Yu Yeon Hee, Kim Gun Woo, Lee Yu Ran, Park Dae-Kyoon, Song Beomjong, Kim Duk-Soo
Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan 31151, Republic of Korea.
Research Supporting Center for Medical Science, College of Medicine, Dong-A, Busan 49201, Republic of Korea.
Biomedicines. 2024 Sep 12;12(9):2077. doi: 10.3390/biomedicines12092077.
Cerebral ischemic stroke is a major cause of death worldwide due to brain cell death resulting from ischemia-reperfusion injury. However, effective treatment approaches for patients with ischemic stroke are still lacking in clinical practice. This study investigated the potential neuroprotective effects of sildenafil, a phosphodiesterase-5 inhibitor, in a gerbil model of global brain ischemia. We investigated the effects of sildenafil on the expression of glial fibrillary acidic protein and aquaporin-4, which are markers related to astrocyte activation and water homeostasis, respectively. Immunofluorescence analysis showed that the number of cells co-expressing these markers, which was elevated in the ischemia-induced group, was significantly reduced in the sildenafil-treated groups. This suggests that sildenafil may have a potential mitigating effect on astrocyte activation induced by ischemia. Additionally, we performed various behavioral tests, including the open-field test, novel object recognition, Barnes maze, Y-maze, and passive avoidance tests, to evaluate sildenafil's effect on cognitive function impaired by ischemia. Overall, the results suggest that sildenafil may serve as a neuroprotective agent, potentially alleviating delayed neuronal cell death and improving cognitive function impaired by ischemia.
由于缺血再灌注损伤导致脑细胞死亡，脑缺血性中风是全球范围内主要的死亡原因。然而，在临床实践中，针对缺血性中风患者仍缺乏有效的治疗方法。本研究在沙土鼠全脑缺血模型中研究了磷酸二酯酶5抑制剂西地那非的潜在神经保护作用。我们研究了西地那非对胶质纤维酸性蛋白和水通道蛋白4表达的影响，这两种蛋白分别是与星形胶质细胞活化和水平衡相关的标志物。免疫荧光分析表明，共表达这些标志物的细胞数量在缺血诱导组中升高，而在西地那非治疗组中显著减少。这表明西地那非可能对缺血诱导的星形胶质细胞活化具有潜在的缓解作用。此外，我们进行了各种行为测试，包括旷场试验、新物体识别、巴恩斯迷宫、Y迷宫和被动回避试验，以评估西地那非对缺血受损认知功能的影响。总体而言，结果表明西地那非可能作为一种神经保护剂，潜在地减轻延迟性神经元细胞死亡并改善缺血受损的认知功能。
