Review Effects of Low-Level Blast on Neurovascular Health and Cerebral Blood Flow: Current Findings and Future Opportunities in Neuroimaging, 2024

Effects of Low-Level Blast on Neurovascular Health and Cerebral Blood Flow: Current Findings and Future Opportunities in Neuroimaging
Kilgore, Madison O.; Hubbard, W. Brad

Low-level blast (LLB) exposure can lead to alterations in neurological health, cerebral vasculature, and cerebral blood flow (CBF). The development of cognitive issues and behavioral abnormalities after LLB, or subconcussive blast exposure, is insidious due to the lack of acute symptoms. One major hallmark of LLB exposure is the initiation of neurovascular damage followed by the development of neurovascular dysfunction. Preclinical studies of LLB exposure demonstrate impairment to cerebral vasculature and the blood–brain barrier (BBB) at both early and long-term stages following LLB. Neuroimaging techniques, such as arterial spin labeling (ASL) using magnetic resonance imaging (MRI), have been utilized in clinical investigations to understand brain perfusion and CBF changes in response to cumulative LLB exposure.

In this review, we summarize neuroimaging techniques that can further our understanding of the underlying mechanisms of blast-related neurotrauma, specifically after LLB. Neuroimaging related to cerebrovascular function can contribute to improved diagnostic and therapeutic strategies for LLB. As these same imaging modalities can capture the effects of LLB exposure in animal models, neuroimaging can serve as a gap-bridging diagnostic tool that permits a more extensive exploration of potential relationships between blast-induced changes in CBF and neurovascular health.

Future research directions are suggested, including investigating chronic LLB effects on cerebral perfusion, exploring mechanisms of dysautoregulation after LLB, and measuring cerebrovascular reactivity (CVR) in preclinical LLB models.

Link | PDF (International Journal of Molecular Sciences)

 

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The Neurovascular Unit as a Locus of Injury in Low-Level Blast-Induced Neurotrauma (2024)
Elder, Gregory A.; Gama Sosa, Miguel A.; De Gasperi, Rita; Perez Garcia, Georgina; Perez, Gissel M.; Abutarboush, Rania; Kawoos, Usmah; Zhu, Carolyn W.; Janssen, William G. M.; Stone, James R.; Hof, Patrick R.; Cook, David G.; Ahlers, Stephen T.

Blast-induced neurotrauma has received much attention over the past decade. Vascular injury occurs early following blast exposure. Indeed, in animal models that approximate human mild traumatic brain injury or subclinical blast exposure, vascular pathology can occur in the presence of a normal neuropil, suggesting that the vasculature is particularly vulnerable.

Brain endothelial cells and their supporting glial and neuronal elements constitute a neurovascular unit (NVU). Blast injury disrupts gliovascular and neurovascular connections in addition to damaging endothelial cells, basal laminae, smooth muscle cells, and pericytes as well as causing extracellular matrix reorganization. Perivascular pathology becomes associated with phospho-tau accumulation and chronic perivascular inflammation. Disruption of the NVU should impact activity-dependent regulation of cerebral blood flow, blood–brain barrier permeability, and glymphatic flow.

Here, we review work in an animal model of low-level blast injury that we have been studying for over a decade. We review work supporting the NVU as a locus of low-level blast injury. We integrate our findings with those from other laboratories studying similar models that collectively suggest that damage to astrocytes and other perivascular cells as well as chronic immune activation play a role in the persistent neurobehavioral changes that follow blast injury.

Link | PDF (International Journal of Molecular Sciences)

 

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Distinct Functional MRI Connectivity Patterns and Cortical Volume Variations Associated with Repetitive Blast Exposure in Special Operations Forces Members (2025)
Andrea Diociasi; Mary A. Iaccarino; Scott Sorg; Emily J. Lubin; Caroline Wisialowski; Amol Dua; Can Ozan Tan; Rajiv Gupta

BACKGROUND
Special operations forces members often face multiple blast injuries and have a higher risk of traumatic brain injury. However, the relationship between neuroimaging markers, the cumulative severity of injury, and long-term symptoms has not previously been well-established in the literature.

PURPOSE
To determine the relationship between the frequency of blast injuries, persistent clinical symptoms, and related cortical volumetric and functional connectivity (FC) changes observed at brain MRI in special operations forces members.

MATERIALS AND METHODS
A cohort of 220 service members from a prospective study between January 2021 and May 2023 with a history of repetitive blast exposure underwent psychodiagnostics and a comprehensive neuroimaging evaluation, including structural and resting-state functional MRI (fMRI). Of these, 212 met the inclusion criteria. Participants were split into two datasets for model development and validation, and each dataset was divided into high-and low-exposure groups based on participants’ exposure to various explosives. Differences in FC were analyzed using a general linear model, and cortical gray matter volumes were compared using the Mann-Whitney U test. An external age-and sex-matched healthy control group of 212 participants was extracted from the SRPBS Multidisorder MRI Dataset for volumetric analyses. A multiple linear regression model was used to assess correlations between clinical scores and FC, while a logistic regression model was used to predict exposure group from fMRI scans.

RESULTS
In the 212 participants (mean age, 43.0 years ± 8.6 [SD]; 160 male [99.5%]) divided into groups with low or high blast exposure, the high-exposure group had higher scores for the Neurobehavioral Symptom Inventory (NSI) (t = 3.16, P < .001) and Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (PCL-5) (t = 2.72, P = .01). FC differences were identified in the bilateral superior and inferior lateral occipital cortex (LOC) (P value range, .001–.04), frontal medial cortex (P < .001), left superior frontal gyrus (P < .001), and precuneus (P value range, .02–.03). Clinical scores from NSI and PCL-5 were inversely correlated with FC in the LOC, superior parietal lobule, precuneus, and default mode networks (r = −0.163 to −0.384; P value range, <.001 to .04). The high-exposure group showed increased cortical volume in regions of the LOC compared with healthy controls and the low-exposure group (P value range, .01–.04). The predictive model helped accurately classify participants into high-and low-exposure groups based on fMRI data with 88.00% sensitivity (95% CI: 78.00, 98.00), 67% specificity (95% CI: 53.00, 81.00), and 73% accuracy (95% CI: 60.00, 86.00).

CONCLUSION
Repetitive blast exposure leads to distinct alterations in FC and cortical volume, which correlate with neurobehavioral symptoms. The predictive model suggests that even in the absence of observable anatomic changes, FC may indicate blast-related trauma.

Link | PDF (Radiology) [Open Access]