Every year, an estimated 1.7 million Americans sustain brain injury. Long-term disabilities impact nearly half of moderate brain injury survivors, and nearly 50,000 of these cases result in death, with an approximate $76.5 billion being spent on direct and indirect medical costs.

Over the last decade, the field of neurotrauma has witnessed significant advances, especially at the molecular, cellular, and behavioral levels. This progress is largely due to the introduction of novel techniques, as well as the development of new animal models of central nervous system (CNS) injury.

Written by more than one hundred globally renowned experts in the field of CNS injury, Brain Neurotrauma: Molecular, Neuropsychological, and Rehabilitation Aspects provides a comprehensive and up-to-date account of the latest developments in the area of neurotrauma, including biomarker development, experimental models, diagnostic methods, and therapeutic interventions in brain injury research.

Contents

• Dedication
• Series Preface
• Foreword
• Preface
• Acknowledgments
• Editors
• Contributors
• 1. Experimental CNS Trauma: A General Overview of Neurotrauma Research
  Jonathan Lifshitz.
  • 1.1. CLINICAL SIGNIFICANCE OF NEUROTRAUMA RESEARCH: WHAT DOES TRANSLATIONAL MEAN?
  • 1.2. THE TIME FRAME FOR TBI
  • 1.3. BEHAVIORAL DEFICITS AND ENDURING MORBIDITY DEFINE TBI PHASES
  • 1.4. MILD AND DIFFUSE TBIS ARE DIFFICULT TO DIAGNOSE AND TREAT
  • 1.5. TBI INCLUDES THE NEUROVASCULAR UNIT, NOT JUST THE NEURONS
  • 1.6. CIRCUITS ARE THE PRINCIPAL CASUALTY OF TBI
  • REFERENCES
• 2. Combat TBI: History, Epidemiology, and Injury Modes
  Ralph G DePalma.
  • 2.1. INTRODUCTION
  • 2.2. HISTORY
  • 2.3. EPIDEMIOLOGY
  • 2.4. INJURY MODES: FOCUS ON BLAST EFFECTS
  • ACKNOWLEDGMENTS
  • REFERENCES
• I. Neuromechanisms in Brain Injury
  • 3. Development of Concepts in the Pathology of Traumatic Axonal and Traumatic Brain Injury
    William L Maxwell.
    • 3.1. INTRODUCTION
    • 3.2. TBI: SIMPLE OR COMPLEX?
    • 3.3. HISTOPATHOLOGY AND RESOLUTION OF MODES OF AXONAL DEGENERATION
    • 3.4. TRANSMISSION ELECTRON MICROSCOPY (TEM)
    • 3.5. INJURY OF AXONAL MITOCHONDRIA
    • 3.6. RESPONSES BY COMPONENTS OF THE AXONAL CYTOSKELETON
    • 3.7. SECONDARY AXOTOMY AND “DIEBACK”
    • REFERENCES
  • 4. Pathophysiology of Mild TBI: Implications for Altered Signaling Pathways
    Robert A Laskowski, Jennifer A Creed, and Ramesh Raghupathi.
    • 4.1. INTRODUCTION
    • 4.2. EXPERIMENTAL APPROACHES TO STUDYING CONCUSSIONS
    • 4.3. AXONAL INJURY AFTER MILD TBI
    • 4.4. WORKING MEMORY DEFICITS AND DOPAMINERGIC SIGNALING IN MILD TBI
    • 4.5. CONCLUSION
    • ACKNOWLEDGMENT
    • REFERENCES
  • 5. Oxidative Stress, Brain Edema, Blood–Brain Barrier Permeability, and Autonomic Dysfunction from Traumatic Brain Injury
    Hale Zerrin Toklu and Nihal Tümer.
    • 5.1. INTRODUCTION
    • 5.2. TRAUMATIC BRAIN INJURY
    • 5.3. ROLE OF OXIDATIVE STRESS IN TBI
    • 5.4. BRAIN EDEMA AFTER TBI
    • 5.5. BLOOD BRAIN BARRIER PERMEABILITY AFTER TBI
    • 5.6. TRAUMATIC BRAIN INJURY AND AUTONOMIC DYSFUNCTION
    • 5.7. TRAUMATIC BRAIN INJURY AND CEREBROVASCULAR FUNCTION
    • 5.8. CONCLUSION
    • REFERENCES
  • 6. The Contributing Role of Lipid Peroxidation and Protein Oxidation in the Course of CNS Injury Neurodegeneration and Neuroprotection: An Overview
    Edward D Hall.
