Evaluating the effect of post-traumatic hypoxia on the development of axonal injury following traumatic brain injury in sheep.

Damage to the axonal white matter tracts within the brain is a key cause of neurological impairment and long-term disability following traumatic brain injury (TBI). Understanding how axonal injury develops following TBI requires gyrencephalic models that undergo shear strain and tissue deformation similar to the clinical situation and investigation of the effects of post-injury insults like hypoxia. The aim of this study was to determine the effect of post-traumatic hypoxia on axonal injury and inflammation in a sheep model of TBI. Fourteen male Merino sheep were allocated to receive a single TBI via a modified humane captive bolt animal stunner, or sham surgery, followed by either a 15 min period of hypoxia or maintenance of normoxia. Head kinematics were measured in injured animals. Brains were assessed for axonal damage, microglia and astrocyte accumulation and inflammatory cytokine expression at 4 hrs following injury. Early axonal injury was characterised by calpain activation, with significantly increased SNTF immunoreactivity, a proteolytic fragment of alpha-II spectrin, but not with impaired axonal transport, as measured by amyloid precursor protein (APP) immunoreactivity. Early axonal injury was associated with an increase in GFAP levels within the CSF, but not with increases in IBA1 or GFAP+ve cells, nor in levels of TNFα, IL1ß or IL6 within the cerebrospinal fluid or white matter. No additive effect of post-injury hypoxia was noted on axonal injury or inflammation. This study provides further support that axonal injury post-TBI is driven by different pathophysiological mechanisms, and detection requires specific markers targeting multiple injury mechanisms. Treatment may also need to be tailored for injury severity and timing post-injury to target the correct injury pathway.

Assessment of a Non-Invasive Brain Pulse Monitor to Measure Intra-Cranial Pressure Following Acute Brain Injury.

Background: Intracranial pressure (ICP) monitoring requires placing a hole in the skull through which an invasive pressure monitor is inserted into the brain. This approach has risks for the patient and is expensive. We have developed a non-invasive brain pulse monitor that uses red light to detect a photoplethysmographic (PPG) signal arising from the blood vessels on the brain's cortical surface. The brain PPG and the invasive ICP waveform share morphological features which may allow measurement of the intracranial pressure. Methods: We enrolled critically ill patients with an acute brain injury with invasive ICP monitoring to assess the new monitor. A total of 24 simultaneous invasive ICP and brain pulse monitor PPG measurements were undertaken in 12 patients over a range of ICP levels. Results: The waveform morphologies were similar for the invasive ICP and brain pulse monitor PPG approach. Both methods demonstrated a progressive increase in the amplitude of P2 relative to P1 with increasing ICP levels. An automated algorithm was developed to assess the PPG morphological features in relation to the ICP level. A correlation was demonstrated between the brain pulse waveform morphology and ICP levels, R2=0.66, P < 0.001. Conclusion: The brain pulse monitor's PPG waveform demonstrated morphological features were similar to the invasive ICP waveform over a range of ICP levels, these features may provide a method to measure ICP levels. Trial Registration: ACTRN12620000828921.

Center of mass and anatomical coordinate system definition for sheep head kinematics, with application to ovine models of traumatic brain injury.

Pathological outcomes of traumatic brain injury (TBI), including diffuse axonal injury, are influenced by the direction, magnitude, and duration of head acceleration during the injury exposure. Ovine models have been used to study injury mechanics and pathological outcomes of TBI. To accurately describe the kinematics of the head during an injury exposure, and better facilitate comparison with human head kinematics, anatomical coordinate systems (ACS) with an origin at the head or brain center of mass (CoM), and axes that align with the ovine Frankfort plane equivalent, are required. The aim of this study was to determine the mass properties of the sheep head and brain, and define an ACSvirtual for the head and brain, using anatomical landmarks on the skull with the aforementioned origins and orientation. Three-dimensional models of 10 merino sheep heads were constructed from computed tomography images, and the coordinates of the head and brain CoMs, relative to a previously reported sheep head coordinate system (ACSphysical ), were determined using the Hounsfield unit-mass density relationship. The ACSphysical origin was 34.8 ± 3.1 mm posterosuperior of the head CoM and 43.7 ± 1.7 anteroinferior of the brain CoM. Prominent internal anatomical landmarks were then used to define a new ACS (ACSvirtual ) with axes aligned with the Frankfort plane equivalent and an origin 10.4 ± 3.2 mm from the head CoM. The CoM and ACSvirtual defined in this study will increase the potential for comparison of head kinematics between ovine models and humans, in the context of TBI.

