Hearing Loss: Mechanisms, Prevention and Cure (eBook)

Dr. Huawei Li, M.D. is a Professor, Chief Physician and doctoral and post doctoral mentor, and was appointed Chairman of the Department of Otorhinolaryngology Affiliated Eye and ENT Hospital in 2016. His other appointments include Vice-chairman of NHC Key Laboratory of Hearing Medicine, President of the Shanghai Otolaryngology Doctors’ Association, Vice-president of Shanghai Medical Association of Otolaryngology Head and Neck Surgey, member of the Chinese Medical Association of Otolaryngology Head and Neck Surgery. He is also Chief Scientist of 973 National Project of China and of the National Key R&D Program of China, Specially-appointed Professor in the Yangtze River Scholar Program, Laureate of National Outstanding Youth Science Fund, Shanghai Excellent Discipline Leaders, Visiting Professor of Massachusetts Eye and Ear Infirmary, Harvard Medical School. He has also received an honorary title for his outstanding contribution to NHC. His research focuses on otomicrosurgery, stem cell transcriptional regulation, and hair cell regeneration. He has published more than 100 papers, including in Nature Medicine and PNAS. Dr. Renjie Chai, Ph.D., is a Professor and Assistant Dean of the Institute of Life Sciences, Southeast University. His other appointments include Vice-president of the Association of Hearing, Speech and Communication in Biophysical Society of China, executive board member of the International Association of Physicians in Audiology. He is the winner of the National Natural Science Foundation of China Excellent Youth Fund and of the 1000 Young Talents Recruitment Plan of China, and has been awarded more than 20 grants including the National Key R&D Program of China, the Strategic Priority Research Program of the Chinese Academy of Science, and a Faculty Research Award from Boehringer Ingelheim and Novartis. His research focuses on the regeneration and protection of inner ear hair cells and spiral ganglion neurons. He has published more than 70 papers, including in Advanced Materials, Nature Communications, and PNAS.

Contents 6
Chapter 1: Hair Cell Regeneration 7
1.1 History of Hair Cell Regeneration 8
1.2 Methods Used in Hair Cell Regeneration 9
1.2.1 Method for Lineage Tracing of Specific Gene (e.g., X) Positive Inner Ear Stem Cells 9
1.2.2 Method for Sorting EGFP-Positive Cochlear Stem Cells Using Flow Cytometry 9
1.2.3 Culture of Cochlear Stem Cells In Vitro and Methods for Detecting Their Proliferation and Differentiation 9
1.2.4 Method for In Vitro Culture of Cell Spheres After Flow Cytometry Sorting of Cochlear Stem Cells 9
1.3 Inner Ear Stem Cells 10
1.3.1 Inner Ear Supporting Cells as Precursor Cells 10
1.3.2 Supporting Cell Subtypes 10
1.4 Transcription Factor Regulation of Inner Ear Stem Cells 11
1.5 Signaling Pathways That Regulate Inner Ear Stem Cells and Hair Cell Regeneration 13
1.5.1 The Wnt Signaling Pathway in Auditory Hair Cell Development and Regeneration 13
1.5.2 The Notch Signaling Pathway in Auditory Hair Cell Regeneration 14
1.5.3 The Hedgehog Signaling Pathway in Auditory Hair Cell Regeneration 15