    • 6.1. INTRODUCTION
    • 6.2. LIPID PEROXIDATION
    • 6.3. PROTEIN CARBONYLATION AND NITRATION
    • 6.4. INTERACTION OF OXIDATIVE DAMAGE WITH OTHER SECONDARY INJURY MECHANISMS
    • 6.5. MECHANISMS FOR PHARMACOLOGICAL INHIBITION OF OXIDATIVE DAMAGE IN TBI
    • 6.6. NEUROPROTECTIVE EFFECTS OF PHARMACOLOGICAL ANTIOXIDANTS
    • 6.7. RATIONALE FOR COMBINATION ANTIOXIDANT TREATMENT OF TBI
    • ACKNOWLEDGMENTS
    • REFERENCES
  • 7. IGF-1/IGF-R Signaling in Traumatic Brain Injury: Impact on Cell Survival, Neurogenesis, and Behavioral Outcome
    Sindhu K Madathil and Kathryn E Saatman.
    • 7.1. INTRODUCTION
    • 7.2. IGF-1 SIGNALING AFTER TBI
    • 7.3. PHYSIOLOGICAL ROLES OF IGF-1 WITH IMPLICATIONS FOR TBI
    • 7.4. THERAPEUTIC POTENTIAL OF IGF-1
    • 7.5. CONCLUSION
    • ACKNOWLEDGMENT
    • REFERENCES
  • 8. Microglia in Experimental Brain Injury: Implications on Neuronal Injury and Circuit Remodeling
    Megan N Evilsizor, Helen F Ray-Jones, Timothy W Ellis, Jr, Jonathan Lifshitz, and Jenna M Ziebell.
    • 8.1. INTRODUCTION
    • 8.2. INFLAMMATION IN THE CNS
    • 8.3. MICROGLIAL ACTIVITY AFTER TBI
    • 8.4. ANTI-INFLAMMATORY TREATMENTS TO REDUCE MICROGLIAL ACTIVATION
    • 8.5. CONCLUSION
    • REFERENCES
  • 9. Evaluating the Effects of APOE4 after Mild Traumatic Brain Injury in Experimental Models
    Rebekah Mannix and William P Meehan, III.
    • 9.1. INTRODUCTION
    • 9.2. TRANSGENIC MODELS OF APOE
    • 9.3. MILD TBI MODELS USING TRANSGENIC MODELS OF APOE
    • 9.4. CONCLUSION AND PERSPECTIVES
    • REFERENCES
  • 10. Cytoprotective Role of Prostaglandin D₂ DP1 Receptor against Neuronal Injury Following Acute Excitotoxicity and Cerebral Ischemia
    Sylvain Doré and Abdullah Shafique Ahmad.
    • 10.1. INTRODUCTION
    • 10.2. STROKE PATHOPHYSIOLOGY
    • 10.3. HYPOXIA, FREE RADICAL DAMAGE, ENERGY DEPLETION, AND NEURONAL DEPOLARIZATION
    • 10.4. EXCITOTOXICITY, CALCIUM SIGNALING, AND ACTIVATION OF PROSTANOID SYNTHESIS
    • 10.5. TREATMENTS AVAILABLE FOR STROKE
    • 10.6. AA CASCADE
    • 10.7. COX AND NEURODEGENERATION
    • 10.8. PG SYNTHESES
    • 10.9. PGs AND THEIR HIGH-AFFINITY RECEPTORS
    • 10.10. PGD₂ AND ITS METABOLISM
    • 10.11. PGD₂ AND DP RECEPTORS
    • 10.12. DP1 RECEPTOR
    • 10.13. THE ROLE OF PGD₂ AND DP1 RECEPTOR IN STROKE
    • 10.14. CONCLUSION
    • ACKNOWLEDGMENTS
    • REFERENCES
• II. Management in CNS Trauma
  • 11. Chronic Pain in Neurotrauma: Implications on Spinal Cord and Traumatic Brain Injury
    Rabih A Moshourab, Michael Schäfer, and Elie D Al-Chaer.
    • 11.1. INTRODUCTION
    • 11.2. PAIN SYNDROMES AFTER NEUROTRAUMA
    • 11.3. ANIMAL MODELS OF PAIN AFTER NEUROTRAUMA
    • 11.4. MECHANISMS
    • REFERENCES
  • 12. Nonconvulsive Seizures as Secondary Insults in Experimental Traumatic Brain Injury
    Laura Stone McGuire, Amade Bregy, Justin Sick, W. Dalton Dietrich, Helen M Bramlett, and Thomas Sick.
    • 12.1. INTRODUCTION
    • 12.2. CLINICAL EVIDENCE
    • 12.3. EXPERIMENTAL EVIDENCE
    • 12.4. EEG
    • 12.5. CONCLUSION
    • ACKNOWLEDGMENTS
    • REFERENCES
  • 13. Characterization and Management of Headache after Mild Traumatic Brain Injury
    Sylvia Lucas.
