 275ff

challenges to treatment, 332 cisplatin, 227–228 drug-induced, 219ff genetic, 288

ototoxicity, 219ff

pathophysiology from ototoxic drugs, 229 preconditioning of protective mechanisms,

288–290

restoration in ARHL, 181–182

See also Age-related Hearing Loss; Drug-induced hearing loss; Noise-induced hearing loss (NIHL); Sensorineural Hearing Loss

Heat shock proteins, 280–281, 288–289 cochlear stress, 213

Heffner–Harrington model, tinnitus, 121ff History, aminoglycosides as ototoxic drug,

221–222

ARHL research, 146ff

cisplatin as ototoxic drug, 221–222 deafness, 1–2

ototoxic drugs, 220–222 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, 30–31

ARHL, 145ff

Autoimmune Inner Ear Disorder, 131ff central auditory system and ARHL,

155–157

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, 166–168 GABA changes with RHL, 167 physiological changes with ARHL, 166–167 structural changes with ARHL, 166–167 tinnitus, 111

Inner ear

effects of aminoglycosides, 233–234 effects of cisplatin, 232–233 immune response, 131ff

inducement of proliferation in epithelium, 327–328

neurotrophic factors, 290ff

protection from ototoxic drugs, 243–245 repair of hair cells, 324ff

Index 345

stem cells, 329ff

See also Cochlea

Inner ear blood flow, 304–305 effect of noise, 304–305

Inner ear fluid, regulation, 66ff Inner hair cells

effects of aminoglycosides, 231 pathology, 195–196

See also Outer hair cells Ion channels, 27–28

genes, 27–28

Ionic homeostasis, 53–54 Iron, aminoglycosides, 237

free, 52 homeostasis, 52

Jastreboff–Brennan model, tinnitus, 116ff Jerker mouse, 36

Jervell Lange–Nielsen syndrome, 70, 77–78 JNK, apoptosis, 282–283

apoptotic pathways, and aminoglycosides, 241–242

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, 77–78

KCNJ1, Bartter syndrome, 78 KCNJ10, 68, 76–77 KCNMA1, 68

KCNN2, 68

KCNQ1, Jervell–Lange–Nielsen syndrome, 77–78

KCNQ4, 28, 31, 67–68

KHRI-3, autoimmune inner ear disease (AIED), 139–140

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

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, 158–159 models for aminoglycoside-induced hearing

loss, 228–229 models for ARHL, 158ff

Mineralocorticoids, ARHL, 177, 178 MITF, 16

Mitochondria, apoptotic pathways, 209, 238–239, 277ff

in aminoglycoside ototoxicity, 238–239, 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, 226–227, 238 mutations and relationship to ARHL,

173, 287

mutations and relationship to cisplatin ototoxicity, 225–226

in noise trauma, 206 Mixed ARHL, 154–155

Mouse model, aminoglycoside ototoxicity, 228–229

ARHL, 145, 158ff

Mouse mutants, types, 30–31

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, 24–25 Myosin XV (Myo15), 25–26

Myosin XVA (Myo15A), 23, 25

Necrosis, hair cells, 208ff see also Cell death

Neomycin, see Aminoglycosides Nephrotoxicity, aminoglycosides, 223–224

cisplatin, 223

Neural ARHL, 152–153 animals, 161–163 Neuronal apoptosis, 282

Neuronal trauma, excitotoxicity, 298–299 Neurotransmitters, role in excitotoxciity, 107,

153, 199, 257, 299

role in synaptic reorganization, 266–267

Neurotrophic factors, protection of hair cells from damage, 285–286

protection of spiral ganglion neurons, 300–301, 302

support of spiral ganglion neurons, 290ff Neurotrophic stimuli, suppression of NJK

signaling, 297

Neurotrophin receptor p75NTR , 293 NF- B, aminoglycosides, 242, 281

in ARHL, 160–161 regulation, 280

Nitric oxide, aminoglycosides, 238 cisplatin, 237

cochlear blood flow, 64, 200–201 excitotoxicity, 299

redox homeostasis, 50ff, 236 NMDA receptors, tinnitus, 107

Noise, acoustic characteristics and resulting pathology, 201–202

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, 304–305 GABA and synaptic reorganization,

266–267

growth factors and synaptic reorganization, 267

oxidative stress, 206ff stress responses, 211–212

synaptic reorganization, 266–267 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, 285–286 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,

291–292

Organ of Corti

reactivation of developmental program, 324ff See also Inner Ear, Hair cells

Otoancorin, 29

Otoferlin, 14 Ototoxic drugs, 219ff

aminoglycosides, 221–222 cisplatin, 220–221

free radicals, 235ff genetic susceptibility, 238 history, 220–222 oxidative stress, 235ff

pathways of cell death, 238ff protection of inner ear, 243–245

Ototoxicity, animal models, 227–229 incidence from aminoglycosides,

224–225

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, 229–231 loss with cisplatin, 227–228 pathology, 195–196

