Traumatic brain injury (TBI) remains a significant source of death and permanent disability, contributing to nearly one-third of all injury-related deaths in the United States and exacting a profound personal and economic toll.

Despite the increased resources that have recently been brought to bear to improve our understanding of TBI, the development of new diagnostic and therapeutic approaches has been disappointingly slow.

Translational Research in Traumatic Brain Injury attempts to integrate expertise from across specialties to address knowledge gaps in the field of TBI. Its chapters cover a wide scope of TBI research in five broad areas:

• • Epidemiology
• • Pathophysiology
• • Diagnosis
• • Current treatment strategies and sequelae
• • Future therapies

Specific topics discussed include the societal impact of TBI in both the civilian and military populations, neurobiology and molecular mechanisms of axonal and neuronal injury, biomarkers of traumatic brain injury and their relationship to pathology, neuroplasticity after TBI, neuroprotective and neurorestorative therapy, advanced neuroimaging of mild TBI, neurocognitive and psychiatric symptoms following mild TBI, sports-related TBI, epilepsy and PTSD following TBI, and more.

The book integrates the perspectives of experts across disciplines to assist in the translation of new ideas to clinical practice and ultimately to improve the care of the brain-injured patient.

Contents

• Series Preface
• Preface
• Editors
• Contributors
• 1. Epidemiology
  Peter Leo and Michael McCrea.
  • INTRODUCTION
  • TBI IN CIVILIAN POPULATIONS
  • TBI IN THE MILITARY POPULATION
  • CONCLUSIONS
  • REFERENCES
• 2. Sport-Related Traumatic Brain Injury
  Michael Clark and Kevin Guskiewicz.
  • INTRODUCTION
  • DEFINITIONS AND NOMENCLATURE
  • SIGNS AND SYMPTOMS
  • PATHOPHYSIOLOGY
  • BIOMECHANICS
  • EPIDEMIOLOGY
  • EVALUATION
  • TREATMENT
  • FUTURE DIRECTIONS IN RESEARCH
  • CONCLUSION
  • REFERENCES
• 3. Diffuse Axonal Injury
  Erik Su and Michael Bell.
  • CLINICAL FEATURES
  • INITIAL INJURY AND PRIMARY AXOTOMY
  • SECONDARY AXOTOMY AND DISRUPTED NEURONAL HOMEOSTASIS
  • NEUROINFLAMMATION
  • EVOLUTION OF DAI AND PLASTICITY
  • SPECIAL CONSIDERATIONS: BLAST INJURY, CHRONIC TRAUMATIC ENCEPHALOPATHY, AND ABUSIVE HEAD TRAUMA
  • MECHANISTICS
  • ANIMAL MODELS
  • GYRENCEPHALIC MODELS
  • BLAST INJURY
  • LISSENCEPHALIC MODELS
  • BIOMARKER ASSAYS
  • NEUROIMAGING IN DIFFUSE AXONAL INJURY
  • ELECTROPHYSIOLOGY AND MAGNETOENCEPHALOGRAPHY
  • THERAPEUTICS
  • SUMMARY
  • REFERENCES
• 4. Blood–Brain Barrier Pathophysiology following Traumatic Brain Injury