Beyond the Brain: Peripheral Interactions after Traumatic Brain Injury.

Traumatic brain injury (TBI) is a leading cause of death and disability, and there are currently no pharmacological treatments known to improve patient outcomes. Unquestionably, contributing toward a lack of effective treatments is the highly complex and heterogenous nature of TBI. In this review, we highlight the recent surge of research that has demonstrated various central interactions with the periphery as a potential major contributor toward this heterogeneity and, in particular, the breadth of research from Australia. We describe the growing evidence of how extracranial factors, such as polytrauma and infection, can significantly alter TBI neuropathology. In addition, we highlight how dysregulation of the autonomic nervous system and the systemic inflammatory response induced by TBI can have profound pathophysiological effects on peripheral organs, such as the heart, lung, gastrointestinal tract, liver, kidney, spleen, and bone. Collectively, this review firmly establishes TBI as a systemic condition. Further, the central and peripheral interactions that can occur after TBI must be further explored and accounted for in the ongoing search for effective treatments.

Chemical Weapons Exposures in Iraq: Challenges of a Public Health Response a Decade Later.

An October 14, 2014 article in The New York Times reported that the US Department of Defense (DoD) concealed, for nearly a decade, circumstances surrounding service members' exposure to chemical warfare agents (CWA) while deployed to Iraq in support of Operations Iraqi Freedom and New Dawn from March 13, 2003, to December 31, 2011, and alleged failure of the DoD to provide expedient and adequate medical care. This report prompted the DoD to devise a public health investigation, with the Army Public Health Center (Provisional) as the lead agency to identify, evaluate, document, and track CWA casualties of the Iraq war. Further, the DoD revisited and revised clinical guidelines and health policies concerning CWA exposure based on current evidence-based guidelines and best practices.

Postdeployment Respiratory Health Care Encounters Following Deployment to Kabul, Afghanistan: A Retrospective Cohort Study.

Inhalational hazards are numerous in operational environments. A retrospective cohort study was conducted to investigate associations between deployment to Kabul, Afghanistan and subsequent respiratory health among U.S. military personnel. The study population consisted of personnel who deployed to Kabul, select Operation Enduring Freedom locations, personnel stationed in the Republic of Korea, and U.S.-stationed personnel. Incidence rate ratios (IRRs) were estimated for respiratory symptoms, signs, and ill-defined conditions, asthma, and chronic obstructive pulmonary disease. A significantly elevated rate of symptoms, signs, and ill-defined conditions was observed among Kabul-deployed personnel compared to personnel deployed or stationed in Bagram (IRR 1.12; 95% confidence interval [CI], 1.05-1.19), Republic of Korea (IRR 1.20; 95% CI, 1.10-1.31), and the United States (IRR 1.52; 95% CI, 1.43-1.62). A statistically elevated rate of asthma was observed among personnel deployed to Kabul, relative to U.S.-stationed personnel (IRR 1.61; 95% CI, 1.22-2.12). Statistically significant rates were not observed for chronic obstructive pulmonary disease among Kabul-deployed personnel compared to other study groups. These findings suggest that deployment to Kabul is associated with an elevated risk of postdeployment respiratory symptoms and new-onset asthma.

Trends in rates of chronic obstructive respiratory conditions among US military personnel, 2001-2013.

