Published in:
Open Access
01-12-2011 | Research
Combination of cyclosporine and erythropoietin improves brain infarct size and neurological function in rats after ischemic stroke
Authors:
Chun-Man Yuen, Cheuk-Kwan Sun, Yu-Chun Lin, Li-Teh Chang, Ying-Hsien Kao, Chia-Hung Yen, Yung-Lung Chen, Tzu-Hsien Tsai, Sarah Chua, Pei-Lin Shao, Steve Leu, Hon-Kan Yip
Published in:
Journal of Translational Medicine
|
Issue 1/2011
Login to get access
Abstract
Background
This study tested the superiority of combined cyclosporine A (CsA)-erythropoietin (EPO) therapy compared with either one in limiting brain infarction area (BIA) and preserving neurological function in rat after ischemic stroke (IS).
Methods
Fifty adult-male SD rats were equally divided into sham control (group 1), IS plus intra-peritoneal physiological saline (at 0.5/24/48 h after IS) (group 2), IS plus CsA (20.0 mg/kg at 0.5/24h, intra-peritoneal) (group 3), IS plus EPO (5,000IU/kg at 0.5/24/48h, subcutaneous) (group 4), combined CsA and EPO (same route and dosage as groups 3 and 4) treatment (group 5) after occlusion of distal left internal carotid artery.
Results
BIA on day 21 after acute IS was higher in group 2 than in other groups and lowest in group 5 (all p < 0.01). The sensorimotor functional test showed higher frequency of left turning in group 2 than in other groups and lowest in group 5 (all p < 0.05). mRNA and protein expressions of apoptotic markers and number of apoptotic nuclei on TUNEL were higher in group 2 than in other groups and lowest in group 1 and 5, whereas the anti-apoptotic markers exhibited an opposite trend (all p < 0.05). The expressions of inflammatory and oxidized protein were higher in group 2 than in other groups and lowest in group 1 and 5, whereas anti-inflammatory markers showed reversed changes in group 1 and other groups (all p < 0.05). The number of aquaporin-4+ and glial fibrillary acid protein+ stained cells were higher in group 2 as compared to other groups and lowest in groups 1 and 5 (all p < 0.01).
Conclusion
combined treatment with CsA and EPO was superior to either one alone in protecting rat brain from ischemic damage after IS.