Aniol Victor A, Lazareva Natalia A, Moiseeva Yulia V, Nedogreeva Olga A, Novikova Margarita R, Kostryukov Pavel A, Onufriev Mikhail V, Gulyaeva Natalia V
Laboratory of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 117485 Moscow, Russia.
Research and Clinical Center for Neuropsychiatry of Moscow Healthcare Department, 115419 Moscow, Russia.
Int J Mol Sci. 2025 Jun 13;26(12):5668. doi: 10.3390/ijms26125668.
Oxidative stress and membrane damage are believed to be principally involved in the pathogenesis of epilepsy. This study aimed to assess the effects of phenosanic acid (PA), an antioxidant and membrane protector, in acute pentylenetetrazole and chronic lithium-pilocarpine seizure models in male Wistar rats. PA was administered acutely (ip, 120 mg/kg BW ip, or 240 mg/kg BW per os) or chronically (80 mg/kg BW/day per os). Indices of free radical oxidation, the hypothalamo-pituitary-adrenocortical axis, and the nitrergic system were assessed in blood and brain regions. Morphological analysis of the hippocampus was performed in the lithium-pilocarpine model. PA exerted an acute anti-seizure effect in the pentylenetetrazole model. In the lithium-pilocarpine model, acute PA treatment decreased the death rate and corticosterone levels in the neocortex and brainstem. In contrast, the level of free radical oxidation products reacting with thiobarbituric acid declined in the brain stem in response to chronic PA treatment. In the lithium-pilocarpine model, the neuronal density in the dentate gyrus was elevated, and the proliferating cell nuclear antigen positive (PCNA+) cell counts in the subgranular zone did not differ between groups. Doublecortin positive (DCX+) cell count was significantly increased after chronic PA treatment. PA-induced reduction in mortality in the lithium-pilocarpine epilepsy model may be partially mediated by decreasing the lipid peroxidation and corticosterone levels in different brain regions. Chronic PA treatment may affect adult hippocampal neurogenesis by either prolonging the action of factors that increase neurogenesis after status epilepticus or by slowing down the neuronal differentiation rate. These data suggest that PA may be a disease-modifying AED able to hamper epileptogenesis.
氧化应激和膜损伤被认为主要参与癫痫的发病机制。本研究旨在评估抗氧化剂和膜保护剂苯磺酸（PA）对雄性Wistar大鼠急性戊四氮和慢性锂-匹罗卡品癫痫模型的影响。PA通过急性（腹腔注射，120mg/kg体重腹腔注射，或口服240mg/kg体重）或慢性（口服80mg/kg体重/天）给药。评估血液和脑区中自由基氧化、下丘脑-垂体-肾上腺皮质轴和氮能系统的指标。在锂-匹罗卡品模型中对海马进行形态学分析。PA在戊四氮模型中发挥急性抗癫痫作用。在锂-匹罗卡品模型中，急性PA治疗降低了新皮层和脑干的死亡率和皮质酮水平。相反，慢性PA治疗后，脑干中与硫代巴比妥酸反应的自由基氧化产物水平下降。在锂-匹罗卡品模型中，齿状回的神经元密度升高，颗粒下区增殖细胞核抗原阳性（PCNA+）细胞计数在各组之间无差异。慢性PA治疗后双皮质素阳性（DCX+）细胞计数显著增加。PA诱导锂-匹罗卡品癫痫模型死亡率降低可能部分是通过降低不同脑区的脂质过氧化和皮质酮水平介导的。慢性PA治疗可能通过延长癫痫持续状态后增加神经发生的因子的作用或通过减缓神经元分化速率来影响成年海马神经发生。这些数据表明PA可能是一种能够阻碍癫痫发生的疾病修饰性抗癫痫药物。
