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Traumatic brain injury (TBI) remains one of the leading causes of morbidity and mortality amongst civilians and military personnel globally. Despite advances in our knowledge of the complex pathophysiology of TBI, the underlying mechanisms are yet to be fully elucidated. While initial brain insult involves acute and irreversible primary damage to the parenchyma, the ensuing secondary brain injuries often progress slowly over months to years, hence providing a window for therapeutic interventions. To date, hallmark events during delayed secondary CNS damage include Wallerian degeneration of axons, mitochondrial dysfunction, excitotoxicity, oxidative stress and apoptotic cell death of neurons and glia. Extensive research has been directed to the identification of druggable targets associated with these processes. Furthermore, tremendous effort has been put forth to improve the bioavailability of therapeutics to CNS by devising strategies for efficient, specific and controlled delivery of bioactive agents to cellular targets. Here, we give an overview of the pathophysiology of TBI and the underlying molecular mechanisms, followed by an update on novel therapeutic targets and agents. Recent development of various approaches of drug delivery to the CNS is also discussed.

Objective:The aim of this study was to evaluate the effects of secondary tasks on the driving performance of individuals with mild traumatic brain injuries (TBIs).Background:Studies suggest detrimental impacts of driving with TBI or while distracted but the impact of driver distraction on TBI drivers is not well documented.Method:Bayesian regression models were used to estimate the effect of relatively simple secondary tasks on driving performance of TBI and healthy control (HC) drivers. A driving simulator was used to develop prior distribution of task effects on driving performance for HCs. An on-road study was conducted with TBI and HC drivers to generate effect estimates for the posterior distributions. The Bayesian models were also compared to frequentist models.Results:During a coin-sorting task, all drivers exhibited larger maximum lateral acceleration and larger standard deviation of speed than in a baseline driving segment. There were no significant driving performance differences between the TBI and the HC drivers during the tasks. Across all tasks, TBI drivers spent more time looking at the tasks and made more frequent glances toward the tasks.Conclusions:The findings show that even drivers with mild TBI have significantly longer and more glances toward the tasks compared to the HCs.Application:This study demonstrates a Bayesian approach and how the results differ from frequentist statistics. Using prior distributions in a Bayesian model helps account for the probabilities associated with otherwise unknown parameters. This method strengthens the Bayesian parameter estimates compared to that of a frequentist model.

Background: Military service members and veterans face health issues related to traumat-ic brain injury (TBI), especially during combat, use of heavy equipment, and exposures to environmental hazards and explosives. There were 1.000 TBIs reported in deployed Ukra-nian troops during Russian-Ukranian war in 2014–2017. Studies have indicated that some manual therapies could be helpful for treating patients who have post-concussive syndrome. Objective: This case series report de-scribes the effects of CranioSacral Therapy (CST), Visceral Manipulation (VM), and Neu-ro-muscular Manipulation (NM) modalities for treating patients who have post-concussion syndrome. The goal of this study was to evalu-ate these effects on immobility, pain intensity, quality of life, sleep disorders, and cognition in these patients. Materials and Methods: This single-blind-ed case series was conducted at the Volunteer rehabilitation center, Dnipro, Ukraine. The pa-tients were 45 male participationers of Ukra-nian military forces who had been medically diagnosed with post-concussion syndrome. Each participant received a morning and af-ternoon 1-hour session of these three spe-cific manual therapies, which were capable of accessing and addressing the structural, vascular, and neuro-muscular tissues of the Cranium, Neck, Diafragm, Peritoneal bag and brain-as well addressing far-reaching ramifi-cations throughout the body following trauma. The main outcome measures were scores on the: Impact Neurocognitive Test; Blood Oxigen Saturation Test; Short Form-36 Quality of Life Survey, Headache Impact Test, a numeric pain rating scale; orthopedic range of motion tests (ROM); and vestibular testing. Hours of sleep were also checked. These outcome measures were registered at baseline, after treatment, and after a 3–6-month follow up. Results: Statistically significant differenc-es were seen with a decrease in overall pain rating scale scores (P = 0.034), and cranio-cer-vicogenic pain levels decreased (P = 0.047). There were statistically significant increases of blood oxigen saturation (P = 0.033), Mem-ory Test (P = 0.017) scores, and cervical ROM scores (P = 0.036). Hours of sleep averaged 1 hours on the first day of treatment and in-creased to 2.0 hours at the end of treatment. Results were continuing to increase, as noted at a 5-month evaluation. Conclusions: Six sessions of specific CST/VM/NM therapy resulted in statistically great-er improvements in pain intensity, ROM, mem-ory, cognition, blood oxigen saturation and breathing in concussed patients.

Mild Traumatic Brain Injuries (mTBIs) and Post Traumatic Stress Disorder (PTSD) are two of the signature wounds of war. Due to the advances in technology the survival rates are higher than in previous wars, however, the weaponry has changed. The world has seen an increase in the use of suicide bombs, improvised explosive devices (IEDs) and rocket propelled grenades (RPGs) which increases the number of blast related injuries. One of the major problems with blast related injuries is that they can be invisible to the naked eye. The lack of physical evidence suggests the soldier is not injured and can be sent back into battle, when there could be an undetected internal injury. Due to the overlap in symptoms, many soldiers are being treated for PTSD instead of mTBI, which can cause long-term damage. In order to shed light on this issue, this thesis evaluates 2007-2008 active duty medical costs to determine the costs the PTSD and mTBI. The findings suggest that mTBI and PTSD account for .53% and 1.8%, respectively, of the 2008 population data sample. While this may seem like a small percentage this was only two months of data. However, it is important to properly diagnose mTBI and PTSD because these illnesses could cost the military member thousands of dollars in out of pocket medical costs.

"A report prepared for the Massachusetts State Legislature, House Ways and Means Committee, Senate Ways and Means Committee."

In the military, explosive blasts are a significant cause of mild traumatic brain injuries (mTBIs). The symptoms associated with blast mTBIs causes significant economic burdens and a diminished quality of life for many service members. At present, the distinction of the injury mechanism (blast versus non-blast) may not influence TBI diagnosis. However, using noninvasive imaging, this study reveals significant distinctions between the blast and non-blast TBI mechanisms. A cortical whole-brain thickness analysis was performed using structural high-resolution T1-weighted MRI to identify the effects of blasts in persistent mTBI (pmTBI) subjects. A total of 41 blast pmTBI subjects were individually age- and gender-matched to 41 non-blast pmTBI subjects. Using FreeSurfer, cortical thickness was quantified for the blast group, relative to the non-blast group. Cortical thinning was identified within the blast mTBI group, in two clusters bilaterally. In the left hemisphere, the cluster overlapped with the lateral orbitofrontal, rostral middle frontal, medial orbitofrontal, superior frontal, rostral anterior cingulate and frontal pole cortices (p < 0.02, two-tailed, size = 1680 mm(2)). In the right hemisphere, the cluster overlapped with the lateral orbitofrontal, rostral middle frontal, medial orbitofrontal, pars orbitalis, pars triangularis and insula cortices (p < 0.002, two-tailed, cluster size = 2453 mm(2)). Self-report assessments suggest significant differences in the Post-Traumatic Stress Disorder Checklist-Civilian Version (p < 0.05, Bonferroni-corrected) and the Neurobehavioral Symptom Inventory (p < 0.01, uncorrected) between the blast and non-blast mTBI groups. These results suggest that blast may cause a unique injury pattern related to a reduction in cortical thickness within specific brain regions which could affect symptoms. No other study has found cortical thickness difference between blast and non-blast mTBI groups and further replication is needed to confirm these initial observations.