    • 13.1. INTRODUCTION
    • 13.2. POSTTRAUMATIC HEADACHE AND POSTCONCUSSIVE SYMPTOMS
    • 13.3. SPECIAL POPULATIONS
    • 13.4. MANAGEMENT OF PTH
    • 13.5. ACUTE PTH TREATMENT
    • 13.6. PREVENTIVE PTH TREATMENT
    • 13.7. CONCLUSION
    • REFERENCES
  • 14. Traumatic Brain Injury (TBI)-Induced Spasticity: Neurobiology, Treatment, and Rehabilitation
    Prodip Bose, Jiamei Hou, and Floyd J Thompson.
    • 14.1. INTRODUCTION
    • 14.2. MEASUREMENT OF SPASTICITY
    • 14.3. PATHOPHYSIOLOGY OF SPASTICITY
    • 14.4. TREATMENT AND REHABILITATION OF TBI-INDUCED SPASTICITY
    • 14.5. REHABILITATION OF TBI-INDUCED SPASTICITY AND LONG-TERM BENEFICIAL OUTCOME
    • REFERENCES
• III. Modeling Brain Injury
  • 15. Techniques and Methods of Animal Brain Surgery: Perfusion, Brain Removal, and Histological Techniques
    Jihane Soueid, Amaly Nokkari, and Joelle Makoukji.
    • 15.1. INTRODUCTION
    • 15.2. MATERIALS
    • 15.3. METHODS
    • 15.4. CONCLUSION
    • REFERENCES
  • 16. Controlled Cortical Impact Model
    Nicole D Osier, Jonathan R Korpon, and C. Edward Dixon.
    • 16.1. INTRODUCTION: DEVELOPMENT AND KEY FEATURES OF CCI
    • 16.2. CCI DEVICES
    • 16.3. CLINICAL RELEVANCE
    • 16.4. APPLICATIONS OF CCI TO VARIOUS LABORATORY ANIMAL SPECIES
    • 16.5. CONSIDERATIONS FOR RESEARCHERS
    • 16.6. STANDARD RAT PROTOCOL USING PNEUMATIC CCI
    • 16.7. CONCLUSION
    • ACKNOWLEDGMENTS
    • REFERENCES
  • 17. A Two-Model Approach to Investigate the Mechanisms Underlying Blast-Induced Traumatic Brain Injury
    Haoxing Chen, Shlomi Constantini, and Yun Chen.
    • 17.1. INTRODUCTION
    • 17.2. THE “IRON LUNG”–LIKE PROTECTIVE DEVICES USED TO INVESTIGATE THE MECHANISMS OF BLAST-INDUCED TBI
    • 17.3. THE ANIMAL MODEL FOR STUDYING TBI INDUCED BY SHOCK WAVES GENERATED FROM SHOCK TUBES
    • 17.4. ANIMAL MODEL FOR STUDYING TBI CAUSED BY DETONATION OF SMALL EXPLOSIVE C4 CHARGES IN A FREE FIELD
    • 17.5. COMPARATIVE STUDY BETWEEN TWO ANIMAL MODELS
    • 17.6. CONCLUSIONS
    • REFERENCES
  • 18. Acute Pathophysiology of Blast Injury—From Biomechanics to Experiments and Computations: Implications on Head and Polytrauma
    Namas Chandra and Aravind Sundaramurthy.
    • 18.1. INTRODUCTION
    • 18.2. PMHS BLAST TESTING
    • 18.3. ANIMAL MODEL BLAST TESTING
    • 18.4. COMPUTER MODELS
    • 18.5. MECHANICS OF BLAST WAVE–HUMAN HEAD INTERACTIONS WITH HELMETS
    • 18.6. CONCLUSION
    • ACKNOWLEDGEMENTS
    • REFERENCES
  • 19. Modeling Fluid Percussion Injury: Relevance to Human Traumatic Brain Injury
    Katharine Eakin, Rachel K Rowe, and Jonathan Lifshitz.
    • 19.1. INTRODUCTION
    • 19.2. MATERIALS
    • 19.3. PROCEDURE
    • 19.4. INJURY OUTCOME ASSESSMENT TECHNIQUES
    • 19.5. TROUBLESHOOTING
    • 19.6. VARIATIONS
    • REFERENCES
• IV. Imaging and Biomarkers
  • 20. CNS Trauma Biomarkers and Surrogate Endpoints Pipeline from Bench to Bedside: A Translational Perspective
    Tarek H Mouhieddine, Leeanna El Houjeiri, Mirna Sabra, Ronald L Hayes, and Stefania Mondello.
