Geuna / Tos / Battiston Essays on Peripheral Nerve Repair and Regeneration

1. Auflage 2009
ISBN: 978-0-12-378574-9
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, Band Volume 87, 603 Seiten

Reihe: International Review of Neurobiology

Interest in the study of peripheral nerve repair and regeneration has increased significantly over the last twenty years and today the number of nerve reconstructions performed is progressively increasing due to the continuous improvement in surgical technology and to the spread of microsurgical skills among surgeons worldwide.  This volume of International Review of Neurobiology providdes an overview of the state of the art knowledge in peripheral nerve repair and regeneration by bringing together a number of reviews that critically address some the most important issues in this biomedical field.

Autoren/Hrsg.

Geuna, Stefano

Tos, Pierluigi

Battiston, Bruno

Inhaltsverzeichnis

1;Front Cover;1
2;International Review of Neurobiology;4
3;Copyright Page;5
4;Contents;6
5;Contributors;16
6;Preface;22
7;Chapter 1: Peripheral Nerve Repair and Regeneration Research: A Historical Note;24
7.1;I. Introduction;24
7.2;II. The 19th Century;25
7.3;III. The 20th Century;26
7.4;IV. Conclusions;27
7.5;Acknowledgments;29
7.6;References;29
8;Chapter 2: Development of the Peripheral Nerve;32
8.1;I. Introduction;33
8.2;II. Development of the Neural Components of the Peripheral Nerve;35
8.2.1;A. Developmental Properties of the Schwann Cells;35
8.2.1.1;1. The DiVerentiation of the Schwann Cell: From the Neural Crest to Mature Schwann Cell;36
8.2.1.2;2. The Interaction of the Schwann Cell and Axon in Developing PNs;37
8.2.2;B. Developmental Properties of the Axon in Peripheral Nerves;40
8.2.2.1;1. The Development of the PNs Network;40
8.2.2.2;2. The Development of the Axon Bundles;42
8.3;III. Development of the Nonneural Components of the Peripheral Nerve;42
8.3.1;A. The Embryonic Origin of Cell Types of Nerve Sheath;43
8.3.2;B. Development of the Peripheral Nerve Sheath;44
8.4;IV. Conclusion;45
8.5;Acknowledgments;46
8.6;References;46
9;Chapter 3: Histology of the Peripheral Nerve and Changes Occurring During Nerve Regeneration;50
9.1;I. Introduction;51
9.2;II. Structure and Ultrastructure of the Peripheral Nerve;52
9.2.1;A. The ``Parenchyma´´ of the Nerve;53
9.2.1.1;1. Myelinated Nerve Fibers;53
9.2.1.2;2. Unmyelinated Nerve Fibers;55
9.2.2;B. The ``Stroma´´ of the Nerve: Nerve Fibers;56
9.3;III. Morphological Changes after Nerve Damage and Regeneration;58
9.3.1;A. The Proximal Nerve Segment;59
9.3.1.1;1. Perikaryal Phenotype Following Nerve Damage and Regeneration;60
9.3.2;B. The Distal Nerve Segment;61
9.4;IV. Conclusions;63
9.5;Acknowledgments;64
9.6;References;64
10;Chapter 4: Methods and Protocols in Peripheral Nerve Regeneration Experimental Research: Part I-Experimental Models;70
10.1;I. Introduction;71
10.2;II. In Vitro Models of Axonal Elongation;71
10.2.1;A. Immortalized Neuronal and Glial Cell Lines;72
10.2.2;B. Primary Neuronal and Glial Cultures;72
10.2.3;C. 3D and Organotypic Cocultures;73
10.3;III. In Vivo Animal Models for the Study of Nerve Repair and Regeneration;74
10.4;IV. Experimental Lesion Paradigms for Nerve Regeneration Research;75
10.4.1;A. Axonotmesis;82
10.4.2;B. Neurotmesis;84
