title: Pathobiology of tobacco smoking and neurovascular disorders: untied strings and alternative products.
abstract: Tobacco smoke (TS) is the leading cause of preventable deaths worldwide. In addition to a host of well characterized diseases including chronic obstructive pulmonary disease, oral and peripheral cancers and cardiovascular complications, epidemiological evidence suggests that chronic smokers are at equal risk to develop neurological and neurovascular complications such as multiple sclerosis, Alzheimer's disease, stroke, vascular dementia and small vessel ischemic disease (SVID). Unfortunately, few direct neurotoxicology studies of tobacco smoking and its pathogenic pathways have been produced so far. A major link between TS and CNS disorders is the blood-brain barrier (BBB). In this review article, we summarize the current understanding of the toxicological impact of TS on BBB physiology and function and major compensatory mechanisms such as nrf2- ARE signaling and anti-inflammatory pathways activated by TS. In the same context, we discuss the controversial role of antioxidant supplementation as a prophylactic and/or therapeutic approach in delaying or decreasing the disease complications in smokers. Further, we cover a number of toxicological studies associated with "reduced exposure" cigarette products including electronic cigarettes. Finally, we provide insights on possible avenues for future research including mechanistic studies using direct inhalation rodent models.
authors.affiliation: Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, School of Pharmacy, 1300 S. Coulter Street, Amarillo, TX, 79106, USA. pooja.naik@ttuhsc.edu.
authors.forename: Pooja
authors.initials: P
authors.lastname: Naik
authors.affiliation: Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, School of Pharmacy, 1300 S. Coulter Street, Amarillo, TX, 79106, USA. luca.cucullo@ttuhsc.edu.|Center for Blood Brain Barrier Research, Texas Tech University Health Sciences Center, Amarillo, TX, 79106, USA. luca.cucullo@ttuhsc.edu.
authors.forename: Luca
authors.initials: L
authors.lastname: Cucullo
mesh_terms: D000818:Animals; D061745:Antioxidant Response Elements; D000975:Antioxidants / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism*; D002561:Cerebrovascular Disorders / Q000378:metabolism*; D066300:Electronic Nicotine Delivery Systems / Q000009:adverse effects; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012907:Smoking / Q000009:adverse effects*; D000074606:Smoking Prevention
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human