    • 20.1. INTRODUCTION
    • 20.2. BIOMARKERS VERSUS CLINICAL ENDPOINTS
    • 20.3. SURROGATE ENDPOINT
    • 20.4. VALIDITY OF A BIOMARKER AS A SURROGATE ENDPOINT
    • 20.5. ADVANTAGES AND CAPABILITIES OF BIOMARKERS AS SURROGATE ENDPOINTS
    • 20.6. DRAWBACKS AND RISKS OF BIOMARKER USE
    • 20.7. BIOMARKERS OF TRAUMATIC BRAIN INJURY
    • 20.8. LIMITATIONS AND CHALLENGES
    • 20.9. STRATEGY FOR REGULATORY APPROVAL BY FDA
    • 20.10. CONCLUSION
    • REFERENCES
  • 21. The Use and Potential of pNF-H as a General Blood Biomarker of Axonal Loss: An Immediate Application for CNS Injury
    Gerry Shaw.
    • 21.1. INTRODUCTION
    • 21.2. WHAT IS A GOOD BIOMARKER?
    • 21.3. CHARACTERISTICS OF GOOD POTENTIAL BIOMARKERS
    • 21.4. PROBLEMS WITH BIOMARKER ASSAYS
    • 21.5. OTHER NEUROFILAMENT SUBUNITS
    • 21.6. QUESTIONS ABOUT BIOMARKER ASSAYS
    • 21.7. CONFOUNDING FACTORS
    • 21.8. ENDOGENOUS LEVELS OF BIOMARKER PROTEINS
    • 21.9. CONCLUSION
    • REFERENCES
  • 22. Exploring Serum Biomarkers for Mild Traumatic Brain Injury
    Linda Papa, Damyan Edwards, and Michelle Ramia.
    • 22.1. INTRODUCTION
    • 22.2. BIOFLUID BIOMARKERS OF ASTROGLIAL INJURY
    • 22.3. BIOFLUID BIOMARKERS OF NEURONAL INJURY
    • 22.4. Biofluid biomarkers of axonal injury
    • 22.5. CONCLUSION
    • REFERENCES
  • 23. Modeling the Neurobehavioral Consequences of Blast-Induced Traumatic Brain Injury Spectrum Disorder and Identifying Related Biomarkers
    Denes V Agoston and Alaa Kamnaksh.
    • 23.1. INTRODUCTION
    • 23.2. EXPERIMENTAL MODELING OF bTBI
    • 23.3. METHODOLOGY
    • 23.4. SPECIAL CONSIDERATIONS FOR bTBI MODELING
    • 23.5. NEUROBEHAVIORAL CONSEQUENCES OF bTBI
    • 23.6. NEUROBEHAVIORAL OUTCOMES IN EXPERIMENTAL AND CLINICAL bTBI
    • 23.7. BIOMARKERS IN bTBI
    • 23.8. IMAGING BIOMARKERS IN CLINICAL bTBI
    • 23.9. IMAGING BIOMARKERS IN EXPERIMENTAL bTBI
    • 23.10. THE IMPORTANCE OF CORRELATING BETWEEN NEUROBEHAVIOR AND IMAGING
    • 23.11. BLOOD- AND CSF-BASED PROTEIN BIOMARKERS
    • 23.12. BIOMARKER IDENTIFICATION AND CHOICE OF ASSAY PLATFORM
    • 23.13. CONCLUDING REMARKS
    • REFERENCES
  • 24. Magnetic Resonance Imaging Application in the Area of Mild and Acute Traumatic Brain Injury: Implications for Diagnostic Markers?
    Arnold Toth.
    • 24.1. INTRODUCTION
    • 24.2. ROUTINE MRI METHODS IN mTBI
    • 24.3. ADVANCED MRI METHODS IN mTBI
    • 24.4. CONCLUSION AND PERSPECTIVES
    • REFERENCES
  • 25. Translational Metabolomics of Head Injury: Exploring Dysfunctional Cerebral Metabolism with Ex Vivo NMR Spectroscopy-Based Metabolite Quantification
    Stephanie M Wolahan, Daniel Hirt, and Thomas C Glenn.
    • 25.1. INTRODUCTION TO METABOLOMICS
    • 25.2. METABOLIC CHANGES AFTER TBI AND CURRENT TREATMENT RECOMMENDATIONS
    • 25.3. METABOLOMICS OF HEAD INJURY
    • 25.4. EXPERIMENTAL PERSPECTIVE ON NMR-BASED METABOLOMICS APPLIED TO HEAD INJURY
    • 25.5. CONCLUSION
    • REFERENCES
  • 26. The Emerging Impact of microRNAs in Neurotrauma Pathophysiology and Therapy
    Oneil G Bhalala.
