Departamento de Neuroquímica Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez,14269 Ciudad de México, Mexico; Laboratorio de Neurofarmacología Molecular, Universidad Autónoma Metropolitana Xochimilco,04960 Ciudad de México, Mexico.
Departamento de Neuroquímica Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez,14269 Ciudad de México, Mexico.
Brain Res. 2023 Mar 15;1803:148227. doi: 10.1016/j.brainres.2022.148227. Epub 2022 Dec 30.
Development of effective drugs for epilepsy are needed, as nearly 30 % of epileptic patients, are resistant to current treatments. This study is aimed to characterize the anticonvulsant effect of dapsone (DDS), in the kainic acid (KA)-induced Status Epilepticus (SE) by recording the brain metabolic activity with an [F]FDG-PET analysis.
Wistar rats received KA (10 mg/kg, i.p., single dose) to produce sustained seizures. [F]FDG-PET and electroencephalographic (EEG) studies were then performed. DDS or vehicle were administered 30 min before KA. [F]FDG uptake and EEG were evaluated at baseline, 2 and 25 h after KA injection. Likewise, caspase-8, 3 hippocampal activities and Fluoro-Jade B neuronal degeneration and Hematoxylin-eosin staining were measured 25 h after KA.
PET data evaluated at 2 h showed hyper-uptake of [F]FDG in the control group, which was decreased by DDS. At 25 h, hypo-uptake was observed in the control group and higher values due to DDS effect. EEG spectral power was increased 2 h after KA administration in the control group during the generalized tonic-clonic seizures, which was reversed by DDS, correlated with [F]FDG-PET uptake changes. The values of caspases-8 activity decreased 48 and 43 % vs control group in the groups treated with DDS (12.5 y 25 mg/kg respectively), likewise; caspase-3 activity diminished by 57 and 53 %. Fewer degenerated neurons were observed due to DDS treatments.
This study pinpoints the anticonvulsant therapeutic potential of DDS. Given its safety and effectiveness, DDS may be a viable alternative for patients with drug-resistant epilepsy.
需要开发有效的抗癫痫药物，因为近 30%的癫痫患者对当前的治疗方法有抗药性。本研究旨在通过 [F]FDG-PET 分析来记录脑代谢活性，以研究氨苯砜（DDS）对海人酸（KA）诱导的癫痫持续状态（SE）的抗惊厥作用。
Wistar 大鼠腹腔注射 KA（10mg/kg，单次剂量）以产生持续的癫痫发作。然后进行 [F]FDG-PET 和脑电图（EEG）研究。DDS 或载体在 KA 前 30 分钟给药。在 KA 注射后 2 和 25 小时评估 [F]FDG 摄取和 EEG。同样，在 KA 后 25 小时测量海马 caspase-8、3 的活性以及 Fluoro-Jade B 神经元变性和苏木精-伊红染色。
PET 数据在 2 小时评估时显示对照组 [F]FDG 摄取增加，DDS 降低了这种增加。在 25 小时时，对照组观察到低摄取，由于 DDS 的作用导致摄取增加。在对照组中，KA 给药后 2 小时观察到 EEG 谱功率增加，在全面强直阵挛性癫痫发作期间，DDS 逆转了这种增加，与 [F]FDG-PET 摄取变化相关。与对照组相比，DDS（分别为 12.5 和 25mg/kg）治疗组的 caspase-8 活性分别降低了 48%和 43%，同样，caspase-3 活性降低了 57%和 53%。由于 DDS 治疗，观察到的变性神经元减少。
本研究指出了 DDS 的抗惊厥治疗潜力。鉴于其安全性和有效性，DDS 可能是耐药性癫痫患者的可行选择。
