Laterality and region-specific tau phosphorylation correlate with PTSD-related behavioral traits in rats exposed to repetitive low-level blast

Garcia, Georgina Perez; Gasperi, Rita De; Sosa, Miguel A. Gama; Perez, Gissel M.; Otero-Pagan, Alena; Pryor, Dylan; Abutarboush, Rania; Kawoos, Usmah; Hof, Patrick R.; Dickstein, Dara L.; Cook, David G.; Gandy, Sam; Ahlers, Stephen T.; Elder, Gregory A.

doi:10.1186/s40478-021-01128-3

Cited by 9 publications

(6 citation statements)

References 104 publications

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“…Animal models show a dose-response curve of blast exposure frequency with tauopathy 71 that results in abnormal neuronal activity and neurobehavioural deficits. [71][72][73][74][75][76][77][78] This work is consistent with our findings which show worse cognitive, somatic, and physical symptoms, neural slowing in the right fronto-temporal and subcortical regions, and lower functional connectivity in the pDMN in those with greater subconcussive load.…”

Section: Neural Slowing In Fronto-temporal and Subcortical Regionssupporting

confidence: 92%

Repetitive subconcussion results in disrupted neural activity independent of concussion history

Solar,

Ventresca,

Zamyadi

et al. 2024

Preprint

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Concussion is a public health crisis which results in a complex cascade of neurochemical changes in the brain that can have life changing consequences. Subconcussions are considered less serious and were overlooked until recently, but we now realise repetitive subconcussions, such as repetitive head impacts, can lead to serious neurological deficits. Subconcussions are common in contact sports, and the military where certain personnel are exposed to repetitive occupational blast overpressure. Postmortem studies in athletes reveal that cumulative duration of play and force from collisions are better predictors than concussion history for the presence and severity of chronic traumatic encephalopathy — a progressive and fatal neurodegenerative tauopathy, distinct from concussion, thought to be caused by repetitive head impacts, and only diagnosable postmortem — thus, an in vivo predictive biomarker would be game changing. Magnetoencephalography has exceptional temporal sampling for imaging the dynamics of neuronal electrochemical action, and functional MRI shows that functional connectivity is associated with tauopathy patterns. Therefore, both imaging modalities could provide a surrogate biomarker of tauopathy. In this cross-sectional study, we examined the effects of repetitive subconcussion on neuronal activity and functional connectivity using magnetoencephalography and functional MRI, and on neurological symptoms and mental health in a military sample. For magnetoencephalography and outcome analyses, 81 participants were split into ′high′ and ′low′ blast exposure groups using the generalized blast exposure value: n=41 high blast (26.4—65.7 years; 4 females); n=40 low blast (28.0—63.3 years; 8 females). For fMRI, two high blast male participants without data were excluded: n=39 (29.6—65.7 years). Magnetoencephalography revealed disrupted neuronal activity in participants with a greater history of repetitive subconcussions, including: neural slowing (excessive delta activity) in the right frontal and temporal lobes and subcortical regions (hippocampus, amygdala, caudate, pallidum, thalamus), and functional dysconnectivity in the posterior default mode network (low and high gamma). Notably, these irregularities were independent of concussion or traumatic stress history, and magnetoencephalography revealed functional dysconnectivity not detected with functional MRI. Besides regional slowing and functional disconnection in crucial brain hubs, those with greater blast exposure had poorer neurological outcomes in somatic and cognitive domains, with no blast-related differences in mental health and no associations between neurological symptoms and neuronal activity. This study suggests that repetitive subconcussions have insidious effects on the brain and that magnetoencephalography provides a potential avenue for both treatment targets by identifying affected brain regions and in prevention by identifying those at risk of cumulative subconcussive neurotrauma.

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Section: Neural Slowing In Fronto-temporal and Subcortical Regionssupporting

confidence: 92%

Repetitive subconcussion results in disrupted neural activity independent of concussion history

Solar,

Ventresca,

Zamyadi

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…p-Tau in our rat model was increased in the anterior cortex and hippocampus, including prelimbic cortex, but not in the amygdala or posterior cortex [33,186]. These correlations are significant in suggesting that p-tau accumulation in anterior neocortical regions and hippocampus may lead to disinhibited amygdala function without p-tau elevation in the amygdala itself.…”

Section: Perivascular Tau Following Bintmentioning

confidence: 57%

“…Particularly striking were the asymmetrical effects on the right and left hippocampus. p-Tau levels further correlated with blast-induced behavioral traits [186]. Elevated p-tau Thr181 in anterior neocortical regions and right hippocampus correlated with anxiety as well as fear learning and novel object localization.…”

Section: Perivascular Tau Following Bintmentioning

confidence: 85%

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The Neurovascular Unit as a Locus of Injury in Low-Level Blast-Induced Neurotrauma

Elder,

Gama Sosa,

De Gasperi

et al. 2024

IJMS

Self Cite

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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.

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“…A maladaptive glial response like the one previously described in neuropsychiatric pathologies was hypothesized to act as a mediator for abnormal neurological COVID-19 aftermath [ 58 ]. Another connection between long neuroCOVID and mental-health disorders could be the functional impairment of the glial cells and the tau protein, known to occur in PTSD [ 59 , 60 , 61 ].…”

Section: Neurological Impairment In Covid-19mentioning

confidence: 99%

Neurological Manifestations of SARS-CoV2 Infection: A Narrative Review

et al. 2022

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The COVID-19 virus frequently causes neurological complications. These have been described in various forms in adults and children. Headache, seizures, coma, and encephalitis are some of the manifestations of SARS-CoV-2-induced neurological impairment. Recent publications have revealed important aspects of viral pathophysiology and its involvement in nervous-system impairment in humans. We evaluated the latest literature describing the relationship between COVID-19 infection and the central nervous system. We searched three databases for observational and interventional studies in adults published between December 2019 and September 2022. We discussed in narrative form the neurological impairment associated with COVID-19, including clinical signs and symptoms, imaging abnormalities, and the pathophysiology of SARS-CoV2-induced neurological damage.

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Laterality and region-specific tau phosphorylation correlate with PTSD-related behavioral traits in rats exposed to repetitive low-level blast

Cited by 9 publications

References 104 publications

Repetitive subconcussion results in disrupted neural activity independent of concussion history

Repetitive subconcussion results in disrupted neural activity independent of concussion history

The Neurovascular Unit as a Locus of Injury in Low-Level Blast-Induced Neurotrauma

Neurological Manifestations of SARS-CoV2 Infection: A Narrative Review

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