Rezaei Sevda, Babataheri Shabnam, Soraya Hamid
Department of Pharmacology and Toxicology, School of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran.
Metab Brain Dis. 2025 Jun 25;40(6):234. doi: 10.1007/s11011-025-01657-z.
Ivermectin (IVM), the recipient of the 2015 Nobel Prize, is an FDA-approved drug for a variety of parasitic diseases in animals and humans. However, the implications of this compound on neurological disorders remain inadequately elucidated. Recently, our research team has elucidated the neuroprotective properties of ivermectin administered in three doses following cerebral ischemia/reperfusion (IR). The objective of the current investigation is to ascertain whether ivermectin sustains its neuroprotective properties through prolonged administration in models of cerebral IR in rats, as well as to evaluate its impact on the formation of neutrophil extracellular traps (NETs). A rat model of transient global cerebral IR was induced by occluding both carotid arteries for 20 min. Ivermectin (2 mg/kg/day) was administered intraperitoneally one hour after the induction of cerebral ischemia for 7 consecutive days at 24-hour intervals. Then, the effects of ivermectin on brain infarct size, blood cell profile, bleeding time, memory and learning, balance and motor coordination, myeloperoxidase enzyme activity, and H3cit protein levels were investigated. The finding showed that the administration of ivermectin for 7 days did not improve memory and learning, blood parameters, or cerebral infarct size. However, it caused a 25.4% reduction in citrullinated histone protein level, decreased myeloperoxidase activity (P = 0.017), and improved balance and motor coordination (P = 0.017 and P = 0.024). In conclusion, our findings indicate that prolonged administration of ivermectin may diminish its neuroprotective effects and its effects can differ depending on the drug regimen.
伊维菌素（IVM）是2015年诺贝尔奖得主，是一种经美国食品药品监督管理局（FDA）批准用于治疗动物和人类多种寄生虫病的药物。然而，这种化合物对神经系统疾病的影响仍未得到充分阐明。最近，我们的研究团队阐明了脑缺血/再灌注（IR）后给予三种剂量伊维菌素的神经保护特性。本研究的目的是确定伊维菌素在大鼠脑IR模型中通过长期给药是否能维持其神经保护特性，以及评估其对中性粒细胞胞外陷阱（NETs）形成的影响。通过阻断双侧颈动脉20分钟诱导大鼠短暂性全脑IR模型。在脑缺血诱导后1小时，以24小时间隔连续7天腹腔注射伊维菌素（2mg/kg/天）。然后，研究了伊维菌素对脑梗死体积、血细胞谱、出血时间、记忆和学习、平衡和运动协调、髓过氧化物酶活性和H3cit蛋白水平的影响。结果表明，连续7天给予伊维菌素并不能改善记忆和学习、血液参数或脑梗死体积。然而，它使瓜氨酸化组蛋白水平降低了25.4%，髓过氧化物酶活性降低（P = 0.017），并改善了平衡和运动协调（P = 0.017和P = 0.024）。总之，我们的研究结果表明，长期给予伊维菌素可能会减弱其神经保护作用，其效果可能因给药方案而异。
