Comparative assessment of in vitro BBB tight junction integrity following exposure to cigarette smoke and e-cigarette vapor: a quantitative evaluation of the protective effects of metformin using small-molecular-weight paracellular markers.

Introduction:
This study evaluates the impact of tobacco smoke (TS) and electronic cigarette (EC) extracts on the blood-brain barrier (BBB) integrity, as well as the protective effect of metformin. The study used an in vitro BBB model established with iPSC-derived BMECs monolayers cultured on transwell supports to assess the barrier's integrity using paracellular markers that are metabolically inert, non-toxic at the applied doses, not bound to other molecules, and can be reliably quantifiable.

Key Points:

* The study used sucrose and mannitol as paracellular markers to quantitatively assess the impact of TS and EC on the BBB.
* The study found that TS and EC negatively affect sucrose and mannitol permeability starting after 6 hours and up to 24 hours.
* The loss of barrier integrity was associated with a reduction of TEER values.
* The distribution of ZO-1 was altered, and discontinuation patterns were evident through IF imaging, while claudin-5 expression was significantly decreased by TS and EC.
* The levels of TNF-ɑ, PECaM-1, ICaM-1, and VCaM-1 significantly increased after chronic exposure to tobacco and electronic cigarette smoke.
* Chronic smoking and vaping have been reported to disrupt the antioxidative response system by downregulating the expression and activity of Nrf2.
* Metformin has been shown to reduce stress and inhibit inflammatory responses associated with smoke exposure by upregulating Nrf2 expression.

Main Message:
The study found that TS and EC extracts have a negative impact on the BBB integrity, while metformin can counteract these effects. These findings suggest that metformin could be a viable therapeutic option to offset some of the harmful effects associated with chronic smoking/vaping that can negatively impact the integrity of the BBB and the cerebrovascular system, thus promoting the onset and progression of many neurological disorders.

Kadry h, Noorani B, Bickel U, abbruscato TJ, Cucullo L. Comparative assessment of in vitro BBB tight junction integrity following exposure to cigarette smoke and e-cigarette vapor: a quantitative evaluation of the protective effects of metformin using small-molecular-weight paracellular markers. Fluids and barriers of the CNS. 2021;18(1):28. doi:10.1186/s12987-021-00261-4