1.5.4 The FGF Signaling Pathway in Hair Cell Regeneration 15
1.6 Epigenetic Regulation in Hair Cell Regeneration 16
1.7 Ribbon Synapse Re-formation in Regenerated Mammalian Hair Cells 17
1.8 Hearing Function Recovery 17
1.8.1 Hearing Function Recovery in the Avian Vestibular and Cochlear System 17
1.8.2 Hearing Function Recovery in the Mammalian Inner Ear 18
1.9 Brake and Future Directions 18
References 19
Chapter 2: Protection of Hair Cells from Ototoxic Drug-Induced Hearing Loss 23
2.1 Introduction 24
2.2 Definitions of Ototoxic Drugs 24
2.3 Genetic Mechanisms of Ototoxic Drug-Induced Hearing Loss 25
2.4 Classification of Ototoxic Drugs 27
2.4.1 Antibiotics 27
2.4.2 Nonantibiotics 28
2.5 Metabolism of Ototoxic Drugs in the Inner Ear 29
2.6 Research Progress and the Mechanisms of Ototoxic Drugs 31
2.6.1 Membrane-Dependent Ototoxicity 31
2.6.2 Cytoplasm-Dependent Ototoxicity 32
2.6.3 Nucleus-Dependent Ototoxicity 33
2.7 Approaches for Minimizing Ototoxicity 33
2.7.1 Prevention 34
2.7.2 Treatment 34
2.8 Development of Small Molecules for Hair Cell Protection 36
2.9 Conclusion 37
References 37
Chapter 3: Noise-Induced Cochlear Synaptopathy and Ribbon Synapse Regeneration: Repair Process and Therapeutic Target 43
3.1 Introduction 44
3.2 Anatomic and Functional Features of Cochlear Ribbon Synapse 44
3.3 Synaptic Damage by Noise 46
3.3.1 Potential Mechanisms 46
3.3.2 Selective Damage to Synapses with Low Spontaneous Rate Units 47
3.3.3 Can the Disrupted Ribbon Synapse Be Rebuilt? 49
3.4 Synaptic Protection and Regeneration in Noise-Induced Synaptopathy 50
3.4.1 Synapse Protection 50
3.4.2 Synapse Regeneration 51
3.5 Conclusion and Future Direction 57
References 57
Chapter 4: Protection and Prevention of Age-Related Hearing Loss 64
4.1 Introduction 64
4.2 The Etiology of Age-Related Hearing Loss 65
4.2.1 External Environmental Factors 65
4.2.2 Vascular Disease in the Inner Ear 66
4.2.3 Changes of Neurotransmitters and Neuroactive Substances 66
4.2.4 Diet and Related Factors 67
4.2.5 Related Gene Mutation 67
4.2.6 Epigenetic Changes 67
4.2.7 Other Factors 67
4.3 The Pathology of Age-Related Hearing Loss 69
4.4 Clinical Symptom and Diagnosis of Age-Related Hearing Loss 70
4.4.1 Clinical Manifestation 70
4.4.2 Examination Method and Diagnosis 70
4.5 Prevention and Treatment of Age-Related Hearing Loss 73
4.6 Conclusion 74
References 74
Chapter 5: Diagnosis, Intervention, and Prevention of Genetic Hearing Loss 77
5.1 Introduction of Deafness Genes 78
5.1.1 The Gap Junctions 78
5.1.2 Tight Junction Proteins 79
5.1.3 The Cytoskeleton 79
5.1.4 Transmembrane Proteins 80
5.1.5 Transcription Factors 81
5.1.6 microRNAs 82
5.2 Genetic Screening and Diagnosis of Hearing Loss 82
5.2.1 Genetic Diagnosis 82
5.2.2 Sanger Sequencing 83
5.2.3 Next-Generation Sequencing 84
5.2.4 Genetic Screening 85
5.3 Intervention and Prevention of Genetic Hearing Loss 87
5.3.1 Gene Therapy 87
5.3.1.1 Design of Gene Therapy for HL 87
5.3.1.2 Vectors 88
5.3.2 Genetic Implications for Cochlear Implantation 89
5.3.3 Prevention of Genetic Hearing Loss 89
References 90
