Duke-UNC ADRC SLAM-DUNC 2022
Blast exposure, a military-related vulnerability that increases dementia risk, produces synaptic compromise and corresponding astrocyte morphology changes in hippocampal explants
Giang MH,1 Almeida MF,1 Farizatto KLG,1 Piehler T,2 and Bahr BA1.
1 Biotechnology Research and Training Center, University of North Carolina – Pembroke, Pembroke, North Carolina
2 U.S. Army Research Laboratory, Aberdeen Proving Ground, Maryland
Age-related dementias are escalating to a crisis of the 21st century. Besides age, additional risks have been linked to neurotrauma, as one report studying >350,000 veterans found mild TBI associated with 2.36-3.05-fold dementia increase (Barnes et al. 2018-JAMA Neurol 75:1055). Multidimensional MRI with histopathology assessment also identified axonal injury in brains of military individuals (Benjamini et al. 2021-Brain 144:800). Using brain explants exposed to detonated military RDX explosives (Smith et al. 2016-Exp Neurol 286:107), our model recently found that the blasts produced dementia-related synaptic pathology and stochastic tau pathology (Almeida et al. 2021-Brain Pathology 31:e12936). Shockwaves produced by the 1.7-g spherical RDX did not cause cell death or neuromorphological alterations, whereas measured reductions in synaptic markers known to be down-regulated in Alzheimer’s disease were significant (synaptophysin, GluA1, synapsin IIb). For synaptic adhesion molecules linked to AD, the blast-induced reduction in NCAM180 was substantial, while NCAM140 and NCAM120 exhibited smaller or no reductions, respectively. Note that RDX shockwaves reduced neuropilar NCAM180, whereas mechanical stress applied to the explant insert did not affect the synaptic marker immunoreactivity (98.4±11.8% of control). Astrocytes within the dense neuropil also expressed distinct alterations: blast-induced enlargement of astrocytic cell bodies and lengthening of primary branches in areas displaying synaptopathy.
Given the prevalence of blasts in war zones and training fields, it is vital to understand the oft-considered invisible actions. Our work continues to identify the distinct structural changes triggered by different types of brain vulnerabilities, the pathogenic signatures involving axonal pathology, dendritic modifications, and neighboring astrocytic events.