Mast cell activation ameliorates pentylenetetrazole-induced seizures in rats: The potential role for serotonin
Mast cell activation ameliorates pentylenetetrazole-induced seizures in rats: The potential role for serotonin
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DOI：
10.1111/ejn.15145
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发表时间：
2021-02-23
影响因子：
3.4
通讯作者：
Tore, Fatma
中科院分区：
文献类型：
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作者：
Kilinc, Erkan;Torun, Ibrahim Ethem;Tore, Fatma
神经炎症在癫痫的发病机制中起着关键作用，但其潜在机制尚不清楚。肥大细胞是多功能免疫细胞，也会被压力激活。激活的肥大细胞对癫痫发生的影响尚不清楚。本研究探讨了化合物 48/80 刺激的肥大细胞激活对戊四唑诱导的大鼠癫痫发作的影响和机制。雄性 Wistar 大鼠被分为七组（n = 12）。第1组(NS+PTZ)接受腹腔内盐水溶液，而第2组(C-48/80+PTZ-1)、第3组(C-48/80+PTZ-2)和第4组(C-48/80+PTZ-3)分别在45mg/kg前30分钟接受剂量为0.5、1和2mg/kg的化合物-48/80戊四唑给药。类似地，组5（Cr+C-48/80+PTZ）在戊四唑之前接受10mg/kg色甘酸加2mg/kg化合物48/80，组6（MC Dep+C-48/80+PTZ）暴露于肥大细胞耗竭过程，然后接受2mg/kg化合物48/80。第 7 组（5-HT+PTZ）接受 10 mg/kg 血清素。使用拉辛量表评估癫痫发作阶段。 2 mg/kg 的化合物 48/80 通过延长肌阵挛性抽搐和全身强直阵挛发作的发作时间（p = 0.0001），并通过缩短全身强直阵挛发作的持续时间（p = 0.008），诱导针对戊四唑诱导的癫痫发作的抗惊厥作用。色甘酸可逆转这些效应 (p = 0.0001)。在肥大细胞耗尽的大鼠中没有观察到这些效应。与化合物 48/80 类似，血清素也表现出抗癫痫发作的抗惊厥作用 (p < 0.05)。化合物 48/80 通过以剂量依赖性方式激活肥大细胞而起到抗惊厥药的作用。肥大细胞激活的抗惊厥作用可能是由血清素介导的。因此，在适当的情况下，肥大细胞的激活可以提供针对癫痫发作的保护活性。
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.