Chitkara College of Pharmacy, Chitkara University, Punjab, 140401, India.
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, 147002, India.
Neurochem Res. 2022 Aug;47(8):2230-2243. doi: 10.1007/s11064-022-03609-w. Epub 2022 Apr 28.
Various studies have evidenced the neuroprotective role of PDE4 inhibitors. However, whether PDE4 inhibitor, Piclamilast pharmacological post-treatment is protective during cerebral ischemia reperfusion-induced injury remains unknown. Therefore, this study design included testing the hypothesis that Piclamilast administered at the beginning of a reperfusion phase (Piclamilast pPost-trt) shows protective effects and explores & probes underlying downstream mechanisms. Swiss albino male mice were subjected to global ischemic and reperfusion injury for 17 min. The animals examined cerebral infarct size, biochemical parameters, inflammatory mediators, and motor coordination. For memory, assessment mice were subjected to morris water maze (MWM) and elevated plus maze (EPM) test. Histological changes were assessed using HE staining. Piclamilast pPost-trt significantly reduced I/R injury-induced deleterious effects on biochemical parameters of oxidative stress, inflammatory parameters, infarct size, and histopathological changes, according to the findings. These neuroprotective effects of pPost-trt are significantly abolished by pre-treatment with selective CREB inhibitor, 666-15. Current study concluded that induced neuroprotective benefits of Piclamilast Post-trt, in all probability, maybe mediated through CREB activation. Hence, its neuroprotective effects can be further explored in clinical settings.
多项研究证实了 PDE4 抑制剂的神经保护作用。然而,PDE4 抑制剂皮拉米司特在脑缺血再灌注损伤诱导的损伤中,药物治疗后是否具有保护作用尚不清楚。因此,本研究设计包括检验以下假设:在再灌注期开始给予皮拉米司特(皮拉米司特 pPost-trt)具有保护作用,并探索和探测潜在的下游机制。将瑞士白化雄性小鼠进行全脑缺血再灌注损伤 17 分钟。检查动物的脑梗死面积、生化参数、炎症介质和运动协调能力。为了评估记忆,将小鼠进行 Morris 水迷宫(MWM)和高架十字迷宫(EPM)测试。使用 HE 染色评估组织学变化。研究结果表明,皮拉米司特 pPost-trt 显著减轻了 I/R 损伤诱导的生化参数(氧化应激、炎症参数、梗死面积和组织病理学变化)的有害影响。pPost-trt 的这些神经保护作用被选择性 CREB 抑制剂 666-15 的预处理显著消除。本研究得出结论,皮拉米司特 pPost-trt 诱导的神经保护益处可能是通过 CREB 激活介导的。因此,其神经保护作用可以在临床环境中进一步探索。