Electronic cigarette exposure disrupts blood-brain barrier integrity and promotes neuroinflammation

Heldt, Nathan A.; Seliga, Alecia; Winfield, Malika; Gajghate, Sachin; Reichenbach, Nancy L.; Xiang, Yu; Rom, Slava; Tenneti, Amogha; May, Dana; Gregory, Brian D.; Persidsky, Yuri

doi:10.1016/j.bbi.2020.03.034

Cited by 43 publications

(38 citation statements)

References 101 publications

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“…Notably, because Mint and Mango effects differed, several of our findings point to a “non-nicotine” chemical flavorant component of the JUUL device that may be driving inflammatory changes in the brain. Recent study into the effects of vaping on the blood brain barrier lends further support to this theory, as pro-inflammatory changes were observed, partly independent of nicotine content (38).…”

Section: Discussionmentioning

confidence: 88%

“…In this study, we found that mice exposed to flavored JUUL aerosols may induce significant neuroinflammation in the brain (Figure 8). The nucleus accumbens in particular was found to have elevated levels of inflammatory markers, including TNFα, IL-1β and IL-6 in both NAc-core and NAc-shell, and HMGB1-1 and RAGE in the NAc-shell (38). The NAc-core and NAc-shell contribute to the formation of anxious or depressive behaviors in the context of neuroinflammation via NFκB signaling pathway (39,40).…”

Section: Chronic Juul Inhalation By Inhaled Lps Challenge Does Not Alter Protein Markers Of the Gastrointestinal Tractmentioning

confidence: 99%

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Effect of chronic JUUL aerosol inhalation on inflammatory states of the brain, lung, heart and colon in mice

Moshensky

Brand

Alhaddad³

et al. 2021

Preprint

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While health effects of conventional tobacco are well defined, data on vaping devices, including the most popular e-cigarette JUUL, are less established. Prior acute e-cigarette studies demonstrated inflammatory and cardiopulmonary physiology changes while chronic studies demonstrated extra-pulmonary effects, including neurotransmitter alterations in reward pathways. In this study we investigated effects of chronic flavored JUUL aerosol inhalation on inflammatory markers in brain, lung, heart, and colon. JUUL induced upregulation of cytokine and chemokine gene expression and increased HMGB1 and RAGE in the nucleus accumbens. Inflammatory gene expression increased in colon, and cardiopulmonary inflammatory responses to acute lung injury with lipopolysaccharide were exacerbated in the heart. Flavor-dependent changes in several responses were also observed. Our findings raise concerns regarding long-term risks of e-cigarette use as neuroinflammation may contribute to behavioral changes and mood disorders, while gut inflammation has been tied to poor systemic health and cardiac inflammation to development of heart disease.

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Section: Discussionmentioning

confidence: 88%

Section: Chronic Juul Inhalation By Inhaled Lps Challenge Does Not Alter Protein Markers Of the Gastrointestinal Tractmentioning

confidence: 99%

Effect of chronic JUUL aerosol inhalation on inflammatory states of the brain, lung, heart and colon in mice

Moshensky

Brand

Alhaddad³

et al. 2021

Preprint

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“…It delivers nicotine by heating a vape liquid containing nicotine, flavoring agents, and different solvents into an aerosol [133]. The aerosol contains different harmful components including (but not limited) flavoring agents, humectants (such as glycerin and propylene glycol), contaminants (such as heavy metals), and harmful solvent byproducts (including formaldehyde and acrolein) in addition to tobacco specific nitrosamines [133,134]. All these substances can harm the cerebrovascular systems and the BBB in a way not too dissimilar from TS [133,134].…”

Section: Vaping (E-cigarette) Covid-19 and Cerebrovascular-neurologmentioning

confidence: 99%

“…The aerosol contains different harmful components including (but not limited) flavoring agents, humectants (such as glycerin and propylene glycol), contaminants (such as heavy metals), and harmful solvent byproducts (including formaldehyde and acrolein) in addition to tobacco specific nitrosamines [133,134]. All these substances can harm the cerebrovascular systems and the BBB in a way not too dissimilar from TS [133,134]. In fact, Kaisar et al recently reported that chronic e-cigarette smoking is responsible for disrupting the BBB integrity and promote vascular inflammation.…”

Section: Vaping (E-cigarette) Covid-19 and Cerebrovascular-neurologmentioning

confidence: 99%

Cerebrovascular and Neurological Dysfunction under the Threat of COVID-19: Is There a Comorbid Role for Smoking and Vaping?

Cucullo

2020

IJMS

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The recently discovered novel coronavirus, SARS-CoV-2 (COVID-19 virus), has brought the whole world to standstill with critical challenges, affecting both health and economic sectors worldwide. Although initially, this pandemic was associated with causing severe pulmonary and respiratory disorders, recent case studies reported the association of cerebrovascular-neurological dysfunction in COVID-19 patients, which is also life-threatening. Several SARS-CoV-2 positive case studies have been reported where there are mild or no symptoms of this virus. However, a selection of patients are suffering from large artery ischemic strokes. Although the pathophysiology of the SARS-CoV-2 virus affecting the cerebrovascular system has not been elucidated yet, researchers have identified several pathogenic mechanisms, including a role for the ACE2 receptor. Therefore, it is extremely crucial to identify the risk factors related to the progression and adverse outcome of cerebrovascular-neurological dysfunction in COVID-19 patients. Since many articles have reported the effect of smoking (tobacco and cannabis) and vaping in cerebrovascular and neurological systems, and considering that smokers are more prone to viral and bacterial infection compared to non-smokers, it is high time to explore the probable correlation of smoking in COVID-19 patients. Herein, we have reviewed the possible role of smoking and vaping on cerebrovascular and neurological dysfunction in COVID-19 patients, along with potential pathogenic mechanisms associated with it.

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“…In first instance, the design of e-cigarettes as electronic nicotine delivery systems has focused the interest of toxicologists on nicotine and on local effects on the respiratory system, but other endpoints of toxicity are also being discussed (Tzortzi et al 2020); current examples are atherosclerosis (Knura et al 2018) and neuroinflammation (Heldt et al 2020). The presence of a considerable number of toxic substances apart from nicotine in the liquid cartridges and in emissions of e-cigarettes has increasingly raised concern (Rehan et al 2018).…”

mentioning

confidence: 99%

Electronic cigarettes and vaping: toxicological awareness is increasing

Bolt

2020

Arch Toxicol

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Electronic cigarette exposure disrupts blood-brain barrier integrity and promotes neuroinflammation

Cited by 43 publications

References 101 publications

Effect of chronic JUUL aerosol inhalation on inflammatory states of the brain, lung, heart and colon in mice

Effect of chronic JUUL aerosol inhalation on inflammatory states of the brain, lung, heart and colon in mice

Cerebrovascular and Neurological Dysfunction under the Threat of COVID-19: Is There a Comorbid Role for Smoking and Vaping?

Electronic cigarettes and vaping: toxicological awareness is increasing

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