Neurotrauma: New Insights into Pathology and Treatment: New Insights into Pathology and Treatment
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Table of contents
- Cover
- Contentsxiii
- List of Contributorsv
- Prefacexi
- Section I: Introduction1
- Chapter 1. The impact of neurotrauma on society: an international perspective3
- Introduction3
- Neurotrauma as a global problem4
- The causes of neurotrauma4
- The community costs6
- Providing care6
- What can be done?7
- Community support for research7
- The challenge8
- The role of the INTS and neuroscience8
- References8
- Section II: Biomechanics of Injury10
- Chapter 2. CNS injury biomechanics and experimental models13
- Introduction13
- Basic biomechanics14
- Traumatic mechanical insults15
- Mechanical response to traumatic insult16
- Types of traumatic CNS injury16
- Experimental modeling of traumatic CNS injury17
- Tolerance criteria for CNS injury18
- Response phases of traumatic CNS injury19
- Future directions23
- Conclusion24
- Acknowledgements24
- References25
- Chapter 3. Linking impact to cellular and molecular sequelae of CNS injury: Modeling in vivo complex27
- Introduction27
- Biomechanical mechanisms that cause TBI in vivo28
- Reproducing injury mechanisms with in vivo TBI models29
- Broad categorization of in vivo models - what do they reproduce?29
- Mechanoactivation „ the first therapeutic target31
- Mechanoactivation cascade „ the next target33
- What therapies have emerged?34
- Pointing toward the future35
- Acknowledgments35
- References36
- Section III: Pathological Mechanisms of Injury40
- Chapter 4. Cellular and subcellular change evoked by diffuse traumatic brain injury: a complex web o43
- Introduction44
- Neuronal damage associated with DTBI44
- Axonal damage associated with DTBI49
- Concluding comments55
- Abbreviations56
- Acknowledgments56
- References56
- Chapter 5. Astroglia: Important mediators of traumatic brain injury61
- Introduction61
- Astrocytes in normal brain function: recasting an old ‘‘star’’61
- Revisiting and revising the ‘‘Classical View’’ of astrocytes in CNS trauma64
- Unraveling the mechanisms of acute astrocyte damage with in vitro mechanical injury68
- Conclusion73
- Acknowledgments73
- References73
- Chapter 6. Rescuing neurons and glia: is inhibition of apoptosis useful?81
- Introduction81
- Cell death routes82
- Apoptotic pathways83
- Crossroads of cell death84
- Inhibition of apoptosis85
- Concluding remarks90
- Abbreviations91
- Aknowledgments91
- References91
- Chapter 7. Substance P in traumatic brain injury97
- Introduction97
- Substance P99
- Neurogenic inflammation101
- NK1 receptor antagonists103
- Conclusion104
- References104
- Chapter 8. Current concepts of cerebral oxygen transport and energy metabolism after severe traumati111
- Cerebral oxygen transport111
- Cerebral energy metabolism114
- Pathophysiology118
- Abbreviations122
- References122
- Chapter 9. Progressive damage after brain and spinal cord injury: pathomechanisms and treatment stra125
- Introduction125
- Traumatic brain injury126
- Clinical evidence for progressive injury127
- Pathomechanisms underlying progressive injury128
- Spinal cord injury131
- Supraspinal alterations after SCI135
- Therapeutic interventions targeting progressive injury135
- Acknowledgments137
- References137
- Chapter 10. Injury-induced alterations in CNS electrophysiology143
- Introduction143
- In vivo models of TBI144
- Functional electrophysiological changes in the hippocampus after TBI145
- Injury-induced functional alterations in area CA1147
- Injury-induced functional alterations in the DG153
- Cellular mechanisms of abnormal electrophysiology after trauma: the effect of tensile strain on iono156
- Stretch injury alters cortical glutamate receptor function159
- Stretch injury alters cortical GABAA receptor function162
- Stretch injury alters Na+/K+ ATPase activity164
- Conclusions164
- References165
- Chapter 11. Traumatic injury of the spinal cord and nitric oxide171
- The occurrence of NADPH diaphorase-stained and/or bNOS immunoreactive neurons in the gray matter of172
- The distribution of NADPH diaphorase-positive and/or NOS immunolabeled fibers in spinal cord white m173
- NO/cGMP signaling in the spinal cord173
- NO-mediated cGMP synthesis in the spinal cord after traumatic injury174
- NOS in the spinal cord: effect of traumatic injury in the epicenter of injury175
- NADPHd-exhibiting and Fos-like immunolabeling of intrinsic spinal cord neurons in a model of MCEC177