    • 26.1. INTRODUCTION
    • 26.2. miRNA BIOGENESIS AND FUNCTION
    • 26.3. THE DYNAMIC ROLES OF miRNAs IN CNS DEVELOPMENT
    • 26.4. miRNAs AS A MEANS TO UNDERSTAND NEUROTRAUMA PATHOPHYSIOLOGY
    • 26.5. OVERLAP OF STROKE AND TBI miRNA PROFILES
    • 26.6. THE THERAPEUTIC POTENTIAL OF miRNAs
    • 26.7. CONCLUDING REMARKS
    • REFERENCES
  • 27. Neuroproteome Dynamics in Modeled Brain Injury: A Systems Neurobiology Perspective
    Pavel N Lizhnyak, Hiyab Yohannes, and Andrew K Ottens.
    • 27.1. INTRODUCTION TO NEUROPROTEOMICS IN MODELED BRAIN INJURY
    • 27.2. STUDY DESIGN IN UNBIASED NEUROPROTEOMICS OF TBI
    • 27.3. QUANTITATIVE ANALYSIS
    • 27.4. NEUROPROTEOME DYNAMICS AND DISCLOSING NEW KNOWLEDGE
    • 27.5. CONCLUSION
    • REFERENCES
  • 28. Gene Interaction Hierarchy Analysis Can Be an Effective Tool for Managing Big Data Related to Unilateral Traumatic Brain Injury
    Todd E White and Byron D Ford.
    • 28.1. INTRODUCTION
    • 28.2. DETERMINING GOIs
    • 28.3. COMPILING THE GIH
    • 28.4. OPTIMIZING THE GIH ANALYSIS
    • 28.5. DISCUSSION
    • 28.6. METHODS
    • ACKNOWLEDGMENTS
    • REFERENCES
  • 29. Autoantibodies in CNS Trauma and Neuropsychiatric Disorders: A New Generation of Biomarkers
    Firas Kobeissy and Rabih A Moshourab.
    • 29.1. INTRODUCTION
    • 29.2. BBB, IMMUNE SYSTEM, MOLECULAR MIMICRY, AND CNS INTERACTION
    • 29.3. AUTOANTIBODIES GENESIS AND MECHANISMS IN THE CNS: AGING PROCESS
    • 29.4. NEUROPROTECTIVE ROLE OF AUTOANTIBODIES
    • 29.5. AUTOANTIBODIES IN TBI
    • 29.6. SCI, B LYMPHOCYTES, AND THE PERPLEXING ROLE OF AUTOANTIBODIES
    • 29.7. PATHOGENIC ROLE OF SCI AUTOANTIBODIES AND SCI LEVEL DEPENDENCE
    • 29.8. B-LYMPHOCYTES AS THERAPEUTIC TARGETS POST-SCI
    • 29.9. AUTOANTIBODIES IN AUTISM SPECTRUM DISORDER
    • 29.10. AUTOANTIBODIES IN THE AREA OF NEUROTOXICITY
    • 29.11. AUTOANTIBODIES IN THE AREA OF PARANEOPLASTIC SYNDROMES
    • 29.12. CONCLUSION
    • ACKNOWLEDGMENT
    • REFERENCES
  • 30. Systems Biology Applications to Decipher Mechanisms and Novel Biomarkers in CNS Trauma
    Chenggang Yu and Firas Kobeissy.
    • 30.1. INTRODUCTION
    • 30.2. THE APPROACHES OF SYSTEMS BIOLOGY
    • 30.3. SYSTEMS BIOLOGY IN NEUROTRAUMA STUDIES
    • 30.4. CONCLUSION
    • REFERENCES
• V. Neurocognitive and Neurobehavioral Topics in Brain Injury
  • 31. Neuropathology of Mild Traumatic Brain Injury: Correlation to Neurocognitive and Neurobehavioral Findings
    Erin D Bigler.
    • 31.1. INTRODUCTION
    • 31.2. CT AND MRI IN mTBI
    • 31.3. EMPIRICALLY DERIVED QUANTITATIVE MRI ABNORMALITIES
    • 31.4. MICROSTRUCTURE EFFECTS OF mTBI
    • 31.5. NETWORK DAMAGE AND DISRUPTION IN mTBI
    • 31.6. HETEROGENEITY OF THE LESION
    • 31.7. UNIQUENESS OF EACH MTBI “LESION” TO DISRUPT THE NETWORK
    • 31.8. TIME SEQUENCE OF NEUROPATHOLOGY ASSOCIATED WITH mTBI
    • 31.9. CELLULAR BASIS OF mTBI NEUROPATHOLOGY
    • 31.10. VOLUMETRY FINDINGS IN mTBI
    • 31.11. CONCLUSION
    • REFERENCES
  • 32. Blast-Related Mild Traumatic Brain Injury: Neuropsychological Evaluation and Findings
    Nathaniel W Nelson, Nicholas D Davenport, Scott R Sponheim, and Carolyn R Anderson.
