Exploring and repurposing a drug have become a lower risk alternative. Safinamide, approved for Parkinson’s disease, has shown neuroprotection in various animal models of neurological disorders. The present study aimed to explore the potential of safinamide in cerebral ischemia/reperfusion (I/R) in rats. Sprague–Dawley rats were used in middle cerebral artery occlusion model of stroke. The effective dose of safinamide was selected based on the results of neurobehavioral parameters and reduction in infarct size assessed 24 h post-reperfusion. For sub-acute study, the treatment with effective dose was extended for 3 days and effects on neurobehavioral parameters, infarct size (TTC staining and MRI), oxidative stress parameters (MDA, GSH, SOD, NOX-2), inflammatory cytokines (TNF-α, IL-1β, IL-10), apoptosis (Bax, Bcl-2, cleaved caspase-3 expression, and TUNEL staining), and autophagy (pAMPK, Beclin-1, LC3-II expression) were studied. The results of dose selection study showed significant reduction (p < 0.05) in infarct size and improvement in neurobehavioral parameters with safinamide (80 mg/kg). In sub-acute study, safinamide showed significant (p < 0.05) improvement in motor coordination and infarct size reduction. Additionally, safinamide treatment significantly normalized altered redox homeostasis and inflammatory cytokine levels. However, no change was observed in expression of NOX-2 in I/R or safinamide treatment group when compared with sham. I/R induced deranged expression of apoptotic markers and increased TUNEL positive cells in cortex were significantly normalized with safinamide treatment. Further, safinamide significantly (p < 0.05) induced the expressions of autophagic proteins (Beclin-1 and LC3-II) in cortex. Overall, the results demonstrated neuroprotective potential of safinamide via anti-oxidant, anti-inflammatory, anti-apoptotic, and autophagy inducing properties. Thus, safinamide can be explored for repurposing in ischemic stroke after further exploration.

探索和重新利用药物已成为风险较低的选择。Safinamide 被批准用于帕金森病，已在各种神经疾病动物模型中显示出神经保护作用。本研究旨在探讨 safinamide 在大鼠脑缺血/再灌注 (I/R) 中的潜力。Sprague-Dawley 大鼠用于脑中动脉闭塞模型。根据神经行为参数的结果和再灌注后 24 小时评估的梗塞面积减少情况选择沙非酰胺的有效剂量。对于亚急性研究，有效剂量治疗延长 3 天，并影响神经行为参数、梗死面积（TTC 染色和 MRI）、氧化应激参数（MDA、GSH、SOD、NOX-2）、炎性细胞因子（TNF -α, IL-1β, IL-10), 细胞凋亡 (Bax, Bcl-2, cleaved caspase-3 表达, 和 TUNEL 染色）和自噬（pAMPK、Beclin-1、LC3-II 表达）进行了研究。剂量选择研究结果显示显着降低（p  < 0.05) 用 safinamide (80 mg/kg) 改善梗死面积和改善神经行为参数。在亚急性研究中，safinamide 在运动协调和梗塞面积缩小方面显示出显着 ( p < 0.05) 的改善。此外，safinamide 治疗显着使改变的氧化还原稳态和炎性细胞因子水平正常化。然而，与假手术相比，I/R 或 safinamide 治疗组中 NOX-2 的表达没有观察到变化。I/R 诱导的凋亡标志物的异常表达和皮质中增加的 TUNEL 阳性细胞在用 safinamide 处理后显着正常化。此外，safinamide显着（p < 0.05) 诱导皮质中自噬蛋白 (Beclin-1 和 LC3-II) 的表达。总体而言，结果证明了safinamide通过抗氧化、抗炎、抗凋亡和自噬诱导特性的神经保护潜力。因此，在进一步探索后，可以探索safinamide用于缺血性卒中的再利用。