10.5;V. Selection of the Nerve Model;85
10.5.1;A. Hindlimb Nerves;86
10.5.2;B. Forelimb Nerves;86
10.5.2.1;1. Functional Anatomy of Finger Movements;87
10.5.2.2;2. The Grasping Test;88
10.5.2.3;3. The Ulnar Test;90
10.5.2.4;4. Functional Assessment of the Radial Nerve by Means of the Grasping Test;91
10.5.3;C. Other Nerve Models;93
10.6;VI. Interfering Conditions and Disease Models;93
10.7;VII. Conclusions;94
10.8;Acknowledgments;96
10.9;References;96
11;Chapter 5: Methods and Protocols in Peripheral Nerve Regeneration Experimental Research: Part II-Morphological Techniques;104
11.1;I. Introduction;105
11.2;II. Light Microscopy;105
11.2.1;A. Fixation Procedures;105
11.2.2;B. Embedding Procedures;105
11.2.2.1;1. Paraffin Embedding Protocol;106
11.2.2.2;2. Cryo-embedding Protocol;106
11.2.3;C. Staining Procedures;106
11.2.3.1;1. Hematoxylin and Eosin Staining;106
11.2.3.2;2. Masson’s Trichrome Staining;108
11.2.3.3;3. Pre-embedding Myelin Sheath Stain with Osmium Tetroxidebefore Paraffin Embedding;108
11.2.3.4;4. Toluidine Blue Staining of Semithin Sections from Resin-embedded Blocks;109
11.2.3.5;5. Polychrome Staining of Semithin Sections from Resin-embedded Blocks;109
11.3;III. Immunohistochemistry and Confocal Microscopy;109
11.3.1;A. Fixation Procedures;109
11.3.2;B. Embedding Procedures;109
11.3.2.1;1. ‘‘Etching’’ Procedure for Immunohistochemistry after Pre-embeddingOsmium Tetroxide Staining;110
11.3.3;C. Antibodies and Immunostaining Procedures;110
11.3.3.1;1. Immunofluorescence;113
11.3.3.2;2. Immunoperoxidase;113
11.4;IV. Electron Microscopy;113
11.4.1;A. Fixation Procedures;113
11.4.2;B. Embedding Procedures;114
11.4.3;C. Cutting and Staining Procedures;114
11.5;V. Histomorphometry (Stereology);116
11.5.1;A. Comparison of Quantitative Estimates Between Resin- and Paraffi;n-Embedded Nerve Specimens;121
11.6;VI. Conclusions;122
11.7;Acknowledgments;124
11.8;References;124
12;Chapter 6: Methods and Protocols in Peripheral Nerve Regeneration Experimental Research: Part III-Electrophysiological Evaluation;128
12.1;I. Introduction;129
12.2;II. Nerve Conduction Tests: Technical Bases;130
12.3;III. Electrophysiological Evaluation of Axonal Regeneration;132
12.4;IV. Electrophysiological Evaluation of Regeneration and Reinnervation;134
12.4.1;A. Nerve Conduction Tests;134
12.4.2;B. Motor Nerve Conduction Tests;135
12.4.3;C. Usefulness of Nerve Conduction Tests for Assessment of Nerve Regeneration;138
12.5;V. Electrophysiological Evaluation of Spinal Reflexes and Central Connectivity;141
12.5.1;A. Spinal Reflexes;141
12.5.2;B. Sensory and Motor Evoked Responses;142
12.6;VI. EMG: Evaluation of Muscle Reinnervation;143
12.7;VII. Electrophysiological Characterization of Electrical Properties of Regenerated Nerves;145
12.8;Acknowledgments;145
12.9;References;146
13;Chapter 7: Methods and Protocols in Peripheral Nerve Regeneration Experimental Research: Part IV-Kinematic Gait Analysis to Quantify Peripheral Nerve Regeneration in the Rat;150
13.1;I. Introduction;151
13.2;II. Walking Track Analysis;152
13.2.1;A. Walking Tracks;152
13.2.2;B. Analysis of Walking Tracks;152
13.2.3;C. Limitations of the SFI;153
13.3;III. Computerized Gait Analysis;154
13.3.1;A. Calculation of SFI;155
13.3.2;B. Gait-Stance Duration;155
13.3.3;C. Ankle Kinematics;156