  Lulit Price, Christy Wilson, and Gerald Grant.
  • BLOOD–BRAIN BARRIER: THE NEUROVASCULAR UNIT
  • TRAUMATIC BRAIN INJURY: PRIMARY AND SECONDARY INJURY
  • TBI AND THE BBB
  • ROLE OF BLOOD-BORNE FACTORS THAT AFFECT BBB FUNCTION FOLLOWING TBI
  • IMPORTANCE IN DEVELOPMENT OF CEREBRAL EDEMA FOLLOWING TBI
  • STRATEGIES TO REDUCE CEREBRAL EDEMA AFTER TBI
  • NOVEL THERAPEUTIC STRATEGIES TO STABILIZE BBB AFTER TBI
  • STEM CELLS AND BBB RESCUE FOLLOWING TBI
  • CONCLUSIONS
  • ACKNOWLEDGMENT
  • REFERENCES
• 5. Cellular and Molecular Mechanisms of Secondary Neuronal Injury following Traumatic Brain Injury
  Kamesh Krishnamurthy and Daniel T Laskowitz.
  • EXCITOTOXICITY: THE MOLECULAR RESPONSE TO HEAD INJURY
  • APOPTOSIS: THE CELLULAR RESPONSE TO HEAD INJURY
  • MITOCHONDRIAL INJURY: AN ORGANELLE BRIDGE FROM MOLECULAR TO CELLULAR PATHOLOGY
  • EXCITOTOXICITY-INDUCED ENDOPLASMIC RETICULUM STRESS AND TBI: AN EMERGING THERAPEUTIC TARGET
  • NEUROINFLAMMATION AND TBI: BALANCING NEUROPROTECTION VERSUS NEUROTOXICITY
  • SUMMARY
• 6. Neuroinflammation
  Finnian Hanrahan and Matthew Campbell.
  • INTRODUCTION
  • CEREBRAL EDEMA
  • THE BLOOD-BRAIN BARRIER
  • A DEGREE OF IMMUNE PRIVILEGE
  • MORE THAN A BARRIER IN THE WAY?
  • NEUROINFLAMMATION
  • ADAPTIVE OR MALADAPTIVE?
  • PRECLINICAL MODELS OF NEUROINFLAMMATION
  • ACKNOWLEDGMENTS
  • REFERENCES
• 7. Neurosteroids and Traumatic Brain Injury: Translating Biomarkers to Therapeutics; Overview and Pilot Investigations in Iraq and Afghanistan Era Veterans
  Christine E Marx, Jennifer C Naylor, Jason D Kilts, Charlotte E Dunn, Larry A Tupler, Steven T Szabo, Bruce P Capehart, Rajendra A Morey, Lawrence J Shampine, and Shawn K Acheson.
  • INTRODUCTION
  • NEUROSTEROIDS IN TRAUMATIC BRAIN INJURY (TBI): OVERVIEW OF PRECLINICAL STUDIES
  • NEUROSTEROIDS AND TBI: OVERVIEW OF CLINICAL STUDIES
  • NEUROSTEROIDS AS BIOMARKER CANDIDATES: PILOT INVESTIGATIONS IN IRAQ AND AFGHANISTAN ERA VETERANS WITH A HISTORY OF BLAST-RELATED TBI
  • NEUROSTEROIDS AS THERAPEUTICS: PILOT PROOF-OF-CONCEPT CONTROLLED TRIAL IN IRAQ AND AFGHANISTAN ERA VETERANS WITH A HISTORY OF MILD TBI
  • SUMMARY AND FUTURE DIRECTIONS
  • ACKNOWLEDGMENTS
  • DISCLOSURES
  • REFERENCES
• 8. Neuroplasticity after Traumatic Brain Injury
  YouRong Sophie Su, Anand Veeravagu, and Gerald Grant.
  • NEUROPLASTICITY
  • FUNCTIONAL IMAGING OF TRAUMATIC BRAIN INJURY AND NEUROPLASTICITY
  • PROMISING THERAPEUTICS AFTER TBI
  • CONCLUSION
  • REFERENCES
• 9. Genetic Influences in Traumatic Brain Injury
  Ellen R Bennett, Karin Reuter-Rice, and Daniel T Laskowitz.
  • INTRODUCTION
  • CYTOKINE POLYMORPHISMS AND TRAUMATIC BRAIN INJURY (TBI) OUTCOME
