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Neuroinflammation at the Grey-White Matter Interface in Active-Duty United States Special Operations Forces

Edlow, B. L.; Tseng, C.-E. J.; Gilmore, N.; McKinney, I. R.; Tromly, S. L.; Deary, K. B.; Hu, C. G.; Healy, B. C.; Mac Donald, C. L.; Dams-O'Connor, K.; Greve, D. N.; Bodien, Y. G.; Perl, D. P.; Hooker, J. M.; Zürcher, N. R.

2024-05-14 neurology
10.1101/2024.05.13.24307070 medRxiv
Show abstract

Emerging evidence from autopsy studies indicates that interface astroglial scarring (IAS) at the grey-white matter junction is a pathological signature of repeated blast brain injury in military personnel. However, there is currently no neuroimaging test that detects IAS, which is a major barrier to diagnosis, prevention, and treatment. In 27 active-duty United States Special Operations Forces personnel with high levels of cumulative blast exposure, we performed translocator protein (TSPO) positron emission tomography (PET) using [11C]PBR28 to detect neuroinflammation at the cortical grey-white matter interface, a neuroanatomic location where IAS has been reported in autopsy studies. TSPO signal in individual Operators was compared to the mean TSPO signal in a control group of 9 healthy civilian volunteers. We identified five Operators with TSPO signal at the cortical grey-white matter interface that was more than two standard deviations above the control mean. Cumulative blast exposure, as measured by the Generalized Blast Exposure Value, did not differ between the five Operators with elevated TSPO signal and the 22 Operators without elevated TSPO signal. While the pathophysiologic link between neuroinflammation and IAS remains uncertain, these observations provide the basis for further investigation into TSPO PET as a potential biomarker of repeated blast brain injury. DisclaimerThe views expressed in this manuscript are entirely those of the authors and do not necessarily reflect the views, policy, or position of the United States Government, Department of Defense, or United States Special Operations Command, or the Uniformed Services University of the Health Sciences.

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