Preface

Traumatic brain injury (TBI) is the leading cause of mortality and morbidity with a high incidence in young people all over the world. Post-concussive syndrome (PCS) is an international public health concern with 5–10% of mild TBI (mTBI) cases experiencing concussion in their lives and about 20% of patients having persistent PCS within 6 months to 1 year after mTBI. There are many advanced techniques and methods for the investigation of brain changes and treatments in TBI patients and each of these techniques provides important insights into pathophysiology due to head injury but may not be limited to conventional methods. This new information emerges to give a broad picture of TBI research and clinical evaluation such as cumulative mild head injury (CMHI), novel neuroimaging findings and biomarkers, neuroprotective treatments, brain cooling, and sedation in TBI patients, as well as neuronal and glial biomarkers.

The first section of the book introduces disease neurobiology and PCS. Chapter 1 "Post-Concussion Syndrome" describes the definition of PCS, classification, and association with brain dysfunction, blood flow regulation, intracranial pressure change, and the role of neuroinflammation, as well as long-term sequelae such as chronic traumatic encephalopathy and treatment. Discussing PCS problems in TBI for the improvement of clinical diagnosis based on several definitions is challenging given subjective and gross aspects of the assessments of PCS, e.g. Glasgow comma scale and loss of conscious. This chapter provides many characteristics of PCS, including classification, association with autonomic nervous system dysfunction, brain changes, and treatment that could serve as a reference resource for further research. Chapter 2 "Neuroprotection, Photoperiod, and Sleep" investigates the neurobiological basis of neuroprotective activation, and correlation with PCS, including sleep. The authors attempt to explain the neurobiological basis of neuroprotective activation, adaptive response to photoperiod possibly due to injury of the suprachiasmatic nucleus, and correlation with post-traumatic symptoms, including sleep, as well as limitations. This chapter provides clues to studying the relationships between neuroprotection and sleep as well as the involved neurotransmission systems.

The second section of the book covers the imaging diagnosis and biomarkers in TBI. Chapter 3 "Cumulative Mild Head Injury (CMHI) in Contact Sports" provides a CMHI review, brain changes, and risk factors. This chapter briefly overviews the structure and neuroanatomy of brain change to illustrate the pathophysiological mechanisms involved in primary and secondary head injuries. Some relatively new imaging perspectives, including diffusion axonal injury, close-head injury, homeostasis irregulation, and tauopathy, are illustrated concisely. Risk factors for all types of CMHI are described further with details for early prevention and cure. Chapter 4 "Neuronal and Glial Biomarkers Research for Traumatic Brain Injury" studies multiple biomarkers, including S-100β, UCH-L1, and GFAP for blood–brain barrier breakdown and neuronal injury. The sensitivity and specificity of each biomarker from published articles as well as the ratio between GFAP and UCH-L1 are reported with confirmative statistical results and table summaries. This chapter gives a full overview of the most promising biomarkers studied as predictors of the severity

of TBI, with a special focus on their nature, location, basal concentrations, and methods by which they can be quantified efficiently in blood samples.

The third section refers to the treatment of and multiple therapeutic strategies in TBI patients. Chapter 5 "Use of Neuroprotective Agents for Traumatic Brain Injury" evaluates more than 12 neuroprotective agents from 32 studies with objective data and statistical analyses. Complete descriptions of significance, improvements, and side effects of each agent are covered in detail with the conclusion that a few agents, including oxygen, cyclosporine A, and rivastigmine use for different phases of TBI, show promising treatment effects. Authoritative statements, comprehensive citations, and confirmation with scientific and solid evidence are strong points of this chapter. Chapter 6 "Direct Brain Cooling in Treating Severe Traumatic Head Injury" addresses the interesting and promising topic of hypothermia as a neuroprotective effect in TBI patients. The benefits of cooling, especially of mild cooling such as brain oxygen level reaching desirable levels and a better Glasgow outcome scale at 6 months follow-up, are described and analyzed scientifically with a new cooling machine D-Brain therapy. This chapter highlights the encouraging results of pilot research on direct focal brain cooling therapy in severe head injury patients with significant clinical outcome results in a mild cooling group due to elevations in oxygenation level of injured and decompressed brain tissues. The last chapter "Sedation in TBI Patients" discusses sedation in TBI as a neurocritical and therapeutic strategy with different assessments. The main pharmacological principles, neurophysiology, and neuropathology of sedatives and analgesics, including propofol, benzodiazepines, and opioids, are outlined and evaluated. Several topics and properties based on new technologies, including physiological indications, status epilepticus treatment, management, monitoring in the neuro-ICU with various scales and neurologic examinations, are integrated for better diagnosis and treatment improvement.

> **Yongxia Zhou, PhD** Imaging Scientist, University of Southern California and Columbia University, Los Angeles, California, USA

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Section 1

Disease Etiology and Post

Concussion Syndrome

### Section 1
