Environmental nitrogen dioxide (NO2) exposure influences development and progression of ischemic stroke

Here the correlativity between NO2, a representative pollutant of vehicle exhaust, and ischemic stroke was first determined under experimental conditions following some epidemiological reports. First, we found that blood viscosity, red blood cell (RBC) aggregation-, electrophoresis- and rigidity-index in healthy rats were increased after exposure to 5 mg/m3 NO2 for one- and three-month. Based on this, we set up stroke rat model and exposed them to NO2 at the same concentration for one week, and found that NO2 exposure time-dependently delayed neurological structure and function recovery of MCAO (middle cerebral artery occlusion) rat, and worsened pathological injuries and apoptosis induced by MCAO operation. Endothelial and inflammatory responses, two common cellular pathomechanisms involved in ischemic brain damage, were induced in cortex by MCAO treatment and exacerbated by followed NO2 inhalation. Expression of the endothelial and inflammatory biomarkers in stroke displayed the same tendency in healthy rats after sub-acute and sub-chronic NO2 exposure as in MCAO model in a concentration-dependent manner. Our data provide evidence that environmental NO2 is an important inducer, and also a promoter of ischemic stroke, with endothelial nitric oxide synthase (eNOS), cyclooxygenase-2 (COX-2) and intercellular adhesion molecule 1 (ICAM-1) being potential indicators of this effect.

► Environmental NO2 exposure increases the risk of ischemic stroke. ► Environmental NO2 exposure worsens the outcome of ischemic stroke. ► eNOS, COX-2 and ICAM-1 are potential biomarkers in NO2 induced ischemic stroke.