- Immunolabeling and cNOS activity in the incipient cauda equina syndrome of the dog177
- Therapeutic interventions and NO reduction after spinal trauma178
- Abbreviations179
- Acknowledgments179
- References179
- Chapter 12. Aquaporins: role in cerebral edema and brain water balance185
- Introduction185
- Aquaporin expression in the CNS186
- Aquaporins and brain water balance186
- Cerebral edema187
- Aquaporins and cytotoxic edema188
- Aquaporins and vasogenic edema190
- Aquaporins, ICP, and traumatic brain injury191
- Conclusion192
- References193
- Chapter 13. Sodium channel expression and the molecular pathophysiology of pain after SCI195
- Introduction195
- Spinal cord sodium channels196
- SCI and dorsal horn ion channel dysregulation196
- Nav1.3 and neuronal hyperresponsiveness198
- Thalamic Nav1.3 dysregulation199
- Multi-tiered alterations in nociceptive processing200
- Conclusion201
- Acknowledgments202
- References202
- Section IV: Novel Aspects of Clinical Research in CNS Injury205
- Chapter 14. Monitoring cerebral oxygenation in traumatic brain injury207
- Introduction207
- Monitoring technologies207
- Clinical data209
- Technology comparisons211
- Summary and conclusions212
- Acknowledgments212
- References212
- Chapter 15. Update on the treatment of spinal cord injury217
- Introduction217
- Pathobiological mechanisms of SCI218
- Current non-pharmacological treatment options for SCI218
- Improving axonal conduction in the injured spinal cord220
- Neuroprotective/neuroregenerative approaches to treating the injured spinal cord221
- Cell-mediated repair of the injured spinal cord225
- Conclusion228
- References229
- Chapter 16. Cerebral contusion: a role model for lesion progression235
- Introduction235
- Histopathology of cerebral contusion235
- MR diffusion study (ADC mapping)236
- Increased cerebrovascular permeability237
- Edema fluid accumulation in the central area238
- Osmotic potential of the contusion necrosis239
- Surgical treatment239
- Results239
- Conclusion241
- References241
- Chapter 17. Ethical implications of time frames in a randomized controlled trial in acute severe tra243
- Introduction243
- Materials and methods244
- Results245
- Discussion246
- References249
- Section V: Emerging Topics in CNS Trauma251
- Chapter 18. Experimental models of repetitive brain injuries253
- Introduction253
- Experimental studies of repeated mild TBI in vivo254
- Repetitive injury and neurodegenerative disease255
- Studying repeated injuries in vitro256
- The phenomenon of preconditioning256
- Future directions257
- Abbreviations259
- Acknowledgments259
- References259
- Chapter 19. Minor traumatic brain injury in sports: a review in order to prevent neurological sequel263
- Introduction263
- Epidemiology of mTBI264
- Neuromechanics of mTBI265
- Neuropathology of mTBI270
- Neurobiology and associated neurometabolic changes of mTBI278
- Biochemical markers of mTBI282
- Conclusions285
- Acknowledgements286
- References286
- Chapter 20. Traumatic brain injury in infants: the phenomenon of subdural hemorrhage with hemispheri293
- Introduction293
- Early clinical observations293
- Experimental models296
- The role of apnea298
- The role of seizures299
- Neuropathology and clinical neurophysiology299
- Brain swelling, variability, and decompressive craniectomy299
- Pathophysiology of the ‘‘Big Black Brain’’: a hypothesis300
- Conclusion300
- References301
- Chapter 21. Traumatic brain injury and Alzheimer’s disease: a review303
- Epidemiology of TBI and AD303
- The ’Amyloid Cascade Hypothesis’304
- APP processing304
- APP and Aβ within damaged axons305
- Alzheimer’s pathology following fatal head injury in humans306
- Alzheimer’s pathology following experimental head injury307
- Epidemiological studies308
- The influence of APOE genotype on TBI outcome310
- Conclusion311
- References311
- Chapter 22. The neurotrophic protein S100B: value as a marker of brain damage and possible therapeut317
- General features and origin of the S100B protein317
- Release mechanism of S100B318
- Cellular action of S100B318
- Passage of S100B through the blood-brain barrier319
- Clinical studies319
- Effect of S100B on recovery following experimental TBI320
- Conclusion321
- References322
- Chapter 23. Cerebellar injury: clinical relevance and potential in traumatic brain injury research327
- Introduction327
- Clinical evidence of cerebellar trauma328
- Cerebellar injury in animal models329
