Handbook of Neural Engineering

Contributors xiii<br>Preface xix<br>Acknowledgments xxi<br>1. Introduction to neural engineering 1<br>Stephanie Willerth<br>1 Introduction 1<br>2 Biomedical engineering and the evolution of neural engineering 5<br>3 Biological considerations for neural engineering 7<br>4 Neural engineering strategies 10<br>5 Emerging technologies for neural engineering 11<br>6 Conclusions 13<br>References 13<br>SECTION 1 Biological considerations for neural engineering<br>2. Overview of the structure and function of the nervous system 17<br>1 Introduction 17<br>2 Early development of the nervous system 18<br>3 Functional anatomy of the CNS 21<br>4 Cell types 26<br>5 Neuronal communication 32<br>6 Summary and conclusions 41<br>References 41<br>3. Cellular biology of the central nervous system 49<br>1 Introduction 49<br>2 Neurons 49<br>3 Astrocytes 60<br>4 Microglia 66<br>5 Oligodendrocytes 72<br>6 Summary and conclusions 78<br>References 78<br>4. Extracellular matrix of the nervous system 97<br>1 Introduction 99<br>2 Composition and assembly of ECM in the nervous system 100<br>3 ECM during brain development 108<br>4 Neural ECM in aging and disease 115<br>5 Engineering ECM for human brain tissue models 120<br>6 Summary 130<br>References 131<br>5. The immune system and its role in the nervous system 149<br>1 Introduction 149<br>2 Overview of the immune system 150<br>3 Immunology within the nervous system 153<br>4 Interactions between the nervous system and the systemic<br>immune system 158<br>5 Neuroimmunity in injury, disease, and aging 159<br>6 Methods in neuroimmunology 162<br>7 Neuroimmune engineering 165<br>8 Conclusion 171<br>References 171<br>6. Modulating disease states of the central nervous system:<br>Outcomes of neuromodulation on microglia 179<br>1 Introduction 179<br>2 CNS seen from the microglial angle 183<br>3 Memory disorders 187<br>4 Disorders of inhibition 194<br>5 Disorders of consciousness and coma 203<br>6 Challenges and limitations of the techniques 212<br>7 Conclusion 213<br>References 214<br>7. The effect of traumatic injuries on the nervous system 231<br>1 Traumatic brain injury: Context and definitions 231<br>2 Primary injury and the onset of traumatic brain injury pathophysiology 234<br>3 The continuum of secondary injury 237<br>4 Acute phase 237<br>5 Subacute phase 248<br>6 Chronic phase 250<br>7 Repetitive TBI 253<br>8 Future directions in neurotrauma research 255<br>References 258<br>8. Chronic pain as a neurological disease and neural engineering strategies for its management 271<br>1 Pain is a protective mechanism necessary for survival 271<br>2 The nociceptive pain circuit 271<br>3 Chronic pain is a disease in its own right 284<br>4 Neuromodulation as an engineering approach in managing chronic pain 289<br>5 Conclusions 293<br>Acknowledgment 293<br>References 293<br>SECTION 2 Neural engineering strategies<br>9. An overview of noninvasive imaging strategies in neural engineering 301<br>1 Introduction 301<br>2 Utility of imaging modalities to neural engineering 303<br>3 Optical imaging 304<br>4 Ultrasound (US) 313<br>5 Magnetic resonance imaging (MRI) 315<br>6 X-rays and computed tomography (CT) 326<br>7 Positron emission tomography (PET) and single photon emission computed tomography (SPECT) 329<br>8 Electroencephalogram/magnetoencephalography (EEG/MEG) 333<br>9 Conclusions 335<br>References 335<br>10. Brain-computer interface 351<br>1 Defining brain-computer interface 351<br>2 History of BCI 354<br>3 Innovations in modern-day BCIS 357<br>4 Brief introduction to the nervous system 359<br>5 BCI types 360<br>6 BCI components 365<br>7 BCI applications 374<br>8 Challenges and future direction 378<br>References 380<br>11. Neuroprosthetics 389<br>1 Auditory prosthesis 389<br>2 Deep brain stimulation 394<br>3 Spinal cord neuroprosthetics 396<br>4 Neuromuscular prosthetics 398<br>5 Neuroprosthetics for internal organs 400<br>6 Outlook: The next generation of neuroprosthetics 404<br>References 406<br>12. Neural tissue engineering 413<br>1 Functional bio/nanomaterials 415<br>2 In vitro 3D tissue culture platforms for nervous system (spheroids and organoids) 430<br>3 Microfluidic systems 439<br>4 Scaffolding (implantable neural interfaces) 444<br>5 Electrical stimulations 452<br>6 Summary 457<br>References 459<br>SECTION 3 Emerging technologies for neural engineering<br>13. Optogenetics for neural tissue engineering applications 479<br>1 Biophysics of microbial rhodopsin 479<br>2 Diversity of optogenetic channels, pumps, and receptors 483<br>3 Use of light-sensitive proteins to manipulate intracellular signaling and metabolism 485<br>4 Visualization of cell activity 488<br>5 Optogenetics in biological systems 491<br>6 Optogenetics in medical applications 493<br>7 Future aims in optogenetic engineering 498<br>References 499<br>14. Neuroengineering: History, modeling, and deliverables 505<br>1 History of genomic editing 505<br>2 Neuronal cell models 510<br>3 In vivo models and applications of delivery 523<br>References 534<br>15. Recent developments in 3D bioprinting for neural tissue engineering 549<br>1 Overview of modeling neural tissue: From 2D and<br>3D culture systems to 3D bioprinting 549<br>2 How 3D bioprinting works 557<br>3 Design of biomaterial-based bioinks to mimic the neural microenvironment 561<br>4 3D bioprinted models for studying neurodegenerative diseases 576<br>5 Conclusion 579<br>References 579<br>16. Maximizing the utility of brain organoid models and overcoming their perceived limitations 593<br>1 Introduction 593<br>2 Current methods for generating brain organoids 595<br>3 Uses of brain organoids 613<br>4 Ethical considerations and limitations to data interpretation 616<br>5 Perspective and summary 616<br>References 617<br>17. Modeling the synapse and neuromuscular junction using organ-on-a-chip technology 625<br>1 Introduction 625<br>2 Synapse- and NMJ-on-a-chip: Design and fabrication 630<br>3 Applications of synapse and NMJ chips 633<br>4 Challenges and future directions 637<br>Acknowledgments 639<br>References 639<br>Index 645