13.3.4;D. Toe out Angle;158
13.4;IV. Gait Analysis in the Forelimb Nerve Injury Models;158
13.5;V. Conclusions and Future Perspectives;159
13.6;Acknowledgment;159
13.7;References;159
14;Chapter 8: Current Techniques and Concepts in Peripheral Nerve Repair;164
14.1;I. Introduction;165
14.2;II. Timing of Nerve Repair;167
14.3;III. Direct Repair;168
14.3.1;A. End-To-End Repair;168
14.3.2;B. Epineural Sleeve Repair;171
14.3.3;C. End-To-Side Repair;172
14.4;IV. Nerve Grafting;173
14.4.1;A. Nerve Autografts;174
14.4.2;B. Nerve Allografts;177
14.4.2.1;1. MHC Matching;178
14.4.2.2;2. Graft Pretreatment;178
14.4.2.3;3. Immunosuppression;179
14.4.2.4;4. Tolerance Induction;179
14.5;V. Conduit Repair;181
14.5.1;A. Biological Conduits;181
14.5.2;B. Artificial Conduits;183
14.6;VI. Conclusions;186
14.7;References;187
15;Chapter 9: Artificial Scaffolds for Peripheral Nerve Reconstruction;196
15.1;I. Introduction;197
15.2;II. Materials for Peripheral Nerve Repair;199
15.2.1;A. Nondegradable Materials for Nerve Guides;199
15.2.2;B. Biodegradable Synthetic Materials for Nerve Guides;200
15.2.3;C. Natural Polymers for Nerve Guides;202
15.3;III. Techniques for the Production of Scaffolds for Peripheral Nerve Repair from Synthetic Polymers;206
15.4;IV. Functionalized Bioactive Materials for Axon Regeneration;209
15.4.1;A. Haptotactic Cues;210
15.4.2;B. Chemotactic Cues;211
15.5;V. Conclusion;213
15.6;References;214
16;Chapter 10: Conduit Luminal Additives for Peripheral Nerve Repair;222
16.1;I. Introduction;223
16.2;II. Cellular Components;223
16.2.1;A. Schwann Cells;224
16.2.2;B. Bone Stromal Cells;225
16.2.3;C. Fibroblasts;226
16.2.4;D. Other Cellular Components;226
16.3;III. Structural Components;227
16.3.1;A. Fibrin;227
16.3.2;B. Laminin;228
16.3.3;C. Collagen;229
16.3.4;D. Synthetic Longitudinal Matrices;231
16.4;IV. Neurotrophic Components;231
16.4.1;A. Fibroblast Growth Factor (FGF);231
16.4.2;B. Nerve Growth Factor (NGF);232
16.4.3;C. Glial Growth Factor (GGF);233
16.4.4;D. Ciliary Neurotrophic Factor (CNTF);233
16.5;V. VEGF;233
16.6;VI. GDNF;233
16.6.1;A. Other Factors;234
16.7;VII. Combined Additives;234
16.8;VIII. Recommendations;235
16.9;IX. Conclusion;241
16.10;References;242
17;Chapter 11: Tissue Engineering of Peripheral Nerves;250
17.1;I. Introduction;251
17.2;II. Microsurgery;252
17.3;III. Cell and Tissue Transplantation;253
17.3.1;A. A Combined Tissue Autotransplantation Approach: The Muscle-Vein-Combined Technique;254
17.4;IV. Material Science-Biomaterials for Nerve Reconstruction;258
17.5;V. Gene Transfer;260
17.6;VI. Clinical Experience;261
17.6.1;A. Polymeric Scaffolds;261
17.6.2;B. Biomimetic and Biological Scaffolds;262
17.6.3;C. Muscle-Vein-Combined Scaffolds;263
17.7;VII. Conclusions;264
17.8;Acknowledgments;265
17.9;References;265
18;Chapter 12: Mechanisms Underlying The End-to-Side Nerve Regeneration;274
18.1;I. Introduction;275
18.2;II. Proposed Mechanisms and Experimental Techniques;275
18.3;III. Proximal Stump Contamination;277
18.4;IV. Collateral Sprouting;277
18.5;V. Terminal/Regenerating Sprouting;281
18.6;VI. Stimuli Needed for Triggering Nerve Sprouting;284
18.7;VII. Pruning;285
18.8;VIII. Brain Plasticity;286
18.9;Acknowledgments;287
18.10;References;287
19;Chapter 13: Experimental Results in End-To-Side Neurorrhaphy;292
