To evaluate the ameliorating effect of Modafinil on neuroinflammation, behavioral, and histopathological alterations in rats induced by propionic acid (PPA). Thirty male Wistar rats were used in the study, divided into 3 groups of ten subjects. One group served as a control, the subjects in the other two were given 250 mg/kg/day of PPA by intraperitoneal injection over the course of 5 days to induce autism. The experimental design was as follows: Group 1: Normal control (orally-fed control, n = 10); Group 2 (PPA + saline, n = 10): PPA and 1 ml/kg/day % 0.9 NaCl saline via oral gavage; Group 3 (PPA + Modafinil, n = 10) PPA and 30 mg/kg/day Modafinil (Modiodal tablets 100 mg, Cephalon) via oral gavage. All of the groups were investigated for behavioral, biochemical, and histological abnormality. Autism-like behaviors were reduced significantly in the rats treated with PPA. TNF-α, Nerve Growth Factor (NGF), IL-17, IL-2, and NF-KB levels as well as MDA levels and lactate were significantly higher in those treated with PPA compared to the control group. Using immunohistochemical methods, the number of neurons and GFAP immunoreactivity was significantly altered in PPA-treated rats compared to the control. Using Magnetic Resonance Spectroscopy (MRS), we found that lactate levels were significantly higher in the PPA-treated rats, while creatinine levels were significantly decreased. In the rats administered with Modafinil, behavior, neuroinflammation, and histopathological changes brought about by PPA were significantly reversed. Our results demonstrate the potential role of Modafinil in ameliorating PPA-induced neuroinflammation in rats.

Graphical Abstract

中文翻译：

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莫达非尼通过减少神经炎症来改善大鼠的自闭症样行为

评价莫达非尼对丙酸（PPA）诱导的大鼠神经炎症、行为和组织病理学改变的改善作用。该研究使用了 30 只雄性 Wistar 大鼠，分为 3 组，每组 10 名受试者。一组作为对照，另外两组受试者在 5 天的时间内通过腹腔注射 250 毫克/公斤/天的 PPA 来诱导自闭症。实验设计如下：第1组：正常对照（口服喂养对照，n=10）；第 2 组（PPA + 盐水，n = 10）：通过口服管饲法添加 PPA 和 1 ml/kg/天 % 0.9 NaCl 盐水；第 3 组（PPA + 莫达非尼，n = 10）通过口服管饲法给予 PPA 和 30 mg/kg/天莫达非尼（Modiodal 片剂 100 mg，Cephalon）。对所有组的行为、生化和组织学异常进行了调查。使用 PPA 治疗的大鼠的自闭症样行为显着减少。与对照组相比，PPA 治疗组的 TNF-α、神经生长因子 (NGF)、IL-17、IL-2 和 NF-KB 水平以及 MDA 水平和乳酸显着升高。使用免疫组织化学方法，与对照组相比，PPA 治疗的大鼠的神经元数量和 GFAP 免疫反应性显着改变。使用磁共振波谱 (MRS)，我们发现 PPA 治疗的大鼠的乳酸水平显着升高，而肌酐水平显着降低。在给予莫达非尼的大鼠中，PPA引起的行为、神经炎症和组织病理学变化均得到显着逆转。我们的结果证明了莫达非尼在改善大鼠 PPA 诱导的神经炎症中的潜在作用。

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