Journal
TOXICOLOGY LETTERS
Volume 214, Issue 2, Pages 120-130Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2012.08.021
Keywords
NO2; Ischemic stroke; Endothelial dysfunction; Inflammation
Categories
Funding
- National Natural Science Foundation of PR China [20877050, 21007036, 21222701]
- Specialized Research Fund for the Doctoral Program of Higher Education (SRFDP) [20091401110002]
- Program for New Century Excellent Talents in University (NCET) [NCET-10-0927]
- Natural Science Foundation of Shanxi Province [2012021008-1]
- Shanxi Scholarship Council of China [2011-013, 2012-009]
- Program for the Top Young and Middleaged Innovative Talents of Higher Learning Institutions of Shanxi (TYMIT)
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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/m(3) 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. (c) 2012 Elsevier Ireland Ltd. All rights reserved.
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