See also Hair cells

Outer hair cell stereocilia, pathology, 197 Oxidative stress, 5, 211

aminoglycosides, 237–238 cell injury, 172–173 cisplatin, 236–237

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, 19–20

Pendred syndrome, 19–20, 70, 76–77 and calcium, 79

endolymph pH, 71 Pendrin, 29

Peptide neurotrophic factors, receptors, 292–293

Perception, ARHL and peripheral effects, 168 effects of central auditory pathology,

169–171

Pericellular homeostasis, 60ff Permanent threshold shift, 203

Index 347

Pharmacokinetics, aminoglycosides, 233–234 cisplatin, 232–233

Pharmacology, ARHL prevention and treatment, 180–181

Autoimmune Inner Ear Disorder treatment, 137

drug-induced hearing loss prevention and treatment, 243–245

hearing loss prevention and treatment, 284ff

tinnitus prevention and treatment, 113–114 pH regulation, 55ff

endolymph, 71

Pillar cells, pathology, 196ff

Plasticity, central auditory system, 258ff Potassium, buffering, 60–61

channels, 60–61

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, 288–290

Presbycusis, 145ff origin of word, 146

See also Age-related hearing loss, ARHL Prestin, 32

Prevention, see Protection Proapoptotic gene expression, 281–282 Programmed cell death, see Apoptosis,

aminoglycosides

Progressive hearing loss, definition, 10 Proliferation in inner ear epithelium,

inducement, 327–328 Prostaglandins, cochlear blood flow,

200–201

Prosurvival genes, regulation of expression, 279–280

Protection, against ARHL, 287 against free radicals, 284–285 against hair cell death, 283ff

against noise-induced hearing loss, 284 against ototoxic drugs, 243–245 cochlear, 275ff

role of blood flow in noise trauma, 304–305

stress pathways, 280ff

Protein function, methodologies, 31ff Protocadherin, 15, 27

Psychophysical methods, animal models for tinnitus, 116ff

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, 303–304 Renal Tubular Acidosis, Sensorineural

Deafness Syndrome, 78–79 Right ear advantage, ARHL, 170–171 Risk factors, ARHL, 175ff

aminoglycosides, 225–226 cisplatin, 225–226

genetic predisposition for ototoxicity, 225–227

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, 111–112

tinnitus animal models, 116ff SANS, 18–19

Schedule-induced polydipsia method, tinnitus, 123–124

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, 158–159 Shaker1 mouse, 18, 24–25 Shaker2 mouse, 25

Signaling pathways, aminoglycoside-induced, 242

cell death, 276ff cell survival, 279ff

central after SNHL, 262–263 SIX1, 16

SLC (Solute Carrier) Family Proteins

SLC1A3 (GLAST), 62–63, 75 SLC2A1 (GLUT1), 50 SLC2A5 (GLUT5), 50 SLC4A2 (AE2), 57–58 SLC4A7 (NBC3), 57

SLC8A1 (NCX1), and calcium, 59–60 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, 302–303

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, 298–299 non-hair cell support, 297–298

Spiral ganglion neurons, need for hair cells, 290–291

neurotrophic factors, 290ff protection by antioxidants, 303

protection by neurotrophic factors, 300–301, 302

protection by small-molecule therapeutics, 302–303

regrowth after trauma, 303–304 support by calcium, 295–297 support by electrical activity, 294ff survival and electrical stimulation,

301–302

therapeutic intervention to protect, 300ff Spiral ligament. acid removal mechanisms, 57 AHRL in animals, 158–159, 162–163, 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, 63–64 Spontaneous activity, tinnitus, 108ff

Stem cells, differentiation into hair cells, 331 embryonic, 333

inner ear, 329ff Stem cell therapy, 4ff

challenges, 332–333 Stereocilia

ARHL and Cadherin, 23, 158 block of transduction channels by

aminoglycosides, 235 cadherin mutations, 18, 26–27

Myosin VIIa mutations, 18, 24–25 Myosin XV mutations, 25–26 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, 153–154

ARHL in animals, 161–163

degeneration, 76, 140, 141, 153, 154, 159, 161ff

effects of cisplatin, 230 endocochlear potential, 66ff, 73ff,

153–154

Supporting cells, AIED, 139–140, 141 ARHL, 153, 175

cisplatin, 230

cochlear regeneration, 325ff connexin-related deafness, 74–75 fluid homeostasis, 68–69 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, 266–267

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

Index 349

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, 101–102

inferior colliculus, 111 mechanisms, 105ff noise-induced, 103

pharmacologic interventions, 113–114 treatment principles, 113ff

types, 102ff

T mc1, 31

T MPRSS3, 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, 202–203 Transport mechanisms into cells

aminoglycosides, 233–234 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

T RIOBP, 29–30 Tropomyosin, CBF, 200–201

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

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, 231–232

endolymph, 78, 81

hair cells, regeneration, 324 potassium cycling, 69

stem cells, 329–330

Waardenburg syndrome (WS), 15–16 types, 15–16

W altzer mouse, 18 Whirlin, 29