Chapter 6: Protection of Spiral Ganglion Neurons and Prevention of Auditory Neuropathy 97
6.1 Introduction 97
6.2 The Spiral Ganglion: Connecting the Peripheral and Central Auditory Systems 98
6.3 Mechanisms of Cochlear Neuronal Damage 99
6.4 Repair and Protection of Spiral Ganglion Neuron 102
6.5 Neural and Synaptic Mechanisms of Auditory Neuropathy 103
6.6 Current Options for Hearing Rehabilitation from Auditory Neuropathy 105
6.7 Conclusion 106
References 107
Chapter 7: Advances in Understanding, Diagnosis, and Treatment of Tinnitus 112
7.1 Introduction 113
7.2 Epidemics 114
7.3 Hearing Loss and Tinnitus 115
7.3.1 The Tonotopic Reorganization Model 115
7.3.2 The Neural Synchrony Model 116
7.3.3 The “Hidden Hearing Loss” Hypothesis 117
7.4 Neural Basis of Tinnitus 118
7.5 Diagnosis 118
7.5.1 Subjective Report 119
7.5.2 Objective Assessment 119
7.5.2.1 Audiometry Examination 119
7.5.2.2 Tinnitus Matching 120
7.6 Treatment 121
7.6.1 Cognitive Behavioral Therapy 121
7.6.2 Masking Devices 122
7.6.3 Sound Therapy 124
7.6.4 Biofeedback Therapy 125
7.6.5 Medications and Alternative Medicine 126
7.7 Summary 126
References 127
Chapter 8: Cochlear Implantation and Rehabilitation 132
8.1 Background of Cochlear Implants 132
8.2 Design of Cochlear Implants 134
8.3 Indications 136
8.4 Preoperative Evaluation 138
8.5 Surgical Approaches 140
8.6 Surgical Complications 143
8.7 Outcome Expectations 143
References 144
Chapter 9: Non-implantable Artificial Hearing Technology 148
9.1 Introduction 149
9.2 History of Hearing Aids 149
9.2.1 Sound Collector Era 149
9.2.2 Carbon Era 149
9.2.3 Vacuum Tube Era 150
9.2.4 Transistor and Integrated Circuit Era 150
9.2.5 Digital Era 150
9.3 How Hearing Aids Work 151
9.3.1 Microphone 151
9.3.2 Amplifier 152
9.3.3 Receiver (Earpiece) 152
9.3.4 Battery 152
9.3.5 Function Adjustment Knob of Hearing Aids 152
9.3.6 Auditory Auxiliary Components 152
9.4 Types and Characteristics of Hearing Aids 153
9.4.1 Pocket Hearing Aids 153
9.4.2 BTE Hearing Aids 154
9.4.3 ITE Hearing Aids 154
9.4.4 In-the-Canal Hearing Aids (ITC) 155
9.4.5 Completely/Invisible-in-Canal Hearing Aids (CIC and IIC) 156
9.4.6 Other Types 156
9.5 Bone-Anchored Hearing Aid Softband 156
9.5.1 BAHA System Components 157
9.5.2 Indication 158
9.6 Selection of Hearing Aids 159
9.6.1 Fitting Formulas of Hearing Aids 159
9.6.2 Real Ear Measurement (REM) 160
9.6.3 Hearing Aid Fitting 160
9.7 Fitting Considerations for Children and Seniors 161
9.7.1 Hearing Aid Fitting for Children [18] 161
9.7.2 Hearing Aid Fitting for Seniors [19] 162
9.8 Evaluation for Rehabilitation and Benefits 163
9.8.1 Preliminary Evaluation 163
9.8.2 Mid-stage Evaluation 164
9.8.3 Regular Follow-Up 165
9.8.4 Influence of Hearing Aids on Health and Life Quality 165
References 165
Chapter 10: Stem Cells: A New Hope for Hearing Loss Therapy 167
10.1 Introduction 168
10.2 Endogenous Stem Cell 168
10.3 Exogenous Stem Cells 171
10.4 Cell Transplantation Approaches 173
10.5 Cochlear Internal Environmental Factors and External Stimulation Factors 174
10.6 Functional Restoration of Hearing 177
10.7 Challenges and Perspectives 177
References 178