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Blast-Induced Neurotrauma Results in Spatially Distinct Gray Matter Alteration alongside Hormonal Alteration1Curtin University, Nedlands, Australia, 2Mercer University, Macon, GA, United States
Synopsis
Blast-induced neurotrauma (BINT) occurs frequently in military personnel, who are also vulnerable to occupational stress. This study compared Canadian Armed Forces members/Veterans with a history of BINT to emergency first responders, performing voxel-based morphometry on T1-weighted images to examine gray matter alteration, and assessment of stress-related hormones to delineate BINT effects from stress. We found widespread, symmetric loci of reduced gray matter volume specific to BINT, which occurred alongside significant increases in testosterone, cortisol and the testosterone/cortisol ratio. These results indicate that BINT may cause structural and endocrine alterations unseen in emergency service workers who experienced occupational stress alone.
Introduction
Blast-induced neurotrauma (BINT) is a form of traumatic brain injury caused by blast waves generated during an explosion1. In contrast to other mechanisms of injury in which the head strikes or is struck by an object (e.g. sports or motor vehicle accidents), BINT is primarily caused by the passage of blast waves directly through the head and body2. BINT is of growing concern in both military and civilian populations due to an increasing prevalence of explosive weaponry in combat and terrorist actions. Among military personnel, repeated mild exposures to blast occur frequently during training and deployment1. BINT events are increasingly recognised to cause long-term neuropsychological and neurocognitive change, and may also result in brain structural alterations, with particular consequences for gray matter. As military occupations are linked to frequent exposures to stress3, BINT might negatively influence the personnel’s stress coping abilities and contribute to chronic stress-induced health impairments. In this study we examined gray matter volumetric change after BINT or chronic stress, and investigated the cooccurrence of salivary testosterone and cortisol changes.Methods
Participants in the BINT group were active Canadian Armed Forces (CAF) personnel and CAF veterans with self-identified exposure to BINT at least 6 months prior to examination (n = 11). The chronic stress group consisted of emergency first responders who experienced similar workplace stressors without exposure to BINT (firefighters, paramedics, corrections officers, n = 8). Saliva samples were collected via passive drool technique on the morning of testing, and analysed for testosterone and cortisol concentrations, with raw concentrations converted to Z scores. The testosterone to cortisol (T/C) ratio (pg/mL) was also calculated to determine their relationship. MRI data were acquired using a 3 Tesla Siemens Prisma scanner (Siemens Healthcare GmbH, Erlangen, Germany) with a 64-channel head coil. Structural T1 weighted anatomical volumes were obtained (axial orientation, TR=2080 ms, TE=4.38 ms, FOV=256 mm, slice thickness =1 mm). T1 images were preprocessed using SPM12, normalized using an affine followed by non-linear registration, corrected for bias field inhomogeneities, registered to standard MNI space and then segmented into gray matter, white matter and cerebrospinal fluid components. Whole-brain voxel based morphometry (VBM) was performed to determine gray matter volume using the Computational Anatomy Toolbox (CAT12)4.Results
Widespread and largely symmetric loci of reduced gray matter volume specific to BINT were found when compared to the chronic stress group. Predominant clusters (Figure 1) were found bilaterally in the superior temporal gyrus, cuneus, thalamus and cerebellum, while significant hemispheric changes were noted in the left middle occipital gyrus and right middle and posterior cingulate. Examination of saliva testosterone and cortisol Z scores (Figures 2A and 2B, respectively) revealed distinct and opposing patterns in the BINT and chronic stress groups, with significantly elevated testosterone levels in the BINT group, and reduced testosterone levels in the chronic stress group. The T/C ratio (Figure 2C) was also significantly increased in the BINT group compared to the chronic stress group, for which values were within the normal range.Conclusion
This study highlights that discrete patterns of gray matter loss occur in anatomically specific brain regions in military personnel after BINT, and that these findings are not observed after chronic stress. The distinct alterations found in the BINT and chronic stress groups with regard to profiles of testosterone, cortisol and their T/C ratio suggest that BINT and chronic stress have differential consequences for HPA axis function. These findings establish that the pathophysiology of blast injury has important structural and endocrine components, and emphasize the distinction between BINT and chronic stress.Acknowledgements
No acknowledgement found.References
1. Cernak I, Noble-Haeusslein LJ. Traumatic brain injury: an overview of pathobiology with emphasis on military populations. J Cereb Blood Flow Metab. 2010 Feb;30(2):255-66. doi: 10.1038/jcbfm.2009.203.
2. Cernak I. Blast Injuries and Blast-Induced Neurotrauma: Overview of Pathophysiology and Experimental Knowledge Models and Findings. In: Kobeissy FH, editor. Brain Neurotrauma: Molecular, Neuropsychological, and Rehabilitation Aspects. Boca Raton (FL): CRC Press/Taylor & Francis; 2015. Chapter 45. Available from: https://www.ncbi.nlm.nih.gov/books/NBK299193/
3. Hellewell SC, Cernak I. Measuring Resilience to Operational Stress in Canadian Armed Forces Personnel. J Trauma Stress. 2018 Feb;31(1):89-101. doi: 10.1002/jts.22261. Epub 2018 Feb 21. PMID: 29465774.
4. Gaser C, Dahnke R, Kurth K, Luders E, Alzheimer’s Disease Neuroimaging Initiative. A Computational Anatomy Toolbox for the Analysis of Structural MRI Data. Neuroimage, in review.
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