- The cerebellum as a model of neurotrauma335
- Conclusion335
- Abbreviations335
- Acknowledgment335
- References335
- Chapter 24. Sex differences in brain damage and recovery of function: experimental and clinical find339
- Introduction339
- Traumatic brain injury is not a unitary event339
- Are there structural differences between the male and female brain that can affect plasticity and ou340
- Sex differences in the gross and cellular anatomy of the brain341
- Sex differences in the brain may be present in glial as well as neuronal morphology342
- The influence of sex differences and hormonal status on cerebral functions in normal and brain-damag344
- Sex differences in the brain-injured adult345
- Do females generally have better outcomes after brain damage than males?346
- Acknowledgment348
- References348
- Chapter 25. Heat acclimation: a unique model of physiologically mediated global preconditioning agai353
- The phenomenon of preconditioning353
- Long-term heat acclimation: physiologically mediated global preconditioning355
- HA-induced neuroprotection in closed head injury356
- Mechanisms of HA-induced neuroprotection357
- Summary359
- Abbreviations360
- References360
- Section VI: The Future of Neurotrauma: Developing Novel Treatment Strategies365
- Chapter 26. In vivo tracking of stem cells in brain and spinal cord injury367
- Introduction367
- Discussion and conclusion379
- Abbreviations381
- Acknowledgment381
- References382
- Chapter 27. Intrathecal drug delivery strategy is safe and efficacious for localized delivery to the385
- Introduction385
- Injectable delivery strategy386
- Localized release of bioactive factors386
- New fast-gelling blend shows therapeutic promise388
- Conclusions and future outlook391
- Acknowledgments391
- References391
- Chapter 28. Decompression craniectomy after traumatic brain injury: recent experimental results393
- Introduction393
- History of decompression craniectomy393
- Abbreviations398
- Acknowledgments398
- References398
- Chapter 29. Novel neuroproteomic approaches to studying traumatic brain injury401
- Introduction to TBI401
- Modeling TBI in animals403
- Neuroproteomic analysis with mass spectrometry in TBI406
- TBI neuroproteomics by antibody arrays and high-throughput blotting409
- Validation of proteomic data for TBI biomarker development411
- Translation to clinical diagnostics414
- Closing remarks415
- Disclaimer415
- References415
- Chapter 30. Remyelination of the injured spinal cord419
- Introduction419
- Remyelination in demyelinated spinal cord420
- Nodal reconstruction of remyelinated spinal cord axons422
- Transected spinal cord424
- Neuroprotection of dorsal corticospinal tract428
- OEC into spinal cord contusion injury429
- Clinical perspectives430
- Concluding remarks430
- Abbreviations430
- Acknowledgments430
- References431
- Subject Index435
Neurotrauma is the leading cause of death and disability in young adults, and the incidence in older patients is increasing. Neurotrauma is also a field in medicine with one of the highest unmet needs. Concentrated, focused and multidisciplinary efforts are required to combat this important disease. Exciting findings from basic research open opportunities for improving treatment results.
This volume presents a unique and comprehensive overview of the latest findings and insights on translational research in neurotrauma. This book should be a must for any TBI or SCI researcher interested in translating their work to the clinic, as well as to clinicians interested in the latest research findings which could provide novel treatment strategies for their patients.
• Integrates results from research on traumatic brain injury and spinal cord injury, bridging basic science and clinical research
• Includes contributions from a worldwide panel of leading researchers and clinicians in the fields of TBI and SCI
This volume presents a unique and comprehensive overview of the latest findings and insights on translational research in neurotrauma. This book should be a must for any TBI or SCI researcher interested in translating their work to the clinic, as well as to clinicians interested in the latest research findings which could provide novel treatment strategies for their patients.
• Integrates results from research on traumatic brain injury and spinal cord injury, bridging basic science and clinical research
• Includes contributions from a worldwide panel of leading researchers and clinicians in the fields of TBI and SCI