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Due largely to the use of improvised explosive devices (IEDs) and other explosives in recent military conflicts, blast-related TBI has emerged as a prominent injury sustained by warfighters. In the recent wars in Iraq and Afghanistan, traumatic brain injury (TBI) has been one of the most common types of injury sustained by soldiers and military personnel; of the ~380,000 TBIs reported in service members from 2000 to 2017, 82.3% were classified as mild (mTBI). While mTBI is associated with normal structural imaging, brief or no loss of consciousness, and rapid recovery of mental state, mTBI can nevertheless lead to persistent behavioral and cognitive effects. As in other cases of mTBI, exposure to low-level blast often does not cause immediate overt neurological effects, but may similarly lead to persistent behavioral and cognitive deficits. These effects are likely to be compounded when multiple exposures to blast and/or impact are sustained, since there is increasing evidence that multiple mTBIs can lead to chronic neurodegeneration. One common form of this deleterious outcome is frontotemporal lobar degeneration (FTLD), which is a progressive neurodegenerative process marked by atrophy of the frontal and temporal lobes, leading to frontotemporal dementia, a common form of dementia affecting behavior, cognition and language. About half of all cases of FTLD are marked by TAR-DNA binding protein (TDP-43)-positive protein inclusions. TDP-43, a DNA/RNA binding protein, controls the expression of thousands of genes and is associated with several neurodegenerative diseases including amyotrophic lateral sclerosis, Alzheimer's disease, Huntington's disease, and chronic traumatic encephalopathy. TDP-43 abnormalities have also been associated with traumatic brain injury in both pre-clinical and clinical studies. The role of TDP-43 in the manifestation of FTLD pathology in military TBI cases is currently unclear, and to date there has been only a limited number of pre-clinical studies addressing the effects of repeated blast-related mild TBI (rbTBI) in relation to FTLD and TDP-43. This review will summarize some of these findings and address the concerns and critical knowledge gaps associated with FTLD manifestation with military populations, as well as clinical findings on other forms of mTBI.

Due largely to the use of improvised explosive devices (IEDs) and other explosives in recent military conflicts, blast-related TBI has emerged as a prominent injury sustained by warfighters. In the recent wars in Iraq and Afghanistan, traumatic brain injury (TBI) has been one of the most common types of injury sustained by soldiers and military personnel; of the ~380,000 TBIs reported in service members from 2000 to 2017, 82.3% were classified as mild (mTBI). While mTBI is associated with normal structural imaging, brief or no loss of consciousness, and rapid recovery of mental state, mTBI can nevertheless lead to persistent behavioral and cognitive effects. As in other cases of mTBI, exposure to low-level blast often does not cause immediate overt neurological effects, but may similarly lead to persistent behavioral and cognitive deficits. These effects are likely to be compounded when multiple exposures to blast and/or impact are sustained, since there is increasing evidence that multiple mTBIs can lead to chronic neurodegeneration. One common form of this deleterious outcome is frontotemporal lobar degeneration (FTLD), which is a progressive neurodegenerative process marked by atrophy of the frontal and temporal lobes, leading to frontotemporal dementia, a common form of dementia affecting behavior, cognition and language. About half of all cases of FTLD are marked by TAR-DNA binding protein (TDP-43)-positive protein inclusions. TDP-43, a DNA/RNA binding protein, controls the expression of thousands of genes and is associated with several neurodegenerative diseases including amyotrophic lateral sclerosis, Alzheimer's disease, Huntington's disease, and chronic traumatic encephalopathy. TDP-43 abnormalities have also been associated with traumatic brain injury in both pre-clinical and clinical studies. The role of TDP-43 in the manifestation of FTLD pathology in military TBI cases is currently unclear, and to date there has been only a limited number of pre-clinical studies addressing the effects of repeated blast-related mild TBI (rbTBI) in relation to FTLD and TDP-43. This review will summarize some of these findings and address the concerns and critical knowledge gaps associated with FTLD manifestation with military populations, as well as clinical findings on other forms of mTBI. [ABSTRACT FROM AUTHOR]

A finite element model of the head of a 55-kg Yucatan pig was developed to calculate the incident pressure and corresponding intracranial pressure due to the explosion of 8 lb (3.63 kg) of C4 at three different distances. The results from the model were validated by comparing findings with experimentally obtained data from five pigs at three different blast overpressure levels: low (150 kPa), medium (275 kPa), and high (400 kPa). The peak values of intracranial pressures from numerical model at different locations of the brain such as the frontal, central, left temporal, right temporal, parietal, and occipital regions were compared with experimental values. The model was able to predict the peak pressure with reasonable percentage differences. The differences for peak incident and intracranial pressure values between the simulation results and the experimental values were found to be less than 2.2 and 29.3%, respectively, at all locations other than the frontal region. Additionally, a series of parametric studies shows that the intracranial pressure was very sensitive to sensor locations, the presence of air bubbles, and reflections experienced during the experiments. Further efforts will be undertaken to correlate the different biomechanical response parameters, such as the intracranial pressure gradient, stress, and strain results obtained from the validated model with injured brain locations once the histology data become available. [ABSTRACT FROM AUTHOR]