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ICP2006年Neuroscience for Neurologists
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Contributors v Preface xi 1 Neurogenetics — Single Gene Disorders 1 Genetic Linkage Analysis 3 Linkage Disequilibrium and Association 3 Mutational Spectrum 5 Molecular Genetic Tools 6 Molecular Genetic Testing 9 Animal Models 11 Web-based Information for Genetic Diagnosis and Testing 13 Outlook 15 Acknowledgements 16 References 16 2 Neurogenetics II: Complex Disorders 19 Guiding Principles 21 Applications to Clinical Neurology 27 Tauopathies 31 New Technologies 35 Conclusions 38 Appendix A 38 Human Genetic Variation 38 Appendix B 39 Genetic Linkage and Association Analyses 39 References 40 XIII xiv Contents 3 Functional Genomics and Proteomics: Application in Neurosciences 45 Functional Genomics 46 RNA Preparation 47 Differential Display 48 SAGE 49 Microarrays 49 Real Time Q-PCR 53 Proteomics 55 Two Dimensional Gel Electrophoresis 56 ICAT — Isotope Coded Affinity Tags 59 Protein Microarrays 61 Mass Spectrometry 64 SELDI 67 Future Prospects 68 Acknowledgements 69 References 69 4 Mitochondria 77 Historical Introduction 77 What are Mitochondria and What Do They Do? 79 The Genetic Basis of Mitochondrial Biogenesis 81 Mitochondrial Disease: Genotype and Phenotype 83 Mitochondrial Genetic Factors 89 Confirming Suspected Mitochondrial Disease 94 Managing Mitochondrial Disease — The Future Animal Models 100 Conclusion 101 Acknowledgements 105 References 105 5 Nanotechnology for Neuronal Ion Channels 113 Channels — Essential for Neuronal Excitability 114 History of the Voltage Clamp Technique 114 Application to Clinical Neurology 120 Contents xv Principles Behind the Techniques 127 Potential Application of the Technologies in the Future 132 Conclusions 137 Acknowledgements 137 Appendix 1 137 Glossary of Terms 137 Appendix 2 139 Associated Websites of Interest 139 References 140 6 Molecular and Cellular Pathways of Neurodegeneration in Motor Neurone Disease 143 What Do We Know about the Causes of Motor Neurone Degeneration? 145 Genetics of ALS/MND 146 Oxidative Stress 156 Exci to toxicity 157 Mitochondrial Dysfunction 158 Cytoskeletal Elements and Axonal Transport 160 Protein Aggregation 161 Inflammatory Cascades and the Role of Non-Neuronal Cells 162 Apoptosis 164 Cell Specific Features of Motor Neurones Which may Predispose to Neurodegeneration 165 Conclusions 166 Acknowledgements 167 References 167 7 Neurodegenerative Disorders: Parkinson's Disease and Huntington's Disease 181 Parkinson's Disease 181 Huntington's Disease 190 Conclusions 194 References 195 xvi Contents 8 Molecular Pathogenesis of Neuroinflammation 201 A Brief History of Immune Privilege 201 Experimental Autoimmune Encephalomyelitis — An Animal Model to Study Interactions of the Immune System with the CNS 202 How Modern Techniques Contributed to our Understanding of Neuroinflammation in EAE and Multiple Sclerosis 204 Microdissection and Molecular Analyses of Single Cells Involved in the Disease Process 210 Novel Techniques and their Contribution to Clinical Neurology — A Future Perspective 211 Conclusion 215 Acknowledgements 215 References 215 9 Neurovirology 221 Introduction 221 Specific Techniques And Their Applications 223 Acknowledgements 236 References 236 10 Molecular Neurology of Prion Disease 241 Introduction to Prions and Historical Perspective 241 Molecular Biology of Prions 244 Application to Clinical Neurology 255 References 274 11 Monitoring and Interpretation of Intracranial Pressure 285 Methods of Measurement 287 Typical Events and Trends in ICP Monitoring 288 Waveform Analysis of ICP 292 Pressure-Volume Compensatory Reserve 293 Cerebrovascular Pressure Reactivity 294 Other Methods of ICP Analysis 296 Practical Use of the ICP Derived Parameters: "Optimal CPP" and Multiple Trend Analysis 298 Contents xvii Association with Outcome Following Severe Head Injury 299 ICP in Hydrocephalus and Benign Intracranial Hypertension 300 Attempts to Measure ICP and CPP Non-Invasively 305 Is ICP Monitoring Useful 306 Acknowledgements 308 References 308 12 Cerebral Perfusion and Stroke 315 Cerebrovascular Anatomy 316 Methods for Measurement of Cerebral Blood Flow 316 Regulation of the Normal Cerebral Circulation 319 Cerebral Circulation Responses to Focal Ischaemia 326 The Ischaemic Penumbra 327 Mechanisms of Infarction in Penumbral Tissue 333 Summary 335 References 336 13 A Review of Structural Magnetic Resonance Neuroimaging 343 Definition(s) of Structural MRI 344 Applications of Structural MRI 344 The Next Ten Years 363 Conclusion 366 Acknowledgements 366 References 367 14 Applications of Positron Emission Tomography (PET) in Neurology 377 Principles of PET 378 Application of PET to Clinical Neurology 381 Potential Future Applications 393 References 393 xviii Contents 15 Functional Magnetic Resonance Imaging 401 Principles of Functional MRI 402 Clinical Applications of fMRI 409 fMRI as a Marker of Pathological State 414 Linking fMRI to other MRI Techniques for Characterising Pathology and other Directions for the Future 415 Acknowledgements 418 References 418 16 How to Spot Bias and Other Potential Problems in Randomised Controlled Trials 423 Bias 426 Precision 431 Analysis and Inferences 434 The Future 440 Conclusions 440 Acknowledgements 441 References 441 Index 445 |
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