  • APOLIPOPROTEIN E
  • MICROTUBULE-ASSOCIATED PROTEIN TAU AND TBI
  • OTHER GENETIC ASSOCIATIONS AND TBI
  • MITOCHONDRIAL GENES
  • GENETICS OF PEDIATRIC TBI
  • CONCLUSION
  • ACKNOWLEDGMENT
  • REFERENCES
• 10. Modeling Post-Traumatic Epilepsy for Therapy Development
  Giulia Curia, Clifford L Eastman, John W Miller, and Raimondo D’Ambrosio.
  • INTRODUCTION
  • MODEL OPTIMIZATION FOR THERAPY DEVELOPMENT
  • ASSESSING EPILEPSY TREATMENTS WITH FLUID PERCUSSION INJURY-INDUCED PTE
  • TECHNICAL AND METHODOLOGICAL ISSUES IN PTE THERAPY DEVELOPMENT
  • CONCLUSIONS
  • ACKNOWLEDGMENTS
  • REFERENCES
• 11. Translational Principles of Neuroprotective and Neurorestorative Therapy Testing in Animal Models of Traumatic Brain Injury
  Edward D Hall.
  • INTRODUCTION
  • GOALS OF DRUG THERAPIES FOR ACUTE TRAUMATIC BRAIN INJURY (TBI)
  • PREVIOUS TBI CLINICAL TRIALS OF NEUROPROTECTIVE AGENTS AND WHAT WE LEARNED RELEVANT TO THE NEEDS FOR PRECLINICAL DRUG EVALUATION IN ANIMAL MODELS
  • VARIABILITY IN TBI PATHOLOGY AND PATHOPHYSIOLOGY: RATIONALE FOR TESTING NEUROPROTECTIVE OR NEURORESTORATIVE DRUGS IN MULTIPLE TBI MODELS
  • TRAUMATIC BRAIN INJURY AND TRAUMATIC BRAIN INJURY-RELEVANT MODELS
  • ISSUES THAT NEED TO BE ADDRESSED IN PRECLINICAL NEUROPROTECTIVE DRUG EVALUATION
  • REFERENCES
• 12. Biomarkers of Traumatic Brain Injury and Their Relationship to Pathology
  Jin Zhang, Vikram Puvenna, and Damir Janigro.
  • RADIOLOGICAL MARKERS OF TRAUMATIC BRAIN INJURY (TBI) AND THEIR RELATIONSHIP TO SERUM OR CEREBROSPINAL FLUID MARKERS
  • HOW CAN A BLOOD TEST COMPLEMENT MAGNETIC RESONANCE IMAGING OR COMPUTED TOMOGRAPHY?
  • X-RAY COMPUTED TOMOGRAPHY (CT)
  • SERUM AND CEREBROSPINAL FLUID MARKERS FOR TBI IN THE ACUTE SETTING
  • CONVENTIONAL MRI
  • ADVANCED MRI IMAGING
  • FUNCTIONAL MRI
  • MR SPECTROSCOPY
  • SUMMARY
  • REFERENCES
• 13. Advanced Neuroimaging of Mild Traumatic Brain Injury
  Inga K Koerte, Jakob Hufschmidt, Marc Muehlmann, Alexander P Lin, and Martha E Shenton.
  • INTRODUCTION TO NEUROIMAGING OF MILD TRAUMATIC BRAIN INJURY
  • HIGH-RESOLUTION STRUCTURAL MAGNETIC RESONANCE IMAGING
  • SUSCEPTIBILITY-WEIGHTED IMAGING
  • FUNCTIONAL MAGNETIC RESONANCE IMAGING (fMRI) AND RESTING STATE FUNCTIONAL MAGNETIC RESONANCE IMAGING (rsfMRI)
  • DYNAMIC SUSCEPTIBILITY CONTRAST MRI
  • ARTERIAL SPIN LABELING
  • DIFFUSION TENSOR IMAGING
  • MR SPECTROSCOPY
  • POSITRON-EMISSION TOMOGRAPHY
  • SINGLE-PHOTON EMISSION COMPUTER TOMOGRAPHY
  • SUMMARY
  • ACKNOWLEDGMENTS
  • REFERENCES
• 14. Epilepsy after Traumatic Brain Injury
  Kan Ding, Puneet K Gupta, and Ramon Diaz-Arrastia.
  • DEFINITIONS
  • EPIDEMIOLOGY
