PTSD as an Endothelial Disease: Insights From COVID-19

Sfera, Adonis; Osorio, Carolina; Rahman, Leah; Campo, Carlos Manuel Zapata-Martín del; Maldonado, Jose Campo; Jafri, Nyla; Cummings, Michael; Maurer, Steve; Kozlakidis, Zisis

doi:10.3389/fncel.2021.770387

Cited by 13 publications

(13 citation statements)

References 308 publications

(346 reference statements)

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“…The association between PTSD with BBB permeability has been a subject of growing interest. BBB disruption seems to significantly influence the pathophysiology of PTSD, and PTSD is associated with increased BBB permeability, possibly contributing to the development of cognitive dysfunction and other symptoms associated with the disorder [ 51 , 52 , 53 ]. Multiple mechanisms clarifying the link between PTSD and BBB permeability have been advanced.…”

Section: Discussionmentioning

confidence: 99%

The Relationship between Post-Traumatic Stress Disorder Due to Brain Injury and Glutamate Intake: A Systematic Review

Gruenbaum,

Zlotnik,

Oleshko

et al. 2024

Nutrients

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There is a growing body of evidence that suggests a connection between traumatic brain injury (TBI) and subsequent post-traumatic stress disorder (PTSD). While the exact mechanism is unknown, we hypothesize that chronic glutamate neurotoxicity may play a role. The consumption of dietary glutamate is a modifiable factor influencing glutamate levels in the blood and, therefore, in the brain. In this systematic review, we explored the relationship between dietary glutamate and the development of post-TBI PTSD. Of the 1748 articles identified, 44 met the inclusion criteria for analysis in this review. We observed that individuals from countries with diets traditionally high in glutamate had greater odds of developing PTSD after TBI (odds ratio = 15.2, 95% confidence interval 11.69 to 19.76, p < 0.01). These findings may support the hypothesis that chronically elevated blood glutamate concentrations caused by high dietary intake invoke neurodegeneration processes that could ultimately result in PTSD. Further studies will clarify whether lowering glutamate via diet would be an effective strategy in preventing or treating post-TBI PTSD.

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Section: Discussionmentioning

confidence: 99%

The Relationship between Post-Traumatic Stress Disorder Due to Brain Injury and Glutamate Intake: A Systematic Review

Gruenbaum,

Zlotnik,

Oleshko

et al. 2024

Nutrients

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“…Together, this is strong evidence of PS-induced endothelial dysfunction in cerebral circulation. Endothelial dysfunction, the impaired endothelium-dependent dilation of blood vessels, is considered to be both a cardiovascular disease marker and a pathogenetic factor contributing to the development and progression of cardio- and cerebrovascular disease, including stroke [ 34 , 35 ]. Endothelial dysfunction is caused by impaired basal and stimulated release and activity of nitric oxide (NO) that functions as a powerful vasodilator, an inhibitor of platelet and leukocyte aggregation, and an anti-inflammatory agent [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Cerebral Blood Flow in Predator Stress-Resilient and -Susceptible Rats and Mechanisms of Resilience

Kondashevskaya

Downey

Tseĭlikman

et al. 2022

IJMS

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Stress-induced conditions are associated with impaired cerebral blood flow (CBF) and increased risk of dementia and stroke. However, these conditions do not develop in resilient humans and animals. Here the effects of predator stress (PS, cat urine scent, ten days) on CBF and mechanisms of CBF regulation were compared in PS-susceptible (PSs) and PS-resilient (PSr) rats. Fourteen days post-stress, the rats were segregated into PSs and PSr groups based on a behavior-related anxiety index (AI). CBF and its endothelium-dependent changes were measured in the parietal cortex by laser Doppler flowmetry. The major findings are: (1) PS susceptibility was associated with reduced basal CBF and endothelial dysfunction. In PSr rats, the basal CBF was higher, and endothelial dysfunction was attenuated. (2) CBF was inversely correlated with the AI of PS-exposed rats. (3) Endothelial dysfunction was associated with a decrease in eNOS mRNA in PSs rats compared to the PSr and control rats. (4) Brain dopamine was reduced in PSs rats and increased in PSr rats. (5) Plasma corticosterone of PSs was reduced compared to PSr and control rats. (6) A hypercoagulation state was present in PSs rats but not in PSr rats. Thus, potential stress resilience mechanisms that are protective for CBF were identified.

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“…These findings suggest that HLA binding and elimination of HHV may protect against PTSD and, conversely, alleles that are unable to bind to HHV may predispose to PTSD. In addition to potential associations with HHV, other viruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the ongoing pandemic, human immunodeficiency virus, and Ebola have been associated with PTSD at rates greater than 30%, purportedly due to direct effects of pathogens on brain microvasculature and/or on brain areas associated with stress-processing such as the hypothalamic-pituitary-adrenal axis and autonomic nervous system ( Sfera et al, 2021 ), systems widely implicated in PTSD ( Neigh and Ali, 2016 ). Finally, as discussed elsewhere ( Katrinli and Smith, 2021 ), HLA may also influence PTSD via non-immune functions including effects on brain plasticity, learning, memory, stress-response, and behavior ( Boulanger, 2009 ; Huh et al, 2000 ; Sankar et al, 2012 ; Yirmiya and Goshen, 2011 ).…”

Section: Discussionmentioning

confidence: 99%