Hussein Hussein Allawi, Moghimi Ali, Roohbakhsh Ali
Rayan Center for Neuroscience and Behavior, Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Iran.
Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
Iran J Basic Med Sci. 2019 Mar;22(3):267-276. doi: 10.22038/ijbms.2019.35056.8339.
Pioglitazone (PGZ), a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist, has significant neuroprotective effects and has been reported to regulate inflammatory processes.
We evaluated the effects of PGZ on febrile seizure (FS) in rat pups. Three groups of male rat pups received intraperitoneal (IP) injections of PGZ (5, 10, and 20 mg/kg). Lipopolysaccharide (LPS) and kainic acid (KA) were injected to induce FS. The rat pups behaviors were recorded and analyzed. Seizure latency, duration, and severity were recorded to evaluate the effect of PGZ on FS. Novel object recognition task (NORT) was used to evaluate the effect of PGZ on cognitive deficits induced by FS. At the end of the experimental protocol, molecular and histological tests were done.
PGZ significantly increased seizure latency and decreased seizure duration and median of seizure scores (<0.05, <0.01, and <0.001) after induction of FS. Rat pups exposed to FS had memory deficits both in short-term and long-term memories in the NORT that were reversed by PGZ-treatment (<0.01 and <0.001). PGZ significantly reduced interleukin-1β, tumor necrosis factor-α, and inducible nitric oxide synthase concentration in the hippocampus (<0.05 and <0.01). In addition, PGZ decreased the number of degenerating and TUNEL positive neurons in CA1, CA3, and DG subfields of the hippocampus (<0.05, <0.01 and <0.001).
The present results indicated that PGZ had anticonvulsant, anti-inflammatory, and anti-apoptotic effects with ameliorative effects on cognitive deficits induced by FS in rat pups.
吡格列酮（PGZ）是一种过氧化物酶体增殖物激活受体γ（PPAR-γ）激动剂，具有显著的神经保护作用，据报道可调节炎症过程。
我们评估了PGZ对幼鼠热性惊厥（FS）的影响。三组雄性幼鼠接受腹腔注射PGZ（5、10和20mg/kg）。注射脂多糖（LPS）和 kainic 酸（KA）以诱导FS。记录并分析幼鼠的行为。记录惊厥潜伏期、持续时间和严重程度，以评估PGZ对FS的影响。采用新物体识别任务（NORT）评估PGZ对FS诱导的认知缺陷的影响。在实验方案结束时，进行分子和组织学检测。
诱导FS后，PGZ显著延长惊厥潜伏期，缩短惊厥持续时间，并降低惊厥评分中位数（<0.05、<0.01和<0.001）。暴露于FS的幼鼠在NORT中的短期和长期记忆均存在记忆缺陷，PGZ治疗可逆转这些缺陷（<0.01和<0.001）。PGZ显著降低海马中白细胞介素-1β、肿瘤坏死因子-α和诱导型一氧化氮合酶的浓度（<0.05和<0.01）。此外，PGZ减少了海马CA1、CA3和DG亚区中变性和TUNEL阳性神经元的数量（<0.05、<0.01和<0.001）。
目前的结果表明，PGZ具有抗惊厥、抗炎和抗凋亡作用，对幼鼠FS诱导的认知缺陷具有改善作用。