    • 32.1. INTRODUCTION
    • 32.2. CONVENTIONAL (NONBLAST) mTBI (CONCUSSION)
    • 32.3. BLAST-RELATED mTBI (CONCUSSION)
    • 32.4. STRUCTURAL NEUROIMAGING OF BLAST-RELATED mTBI
    • 32.5. CONCLUSION AND FUTURE DIRECTIONS
    • Appendix 32.A. MINNESOTA BLAST EXPOSURE SCREENING TOOL (MN-BEST)
    • ACKNOWLEDGMENT
    • REFERENCES
  • 33. Persistent Cognitive Deficits: Implications of Altered Dopamine in Traumatic Brain Injury
    Hong Qu Yan, Nicole D Osier, Jonathan Korpon, James W Bales, Anthony E Kline, Amy K Wagner, and C. Edward Dixon.
    • 33.1. INTRODUCTION
    • 33.2. EVIDENCE FOR A ROLE OF DA IN BRAIN INJURY
    • 33.3. IMPLICATIONS OF ALTERED DA
    • 33.4. COGNITIVE IMPLICATIONS OF ALTERED DA
    • 33.5. TARGETING DA DIRECTLY
    • 33.6. INDIRECTLY TARGETING DA
    • 33.7. OPPORTUNITIES FOR ADDITIONAL RESEARCH
    • 33.8. CONCLUSION
    • REFERENCES
• VI. Neurorehabilitation and Neuroprotection
  • 34. Rehabilitative Paradigms after Experimental Brain Injury: Relevance to Human Neurotrauma
    Corina O Bondi, Roya Tehranian-DePasquale, Jeffrey P Cheng, Christina M Monaco, Grace S Griesbach, and Anthony E Kline.
    • 34.1. INTRODUCTION
    • 34.2. Environmental Enrichment
    • 34.3. EXERCISE
    • 34.4. LOW-LEVEL LASER THERAPY
    • 34.5. CONSTRAINT-INDUCED MOVEMENT THERAPY
    • 34.6. CONCLUSION
    • REFERENCES
  • 35. Models of Posttraumatic Brain Injury Neurorehabilitation
    Michelle D Failla and Amy K Wagner.
    • 35.1. INTRODUCTION TO EXPERIMENTAL MODELS OF NEUROREHABILITATION
    • 35.2. TBI ANIMAL MODELS: CONSIDERATIONS FOR REHABILITATION
    • 35.3. OVERVIEW OF COMMON ANIMAL MODELS IN TBI
    • 35.4. CHALLENGES IN TRANSLATION BETWEEN ANIMAL MODELS AND CLINICAL TBI
    • 35.5. ANATOMICAL-BEHAVIORAL CORRELATES
    • 35.6. DIFFUSE VERSUS FOCAL INJURY MODELS
    • 35.7. IMPORTANT SIGNALING CASCADES IN NEUROREHABILITATION
    • 35.8. MODELING MOTOR AND BEHAVIORAL DEFICITS
    • 35.9. PRECLINICAL MODELS AND NONPHARMACOLOGICAL REHABILITATION INTERVENTIONS AND CONSTRUCTS
    • 35.10. ENVIRONMENTAL ENRICHMENT
    • 35.11. COGNITIVE REHABILITATION
    • 35.12. PRECLINICAL MODELS AND PHARMACOLOGICAL MANIPULATION OF REHABILITATION CONSTRUCTS
    • 35.13. CONCLUSIONS: REHABILOMICS IN NEUROREHABILITATION RESEARCH
    • REFERENCES
  • 36. Translational Considerations for Behavioral Impairment and Rehabilitation Strategies after Diffuse Traumatic Brain Injury
    Theresa Currier Thomas, Taylor A Colburn, Kelsey Korp, Aida Khodadad, and Jonathan Lifshitz.
    • 36.1. INTRODUCTION
    • 36.2. TYPES OF CLINICAL dTBI AND RESULTING BEHAVIORAL IMPAIRMENTS
    • 36.3. ANIMAL MODELS OF dTBI AND ASSOCIATED BEHAVIORAL DEFICITS
    • 36.4. EVIDENCE FOR CIRCUIT DAMAGE AND RECOVERY FROM EXPERIMENTAL dTBI
    • 36.5. TYPES OF REHABILITATION
    • 36.6. CONSIDERATIONS WHEN CHOOSING CLINICAL REHABILITATION
    • 36.7. CONCLUSION
    • REFERENCES
  • 37. Endothelin, Cerebral Blood Flow, and Traumatic Brain Injury: Implications for a Future Therapeutic Target
    Justin C Graves and Christian W Kreipke.
