Abstract
Objectives: This study tested the superiority of combined cyclosporine (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 0.5/24/48h 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 treatment (group 5) after occlusion of distal left internal carotid artery. Results: BIA on day 21 after acute IS was highest in group 2 and lowest in group 5 (all p<0.01). The sensorimotor functional test showed highest frequency of left turning in group 2 and lowest in group 5 (all p<0.05). mRNA and protein expressions of apoptotic markers and number of apoptotic nuclei on TUNEL were highest in group 2 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 highest in group 2 and lowest in group 1 and 5, whereas anti-inflammatory markers showed reversed changes in group 1 and 5 (all p<0.05). The number of aquaporin - 4+ and glial fibrillary acid protein+ stained cells were highest in group 2 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 (the proposed mechanisms of potential therapeutic impact of combined therapy with CsA and EPO on acute IS have been summarized in the figure)
Published Version
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