19.1;I. Introduction;292
19.2;II. Source of Regenerating Axons;293
19.3;III. Molecular Mechanism of Collateral Sprouting;294
19.4;IV. Degree of Motor Versus Sensory Regeneration;296
19.5;V. Results in Various End-to-Side Surgical Models;297
19.6;VI. Conclusions;299
19.7;References;300
20;Chapter 14: End-to-Side Nerve Regeneration: From the Laboratory Bench to Clinical Applications;304
20.1;I. Introduction;305
20.2;II. Basic Science Studies;306
20.3;III. Clinical Studies;308
20.3.1;A. Sensory Nerves;309
20.3.2;B. Mixed Nerves and Brachial Plexus;310
20.4;IV. Future Perspectives;311
20.5;Acknowledgments;312
20.6;References;312
21;Chapter 15: Novel Pharmacological Approaches to Schwann Cells as Neuroprotective Agents for Peripheral Nerve Regeneration;318
21.1;I. Introduction;319
21.2;II. GABAergic System;320
21.3;III. Neuroactive Steroids;322
21.4;IV. Glutamate;325
21.5;V. Cholinergic System;326
21.6;VI. Purinergic System;328
21.7;VII. Mitogen-Activated Protein Kinases (MAPKs);330
21.8;VIII. Other Approaches;331
21.9;IX. Conclusions;332
21.10;Acknowledgment;333
21.11;References;333
22;Chapter 16: Melatonin and Nerve Regeneration;340
22.1;I. Introduction;341
22.2;II. The Effects of Melatonin on Peripheral Nerves;344
22.2.1;A. The Effects of Melatonin on Ischemia-Reperfusion Injury in the Peripheral Nerves;344
22.2.2;B. The Effects of Melatonin on Painful Situations During Peripheral Nerve Injury;345
22.2.3;C. The Effects of Melatonin After Peripheral Nerve Transection and PNI;346
22.2.4;D. Optic Nerve Studies with Melatonin;350
22.3;III. Melatonin Toxicity on Peripheral Nerves;351
22.4;IV. Conclusion;352
22.5;References;353
23;Chapter 17: Transthyretin: An Enhancer of Nerve Regeneration;360
23.1;I. Introduction;360
23.2;II. Transthyretin;361
23.3;III. TTR KO Mice;362
23.4;IV. TTR Mutations as the Cause of FAP;362
23.5;V. TTR Enhances Nerve Regeneration;363
23.5.1;A. Lack of TTR Leads to Delayed Nerve Regeneration;364
23.5.2;B. Cellular Mechanism Underlying the Effect of TTR on Nerve Regeneration;365
23.6;VI. Conclusion;367
23.7;Acknowledgments;367
23.8;References;367
24;Chapter 18: Enhancement of Nerve Regeneration and Recovery by Immunosuppressive Agents;370
24.1;I. Introduction;371
24.1.1;A. Immunophilins;372
24.2;II. Promoting Axon Regeneration;373
24.2.1;A. Central Nervous System;373
24.2.2;B. Peripheral Nervous System;374
24.3;III. Neuroprotection;375
24.3.1;A. Calcium Stabilization;376
24.3.2;B. Hypothermia;376
24.4;IV. Timing of Administration of FK506;376
24.5;V. Concentration of Neurotrophic Activity;377
24.6;VI. Mechanisms of Action of FK506;377
24.7;VII. Side Effects of FK506;378
24.8;VIII. Clinical Applications;379
24.9;IX. Conclusion;379
24.10;References;380
25;Chapter 19: The Role of Collagen in Peripheral Nerve Repair;386
25.1;I. Introduction;387
25.1.1;A. Outline of the Review;387
25.1.2;B. Peripheral Nerve Repair: An Historical Overview;387
25.2;II. Peripheral Nerve Collagens: Structure, Synthesis and Function;388
25.2.1;A. Collagen Structure and Types;389
25.2.2;B. Collagen Biosynthesis;391
25.2.3;C. Collagen Function in Peripheral Nerve Development and Repair;393
25.3;III. Excessive Collagen Formation can Act as Mechanical Barrier After PNI;395
25.4;IV. Inhibition of Collagen Synthesis Affects Peripheral Nerve Regeneration;396
