Department of Physiology, Bolu Abant Izzet Baysal University, Bolu, Turkey.
Department of Physiology, Istanbul Health and Technology University, Istanbul, Turkey.
Eur J Neurosci. 2022 May;55(9-10):2912-2924. doi: 10.1111/ejn.15145. Epub 2021 Feb 23.
Neuroinflammation plays a key role in the pathogenesis of epilepsy, but the underlying mechanisms are not well understood. Mast cells are multifunctional immune cells that are also activated by stress. The effects of activated mast cells on epileptogenesis are not yet known. This study investigated the effects and mechanisms of compound 48/80-stimulated mast cell activation on pentylenetetrazole-induced epileptic seizures in rats. Male Wistar rats were separated into seven groups (n = 12). Group-1(NS+PTZ) received intraperitoneal saline solution, while groups 2(C-48/80+PTZ-1), 3(C-48/80+PTZ-2), and 4(C-48/80+PTZ-3) received compound-48/80 at doses of 0.5, 1, and 2 mg/kg, respectively, 30 min before 45 mg/kg pentylenetetrazole administration. Similarly, Group-5(Cr+C-48/80+PTZ) received 10 mg/kg cromolyn plus 2 mg/kg compound-48/80 before pentylenetetrazole, and Group-6(MC Dep+C-48/80+PTZ) was exposed to a mast cell-depletion process, and then received 2 mg/kg compound-48/80. Group-7(5-HT+PTZ) received 10 mg/kg serotonin. Seizure stages were evaluated using Racine's scale. Compound-48/80 at 2 mg/kg induced anticonvulsive effects against pentylenetetrazole-induced seizures by extending onset-times of both myoclonic-jerk and generalized tonic-clonic seizures (p = 0.0001), and by shortening the duration of generalized tonic-clonic seizure (p = 0.008). These effects were reversed by cromolyn (p = 0.0001). These effects were not observed in mast cell-depleted rats. Similarly to compound 48/80, serotonin also exhibited anticonvulsive effects against seizures (p < 0.05). Compound 48/80 acts as an anticonvulsant by activating mast cells in a dose-dependent manner. The anticonvulsive effects of mast cell activation may be mediated by serotonin. Mast cell activation may therefore provide protective activity against seizures under appropriate circumstances.
神经炎症在癫痫的发病机制中起关键作用，但其中的潜在机制尚不清楚。肥大细胞是多功能免疫细胞，也可被应激激活。目前尚不清楚激活的肥大细胞对癫痫发生的影响。本研究旨在探讨化合物 48/80 刺激肥大细胞激活对戊四氮诱导的大鼠癫痫发作的影响及其机制。雄性 Wistar 大鼠被分为 7 组（n=12）。第 1 组（NS+PTZ）腹腔注射生理盐水，第 2 组（C-48/80+PTZ-1）、第 3 组（C-48/80+PTZ-2）及第 4 组（C-48/80+PTZ-3）分别于戊四氮前 30 分钟腹腔注射 0.5、1、2 mg/kg 的化合物 48/80，第 5 组（Cr+C-48/80+PTZ）于戊四氮前接受 10 mg/kg 色甘酸钠加 2 mg/kg 化合物 48/80，第 6 组（MC Dep+C-48/80+PTZ）行肥大细胞耗竭处理，然后腹腔注射 2 mg/kg 化合物 48/80，第 7 组（5-HT+PTZ）腹腔注射 10 mg/kg 5-羟色胺。采用 Racine 量表评估癫痫发作阶段。2 mg/kg 化合物 48/80可通过延长戊四氮引起的肌阵挛性抽搐和全面强直阵挛性发作的发作时间（p=0.0001）和缩短全面强直阵挛性发作持续时间（p=0.008）来对抗戊四氮引起的癫痫发作，这些作用可被色甘酸钠逆转（p=0.0001）。在肥大细胞耗竭大鼠中未观察到这些作用。与化合物 48/80 相似，5-羟色胺也对癫痫发作具有抗惊厥作用（p<0.05）。化合物 48/80 通过剂量依赖性方式激活肥大细胞发挥抗惊厥作用。肥大细胞激活的抗惊厥作用可能通过 5-羟色胺介导。因此，在适当的情况下，肥大细胞激活可能提供对癫痫发作的保护作用。
