Hashemi Paria, Mardani Parastoo, Eghbali Raz Zabihollah, Saedi Ali, Fatahi Ehsan, Izapanah Esmael, Ahmadi Shamseddin
Department of Biological Science, Faculty of Science, University of Kurdistan, P.O. Box 416, Sanandaj, Iran.
Department of Biology, Payame Noor University, Tehran, Iran.
Mol Neurobiol. 2025 Feb;62(2):2264-2276. doi: 10.1007/s12035-024-04407-x. Epub 2024 Aug 3.
The development and progression of temporal lobe epilepsy (TLE) are heavily influenced by inflammation, excessive activation of glial cells, and neuronal cell death. This study aimed to investigate the effects of treatment with alpha-pinene (APN) on pro-and anti-inflammatory cytokine levels, astrogliosis, pyroptosis, and autophagy markers in the hippocampus in a rat model of TLE induced by kainic acid (KA). Male Wistar rats were employed, and TLE was induced by intracerebroventricular injection of KA. APN (50 mg/kg) was intraperitoneally administered for 19 days, including two weeks before and five days after the administration of KA. After full recovery from anesthesia and KA injection, the seizure-related behavioral expressions were evaluated. On day 19, the hippocampal levels of IL-1β, TNF-α, progranulin, IL-10, ERK1/2, phospho-ERK1/2, NF-κB, GFAP, S100-B, NLRP1, NLRP3, caspase-1, and becline-1 were examined. The results revealed that treatment with APN significantly diminished the heightened levels of IL-1β, TNF-α, progranulin, ERK1/2, and NF-κB and reversed the reduced levels of the anti-inflammatory cytokine, IL-10, in the hippocampus caused by KA. Furthermore, administration of APN significantly reduced the levels of astrogliosis, pyroptosis, and autophagy markers in the hippocampus that were elevated by KA. It can be concluded that treatment with APN for 19 days alleviated neuroinflammation by inhibiting ERK1/2 and NF-κB signaling pathways and prevented increases in astrogliosis, pyroptosis, and autophagy markers in the hippocampus in a rat model of TLE.
颞叶癫痫(TLE)的发生和进展受到炎症、胶质细胞过度激活以及神经元细胞死亡的严重影响。本研究旨在探讨α-蒎烯(APN)治疗对 kainic 酸(KA)诱导的 TLE 大鼠模型海马中促炎和抗炎细胞因子水平、星形胶质细胞增生、细胞焦亡及自噬标志物的影响。采用雄性 Wistar 大鼠,通过脑室内注射 KA 诱导 TLE。APN(50mg/kg)腹腔注射 19 天,包括在注射 KA 前两周和注射后五天。在从麻醉和 KA 注射中完全恢复后,评估癫痫相关的行为表现。在第 19 天,检测海马中白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、颗粒蛋白前体、白细胞介素-10(IL-10)、细胞外信号调节激酶 1/2(ERK1/2)、磷酸化 ERK1/2、核因子-κB(NF-κB)、胶质纤维酸性蛋白(GFAP)、S100B 蛋白、NLRP1、NLRP3、半胱天冬酶-1(caspase-1)和贝克林-1(becline-1)的水平。结果显示,APN 治疗显著降低了 KA 引起的海马中 IL-1β、TNF-α、颗粒蛋白前体、ERK1/2 和 NF-κB 的升高水平,并逆转了抗炎细胞因子 IL-10 的降低水平。此外,APN 给药显著降低了 KA 升高的海马中星形胶质细胞增生、细胞焦亡及自噬标志物的水平。可以得出结论,在 TLE 大鼠模型中,APN 治疗 19 天通过抑制 ERK