Exposure to synthetic pyrethroid (SPs) pesticides such as bifenthrin (BF) has been associated with adverse neurodevelopmental outcomes and cognitive impairments, but the underlying neurobiological mechanism is poorly understood so far. The present study has been designed to evaluate changes in behavior and in biomarkers of oxidative stress and neuroinflammation in the hippocampus of rats subchronically treated with BF. Rats exposed daily to BF at doses of 0.6 and 2.1 mg/kg b. w. for 60 days exhibited spatial and cognitive impairments as well as memory dysfunction after 60 days. This repeated BF treatment also significantly increased mRNA expression of pro-inflammatory cytokines tumor necrosis factor (TNF-α), interleukin (IL-1β), (IL-6), nuclear factor erythroid-2 (Nrf2), cyclooxygenase-2 (COX-2), nuclear factor-kappaB pathway (NF-kappaB), and prostaglandin E₂ (PGE₂) in the hippocampus. It further resulted in a significant increase in protein levels of Nrf2, COX-2, microsomal prostaglandin synthase-1 (mPGES-1) and NF-kappaB. This was accompanied by oxidative/nitrosative stress in the hippocampus of treated rats, as shown by increased levels of malondialdehyde (MDA), protein carbonyls (PCO), and nitric oxide (NO), and reduced levels of enzymatic (catalase, superoxide dismutase, and glutathione peroxidase) and non-enzymatic (reduced glutathione) antioxidants. The data are in line with those obtained in organotypic hippocampal slice cultures (OHSCs) isolated from mouse brain and exposed to BF for 72 h, showing neuronal death only at the high dose of 20 μM when compared to controls.

These findings suggest that exposure to BF induces neuronal damage, alters redox state, and causes neuroinflammation in the hippocampus, which might lead to cognitive and memory impairment.

接触合成的拟除虫菊酯（SPs）杀虫剂（如联苯菊酯（BF））与不良的神经发育结果和认知障碍有关，但到目前为止，对潜在的神经生物学机制了解甚少。本研究的目的是评估用BF长期治疗的大鼠海马的行为以及氧化应激和神经炎症的生物标志物的变化。每天以0.6和2.1 mg / kg bw的剂量暴露于BF达60天的大鼠在60天后表现出空间和认知障碍以及记忆功能障碍。这种反复的BF处理还显着增加了促炎性细胞因子肿瘤坏死因子（TNF-α），白介素（IL-1β），（IL-6），核因子红系-2（Nrf2），环氧合酶2（COX）的mRNA表达-2），核因子-kappaB通路（NF-kappaB），₂（PGE ₂）在海马中。它进一步导致Nrf2，COX-2，微粒体前列腺素合酶1（mPGES-1）和NF-κB的蛋白质水平显着增加。这伴随着被治疗大鼠海马的氧化/亚硝化应激，如丙二醛（MDA），蛋白羰基（PCO）和一氧化氮（NO）的水平升高以及酶促（过氧化氢酶，超氧化物歧化酶，和谷胱甘肽过氧化物酶）和非酶类（还原型谷胱甘肽）抗氧化剂。数据与从小鼠脑分离并暴露于BF的器官型海马切片培养物（OHSC）中获得的数据一致，与对照组相比，仅在20μM高剂量下显示神经元死亡。

这些发现表明，暴露于BF会引起神经元损伤，改变氧化还原状态，并引起海马神经发炎，这可能导致认知和记忆障碍。