    • 37.1. INTRODUCTION
    • 37.2. UNDERSTANDING CBF, ITS REGULATION, AND ITS IMPORTANCE TO OUTCOME
    • 37.3. THE ROLE OF ENDOTHELIN IN AUTOREGULATION
    • 37.4. THE ROLE OF ENDOTHELIN IN DYSFUNCTIONAL AUTOREGULATION AFTER TBI
    • 37.5. THE ROLE OF ENDOTHELIN RECEPTORS IN DYSFUNCTIONAL CBF AFTER TBI
    • 37.6. ETA: A THERAPEUTIC TARGET FOR MITIGATING THE DELETERIOUS EFFECTS OF TBI
    • 37.7. CONCLUSION
    • REFERENCES
  • 38. Application of Novel Therapeutic Agents for CNS Injury: NAAG Peptidase Inhibitors
    Bruce G Lyeth.
    • 38.1. INTRODUCTION
    • 38.2. EXCESSIVE GLUTAMATE CONTRIBUTES TO TBI PATHOPHYSIOLOGY
    • 38.3. PEPTIDE NEUROTRANSMITTER: NAAG
    • 38.4. NAAG PEPTIDASE INHIBITORS, NAAG, AND EXCITOTOXICITY
    • 38.5. NAAG PEPTIDASE INHIBITORS APPLIED TO TBI
    • 38.6. ROLE OF NAA IN CNS INJURY
    • 38.7. ELEVATED INTRACELLULAR NA⁺ ADVERSELY AFFECTS ASTROCYTES
    • 38.8. CONCLUSIONS AND PERSPECTIVE
    • REFERENCES
  • 39. Neuregulin-1 and Neurovascular Protection
    Limin Wu, Samantha J Walas, Wendy Leung, Eng H Lo, and Josephine Lok.
    • 39.1. INTRODUCTION
    • 39.2. NRG1/ErbB SIGNALING
    • 39.3. BLOOD–BRAIN BARRIER PERMEABILITY
    • 39.4. AXONAL INJURY
    • 39.5. POSTTRAUMA ISCHEMIC BRAIN INJURY
    • 39.6. POSTTRAUMA INFLAMMATION
    • 39.7. POSTTRAUMA EPILEPSY
    • 39.8. POSTTRAUMATIC COGNITIVE DEFICITS AND NEUROGENESIS
    • 39.9. NRG1 IN CLINICAL TRIALS
    • 39.10. BIVALENT NRG1 DERIVATIVES
    • 39.11. CONCLUSION
    • ACKNOWLEDGMENTS
    • REFERENCES
  • 40. Potential Use of Calpain Inhibitors as Brain Injury Therapy
    Emilio B Cagmat, Joy D Guingab-Cagmat, Anatoliy V Vakulenko, Ronald L Hayes, and John Anagli.
    • 40.1. INTRODUCTION
    • 40.2. THE TARGET: CALPAIN
    • 40.3. STRUCTURE-FUNCTIONAL ASPECTS OF CONVENTIONAL CALPAINS
    • 40.4. CALPAIN INHIBITOR DRUG DEVELOPMENT
    • 40.5. CALPAIN INHIBITORS
    • 40.6. COUNTERSCREENS
    • 40.7. CHALLENGES IN MAKING CALPAIN INHIBITOR TO THE BRAIN
    • 40.8. CONCLUSION
    • REFERENCES
  • 41. Nanoparticles for Neurotherapeutic Drug Delivery in Neurodegenerative Disorders: Application in Neurotrauma
    Mark S Kindy and Alexey Vertegel.
    • 41.1. INTRODUCTION
    • 41.2. CONCLUSIONS
    • REFERENCES
  • 42. Stem Cell Therapy in Brain Trauma: Implications for Repair and Regeneration of Injured Brain in Experimental TBI Models
    Andrew Rolfe and Dong Sun.
    • 42.1. INTRODUCTION
    • 42.2. POTENTIAL OF ENDOGENOUS NSCs FOR BRAIN REPAIR
    • 42.3. STEM CELLS AS CELL SOURCE FOR NEURAL TRANSPLANTATION FOR BRAIN REPAIR AND REGENERATION
    • 42.4. CONCLUSION AND PERSPECTIVES
    • REFERENCES
  • 43. Cortical Stimulation-Induced Structural Plasticity and Functional Recovery after Brain Damage
    DeAnna L Adkins.