25.5;References;398
26;Chapter 20: Gene Therapy Perspectives for Nerve Repair;404
26.1;I. Introduction;404
26.2;II. Gene Transfer Technologies to Target the Peripheral Nervous System;405
26.2.1;A. Where We Stand Now;405
26.2.2;B. Design and Optimization of Novel Vectors to Target the Peripheral Nervous System;407
26.2.2.1;1. Design of Expression Cassettes with Optimized Promoter Choice and Regulatory Elements;407
26.2.2.2;2. Problems and Promises in the Use of Herpes Simplex Virus Vectors;408
26.2.2.3;3. Novel Lentiviral Vectors;408
26.3;III. Emerging Concepts in Gene Therapy for Nerve Repair;409
26.3.1;A. Neurovascular Cross-Talk in the PNS;409
26.3.2;B. AAV-Transduced Muscle Scaffolds;410
26.3.3;C. Scwhann Cells: An Overlooked Target in the PNS;411
26.4;IV. Conclusions;412
26.5;References;412
27;Chapter 21: Use of Stem Cells for Improving Nerve Regeneration;416
27.1;I. Nerve Repair and Regeneration;416
27.2;II. Schwann Cells for Nerve Regeneration;417
27.3;III. Stem Cells for Regenerative Medicine;419
27.4;IV. Stem Cells for Nerve Regeneration;420
27.5;V. Conclusions;421
27.6;References;422
28;Chapter 22: Transplantation of Olfactory Ensheathing Cells for Peripheral Nerve Regeneration;428
28.1;I. Consequences of Nerve Injury;429
28.2;II. Unique Properties of Olfactory Ensheathing Cells;430
28.3;III. OECs in Spinal Cord Injury;431
28.4;IV. OECs in Peripheral Nerve Repair and Contribution of OEC Transplantation to Peripheral Nerve Repair;431
28.5;V. Challenges in Cell-Therapy Approaches for Peripheral Nerve Repair;433
28.6;VI. Prospects of Cell-Based Clinical Approaches;434
28.7;References;436
29;Chapter 23: Manual Stimulation of Target Muscles has Different Impact on Functional Recovery after Injury of Pure Motor or Mixed Nerves;440
29.1;I. Introduction;441
29.2;II. Manual Stimulation;443
29.2.1;A. Effects of MS on Functional Recovery After Facial Nerve Injury;443
29.2.2;B. Effects of MS on Functional Recovery After Hypoglossal Nerve Injury;445
29.2.3;C. Effects of MS on Functional Recovery After Injury of a Mixed Peripheral Nerve;448
29.3;III. Discussion;448
29.4;References;452
30;Chapter 24: Electrical Stimulation for Improving Nerve Regeneration: Where do we Stand?;456
30.1;I. Introduction;457
30.2;II. Basis for Poor Functional Recovery After Nerve Injury and Repair;457
30.3;III. The Potential of Brief Electrical Stimulation for Accelerating Axon Regeneration;458
30.3.1;A. Wallerian Degeneration and Staggered Axon Regeneration into the Distal Nerve Stump;458
30.3.2;B. Electrical Stimulation Accelerates Axon Outgrowth in Nerve Injury;461
30.4;IV. Conclusions;464
30.5;Acknowledgments;465
30.6;References;465
31;Chapter 25: Phototherapy in Peripheral Nerve Injury: Effects on Muscle Preservation and Nerve Regeneration;468
31.1;I. Introduction;469
31.2;II. Phototherapy in Denervated Muscle Preservation;471
31.2.1;A. Creatine Kinase (CK) Activity in Intact and Denervated Rat Gastrocnemius Muscle;472
31.2.2;B. Acetylcholine Receptors Synthesis in Intact and Denervated Rat Gastrocnemius Muscle;472
31.2.3;C. Is Laser Phototherapy Damaging to the Muscle?;473
31.2.4;D. Can Laser Phototherapy Prevent Denervation Muscle Atrophy?;474
31.3;III. Phototherapy in Peripheral Nerve Regeneration;475
31.3.1;A. Incomplete Peripheral Nerve Injury;475
