Fig. 1

Schematic representation of the brain microvasculature features and corresponding Impact of TS: a Schematic illustration of a cross sectional view of a brain capillary. Note the endothelial cells are surrounded by supporting astrocytic end feet processes and pericytes along with the ensheathing basal lamina. b Paracellular passage of substances across the BBB endothelial layer is restricted by junctional protein complexes consisting of TJ proteins (such as occludin, claudins, JAMs); along with adherens junction protein VE-cadherin and catenins. Note that the cytoplasmic accessory protein ZO-1 intercalates these intercellular proteins with the cytoskeleton. c TS-produced ROS promotes oxidative stress responses at the BBB endothelium. These include the activation of several transcription factors including Nf-κB and the antioxidant response system via nrf2-ARE pathway. This latter in turn activates anti-oxidant and detoxification genes. The downstream effect of TS exposure leads to the down regulation of TJ proteins; increase in vascular permeability and activation of pro-inflammatory responses leading to BBB dysfunction