BACKGROUND: The US military has been continuously engaged in combat operations since 2001. Assessing trends in respiratory health diagnoses during this time of prolonged military conflict can provide insight into associated changes in the burden of pulmonary conditions in the US military population. PURPOSE: To estimate and evaluate trends in rates of chronic obstructive pulmonary diseases in the active duty US military population from 2001 through 2013. METHODS: A retrospective analysis of ambulatory medical encounter diagnosis data corresponding to a study base of over 18 million personnel-years was performed to estimate average rates and evaluate temporal trends in rates of chronic obstructive lung conditions. Differences in rates and the time trends of those rates were evaluated by branch of military service, military occupation, and military rank. RESULTS: During the 13-year period, we observed 482,670 encounters for chronic obstructive pulmonary disease and allied conditions (ICD-9 490-496) among active duty military personnel. Over half (57%) of the medical encounters in this category were for a diagnosis of bronchitis, not specified as acute or chronic. There was a statistically significant 17.2% average increase in the annual rates of this nonspecific bronchitis diagnosis from 2001-2009 (95% CI: 13.5% to 21.1%), followed by a 23.6% annual decline in the rates from 2009 through 2013 (95% CI: 8.6% to 36.2%). Statistically significant declines were observed in the rates of chronic bronchitis over time (annual percentage decline: 3.1%; 95% CI: 0.5% to 6.6%) and asthma (annual percentage decline: 5.9%; 95% CI: 2.5% to 9.2%). A 1.6% annual increase in the rate of emphysema and a 0.1% increase in the rate of chronic airways obstruction (not elsewhere classified) over the study period were not statistically significant (P>.05). The magnitude of the estimated rates of these chronic obstructive lung conditions, and, to a lesser extent, the temporal trends in these rates, were sensitive to the requirement that there be persistence of the diagnosis evidenced in the medical record in order qualify as an incident case. CONCLUSIONS: We observed decreases in the rates of asthma and chronic bronchitis over the 13-year study period. The increase, and then decrease, over time in rates of bronchitis that has not been specified as acute or chronic drives the overall trends in chronic respiratory disease trends.

A retrospective cohort study of military deployment and postdeployment medical encounters for respiratory conditions.

Deployed military personnel are exposed to inhalational hazards that may increase their risk of chronic lung conditions. This evaluation assessed associations between Operation Iraqi Freedom (OIF) deployment and postdeployment medical encounters for respiratory symptoms and medical conditions. This retrospective cohort study was conducted among military personnel who, between January 2005 and June 2007, were deployed to either of two locations with burn pits in Iraq, or to either of two locations without burn pits in Kuwait. Incidence rate ratios (IRRs) were estimated using two nondeployed reference groups. Rates among personnel deployed to burn pit locations were also compared directly to those among personnel deployed to locations without burn pits. Significantly elevated rates of encounters for respiratory symptoms (IRR = 1.25; 95% confidence interval [CI]: 1.20-1.30) and asthma (IRR = 1.54; 95% CI: 1.33-1.78) were observed among the formerly deployed personnel relative to U.S.-stationed personnel. Personnel deployed to burn pit locations did not have significantly elevated rates for any of the outcomes relative to personnel deployed to locations without burn pits. These results are consistent with the hypothesis that OIF deployment is associated with subsequent risk of respiratory conditions. Elevated medical encounter rates were not uniquely associated with burn pits.

Assessment of changes in mental health conditions among sailors and marines during postdeployment phase.

Previous research regarding the mental health ramifications of military deployments focused on the U.S. Army population. As part of its deployment health surveillance mission, Navy and Marine Corps Public Health Center conducted a study of the Department of Navy population to identify reported mental health effects associated with Operation Iraqi Freedom, describe mental health care utilization by returning service members previously deployed in support of Operation Iraqi Freedom, and examine the relationships between self-identified risks and provider referral practices. Despite a considerable number of self-reported mental health concerns, referral for mental health consultations and health care utilization were rare. The psychological well-being of service members is essential to the military's optimum functionality and operational readiness; therefore, continued research in this area has significant bearing on future force health protection efforts. Additionally, this study highlights the need for further research on deployment-related mental health concerns.