  • RISK FACTORS
  • MECHANISM
  • CLINICAL PRESENTATION
  • PHYSICAL EXAMINATION
  • DIAGNOSTIC EVALUATION
  • LABORATORY STUDIES
  • RADIOGRAPHIC ASSESSMENT
  • TREATMENT
  • INITIAL MANAGEMENT
  • ONGOING CARE
  • TREATMENT CONTROVERSIES
  • ADDITIONAL CONSIDERATIONS
  • REFERENCES
• 15. Intracranial Pressure Monitoring and Management
  Peter Le Roux.
  • INTRODUCTION
  • INDICATIONS FOR INTRACRANIAL PRESSURE (ICP) MONITORING
  • ICP MONITORING TECHNIQUES
  • SAFETY OF ICP MONITORING
  • ICP AND OUTCOME
  • WHAT IS THE OPTIMAL ICP TREATMENT THRESHOLD?
  • MANAGEMENT OF INCREASED ICP
  • DOES ICP MANAGEMENT INFLUENCE PATIENT OUTCOME?
  • TOWARD A NEW CONCEPT OF ICP TREATMENT
  • ACKNOWLEDGMENTS AND CONFLICTS OF INTEREST
  • REFERENCES
• 16. Post-Traumatic Stress Disorder: Relationship to Traumatic Brain Injury and Approach to Treatment
  Jonathon R Howlett and Murray B Stein.
  • INTRODUCTION
  • EPIDEMIOLOGY OF POST-TRAUMATIC STRESS DISORDER AND TRAUMATIC BRAIN INJURY
  • DIAGNOSIS OF PTSD AND TBI
  • PTSD TREATMENT
  • TREATMENT OF COMORBID PTSD AND TBI
  • CONCLUSIONS
  • REFERENCES
• 17. Traumatic Brain Injury and Potential for Neuromodulation
  Shervin Rahimpour and Shivanand P Lad.
  • INTRODUCTION
  • CURRENT LANDSCAPE
  • TRANSCRANIAL MAGNETIC STIMULATION
  • SHORT-TERM EFFECTS OF REPETITIVE TMS
  • LONG-TERM EFFECTS OF rTMS
  • CORTICAL STIMULATION
  • HUMAN TRIALS OF DIRECT CORTICAL STIMULATION
  • NONINVASIVE STIMULATION FOR POST-TRAUMATIC COGNITIVE SEQUELAE
  • DEEP BRAIN STIMULATION (DBS)
  • DBS FOR POST-TRAUMATIC TREMOR
  • DBS FOR POST-TRAUMATIC DYSTONIA AND PARKINSONISM
  • DBS FOR RECOVERY OF COGNITIVE FUNCTION
  • DBS IN THE MINIMALLY CONSCIOUS STATE
  • DBS FOR POST-TRAUMATIC DEPRESSION
  • DBS FOR POST-TRAUMATIC EPILEPSY
  • CONCLUSIONS
  • REFERENCES
• 18. Enhanced Functional Outcome from Traumatic Brain Injury with Brain–Machine Interface Neuromodulation: Neuroprosthetic Scaling in Relation to Injury Severity
  Dennis A Turner.
  • INTRODUCTION
  • GRAPHICAL NETWORK ANALYSIS OF BRAIN FUNCTION
  • TBI: OPPORTUNITIES TO INTERVENE
  • MILD TBI
  • MODERATE TBI
  • SEVERE TBI
  • BRAIN–MACHINE INTERFACE TO ENHANCE RECOVERY
  • SUMMARY
  • REFERENCES
• 19. Neurocognitive and Psychiatric Symptoms following Mild Traumatic Brain Injury
  Wesley R Cole and Jason M Bailie.
  • NEUROCOGNITIVE SYMPTOMS AND EXPECTED RECOVERY
  • PERSISTENT POSTCONCUSSIVE SYMPTOMS (PPCS)
  • PSYCHOLOGICAL DISTRESS AND MILD TRAUMATIC BRAIN INJURY (MTBI)
  • OTHER VARIABLES IMPACTING NEUROCOGNITIVE AND PSYCHIATRIC OUTCOMES
  • METHODOLOGICAL ISSUES IN ASSESSING PPCS
  • BIOPSYCHOSOCIAL MODEL
  • REFERENCES