E-cigarettes have gained popularity as alternatives to traditional cigarettes, yet their neurological safety profile remains insufficiently understood. To evaluate current evidence on the neurophysiological effects of e-cigarette inhalation, with focus on blood–brain barrier (BBB) integrity, glucose transport, stroke risk, and cognitive outcomes, in comparison to cigarette smoking. A narrative literature review of animal, cellular, and human studies published between 2000 and 2025 was conducted using PubMed, Embase, and Scopus. The review focused on research exploring how e-cigarette or nicotine aerosol exposure affects the blood-brain barrier (BBB), glucose transporter expression, neuroinflammation, ischemic injury, and cognitive function. Comparative cigarette data were incorporated. Across 20 + studies, e-cigarette exposure consistently downregulated BBB tight junction proteins (ZO-1, claudin-3) and increased permeability, oxidative stress, and inflammatory markers (PECAM-1, ICAM-1, VCAM-1, TNF-α). At least six studies demonstrated reduced GLUT1 and GLUT3 expression and impaired cerebral glucose transport, particularly under ischemic conditions, resulting in exacerbated stroke severity. Five animal studies reported cognitive impairments, including memory loss and reduced spatial processing, along with elevated cortical TNF-α. Metformin was shown in three preclinical studies to attenuate BBB dysfunction and inflammation, suggesting potential therapeutic benefit. Current evidence indicates that e-cigarettes are not neurologically inert. Their effects on barrier integrity, metabolic transport, and inflammatory pathways parallel many of the harms established for cigarette smoke, raising concerns about increased susceptibility to stroke and cognitive decline. Despite lower exposure to some combustion products, e-cigarettes do not appear neurologically benign. Further long-term clinical studies are urgently needed.
Al-Bana et al. (Tue,) studied this question.
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