    • 43.1. INTRODUCTION
    • 43.2. EFFECTIVENESS OF MOTOR REHABILITATION
    • 43.3. IMPLANTABLE CS DEVICES ENHANCE MOTOR FUNCTION RECOVERY AND DRIVE NEURAL PLASTICITY
    • 43.4. NONINVASIVE CS IMPROVES MOTOR FUNCTION AFTER STROKE AND ALTERS BRAIN FUNCTION
    • 43.5. CORTICAL STIMULATION AFTER TBI
    • 43.6. MODELING MOTOR IMPAIRMENTS AND RECOVERY IN ANIMAL MODELS OF TBI
    • 43.7. POSSIBLE LIMITATIONS OF CS AFTER TBI
    • 43.8. CONCLUSION
    • REFERENCES
  • 44. Cranial Nerve Noninvasive Neuromodulation: New Approach to Neurorehabilitation
    Yuri Danilov, Kurt Kaczmarek, Kimberly Skinner, and Mitchell Tyler.
    • 44.1. INTRODUCTION
    • 44.2. ACQUIRED BRAIN INJURY
    • 44.3. DEMANDS OF NEUROREHABILITATION
    • 44.4. BRIEF HISTORY OF CN-NINM TECHNOLOGY
    • 44.5. CONCEPTUAL FRAMEWORK
    • 44.6. TECHNICAL DESCRIPTION OF THE PoNS DEVICE
    • 44.7. HOW IT WORKS
    • 44.8. CN-NINM TRAINING WITH THE PoNS DEVICE
    • 44.9. SELECTED RESULTS
    • 44.10. CONCLUSION
    • REFERENCES
• VII. Mild Brain Injury and Sport Concussion
  • 45. Blast Injuries and Blast-Induced Neurotrauma: Overview of Pathophysiology and Experimental Knowledge Models and Findings
    Ibolja Cernak.
    • 45.1. INTRODUCTION
    • 45.2. BLAST-BODY AND BLAST-BRAIN INTERACTIONS
    • 45.3. MODIFYING POTENTIAL OF SYSTEMIC CHANGES CAUSED BY BLAST
    • 45.4. REQUIREMENTS FOR BLAST-INDUCED INJURY MODELS
    • 45.5. CHOICE OF MODELS
    • 45.6. Blast-Induced Neurotrauma
    • 45.7. CONCLUSION
    • REFERENCES
  • 46. Animal Models for Concussion: Molecular and Cognitive Assessments—Relevance to Sport and Military Concussions
    Hayde Bolouri and Henrik Zetterberg.
    • 46.1. INTRODUCTION: BACKGROUND AND DEFINITIONS
    • 46.2. SPORTS-RELATED CONCUSSION
    • 46.3. ANIMAL MODELS OF TBI
    • 46.4. EFFECT OF REPEATED CONCUSSION/mTBI
    • 46.5. CONCLUSION AND PERSPECTIVES
    • 46.6. LIMITATIONS
    • REFERENCES
  • 47. The Problem of Neurodegeneration in Cumulative Sports Concussions: Emphasis on Neurofibrillary Tangle Formation
    Vassilis E Koliatsos and Leyan Xu.
    • 47.1. INTRODUCTION
    • 47.2. Conclusions: Critical Issues in CTE and the Role of Experimental Neurobiology
    • REFERENCES
• VIII. Substance Abuse and Comorbid Conditions
  • 48. Evidence for Beneficial and Adverse Effects of Alcohol in Animal Models and Clinical Studies of Traumatic Brain Injury
    Anna N Taylor and Richard L Sutton.
    • 48.1. INTRODUCTION
    • 48.2. ANIMAL STUDIES: ACUTE EtOH EXPOSURE
    • 48.3. ANIMAL STUDIES: CHRONIC EtOH EXPOSURE
    • 48.4. HUMAN STUDIES: ACUTE EFFECTS OF EtOH EXPOSURE
    • 48.5. HUMAN STUDIES: FUNCTIONAL OUTCOMES WITH TBI AND EtOH EXPOSURE AND EFFECTS OF CHRONIC CONSUMPTION
    • REFERENCES
  • 49. Modeling Traumatic Brain Injury-Induced Alterations in Alcohol Use Behaviors
    James P Caruso, Jennifer L Lowing, and Alana C Conti.
    • 49.1. INTRODUCTION
    • 49.2. ETHANOL BEHAVIOR MODELS
    • 49.3. COMPATIBILITY OF TBI MODELS WITH ETHANOL PARADIGMS
    • 49.4. CONCLUSION
    • REFERENCES