31.3.1.1;1. Experimental Peripheral Nerve Crush Injury;475
31.3.2;B. Complete Peripheral Nerve Injury;476
31.3.2.1;1. Regeneration of the Transected Sciatic Nerve in Rat After Primary Anastomosis;476
31.3.2.2;2. Median Nerve Regeneration in the Rat After End-to-Side Anastomosis;477
31.3.2.3;3. Regeneration of the Sciatic Nerve in the Rat After Complete Segmental Loss andNeurotube Reconstruction;477
31.4;IV. Phototherapy on Nerve Cell Growth In Vitro as a Potential Procedure for Cell Therapy;480
31.5;V. 780-nm Laser Phototherapy in Clinical Trial;481
31.5.1;A. Laser Dosage;482
31.6;VI. Conclusions;484
31.7;References;485
32;Chapter 26: Age-Related Differences in the Reinnervation after Peripheral Nerve Injury;488
32.1;I. Introduction;489
32.2;II. Age-Related Changes in the PNS;489
32.3;III. Ageing and Reinnervation After Peripheral Nerve Injury;491
32.3.1;A. Aging and Axon Regeneration After Peripheral Nerve Injury;491
32.3.2;B. Ageing and Collateral Sprouting of Uninjured Axons;492
32.3.3;C. Are All Subpopulations of Peripheral Neurons Equally Affected by Aging?;494
32.4;IV. Possible Reasons for Impaired Reinnervation with Aging;494
32.4.1;A. Survival of Aged Noninjured and Injured Neurons;495
32.4.2;B. Regenerating and Sprouting Capacity of Aged Neurons;495
32.4.3;C. Responsiveness of Aged Regenerating and Sprouting Axons to the Pathway- or Target-Derived Neurotrophic Factors;496
32.4.4;D. Alterations in the Aged Peripheral Neural Pathways and Target Tissues;498
32.5;V. Conclusions;500
32.6;References;500
33;Chapter 27: Neural Plasticity After Nerve Injury and Regeneration;506
33.1;I. Introduction;507
33.2;II. Neuronal Survival and Reaction to Axotomy;508
33.2.1;A. Changes in Ion Channels and Excitability in Injured Neurons;511
33.2.2;B. Synaptic Plasticity of Axotomized Neurons;512
33.3;III. Plastic Changes and Remodeling at the Spinal Cord;513
33.3.1;A. Changes in Spinal Reflexes After Nerve Lesions;513
33.3.2;B. Remodeling of Spinal Cord Projections and Circuits;514
33.4;IV. Plastic Changes and Reorganization at Cortical and Subcortical Levels;515
33.4.1;A. Reorganization at Subcortical Levels;516
33.4.2;B. Reorganization of Somatosensory Cortex;516
33.4.3;C. Reorganization of Motor Cortex;518
33.4.4;D. Mechanisms of Cortical and Subcortical Plasticity;519
33.5;V. Remodeling CNS Plasticity;520
33.6;Acknowledgments;521
33.7;References;521
34;Chapter 28: Future Perspective in Peripheral Nerve Reconstruction;530
34.1;I. Introduction;531
34.2;II. Intracellular Signaling;531
34.3;III. Development of Nerve Repair and Reconstruction;532
34.4;IV. Nerve Reconstruction: Technique and Alternatives;533
34.5;V. Signal Transduction in Peripheral Nerve Regeneration;534
34.5.1;A. The Injury Signal and the Cell Body Reaction;534
34.5.2;B. Extrinsic Properties Required for Axon Growth and Target Finding;537
34.6;VI. Nanotechnology and Nerve Regeneration;537
34.6.1;A. Nanostructures for Neurite Regeneration;539
34.6.2;B. Neurites and Topography: From Micro to Nano;539
34.6.3;C. Why Nanostructures?;541
34.6.4;D. From Cell Reactions to Nanostructures In Vitro to Nerve Regeneration Applications;544
34.7;VII. Clinical Development: Future Perspectives;545
34.8;Acknowledgments;547
34.9;References;547
35;Index;554
36;Contents of Recent Volumes;566
37;Color Plates;596