Rossetti Franco, Rodrigues Marcelo Cairrão Araujo, de Oliveira José Antônio Cortes, Garcia-Cairasco Norberto
Physiology Department, Ribeirão Preto School of Medicine, University of São Paulo, Avenida Bandeirantes 3900, 14049-900 Ribeirão Preto, São Paulo, Brazil.
Epilepsy Res. 2006 Dec;72(2-3):192-208. doi: 10.1016/j.eplepsyres.2006.08.001.
The importance of the substantia nigra pars reticulata (SNPr), striatum (STR) and superior colicullus (SC) in the blockade of experimental seizures is well known. But, in audiogenic seizures (brainstem tonic-clonic seizures), the anticonvulsant activity of these nuclei is still controversial. In the present study we aimed to analyze the STR-SNPr-CS circuitry in the audiogenic seizures of Wistar audiogenic rat (WAR). Behavioral and electroencephalographic (EEG) data were collected from WARs under no treatment or injection with systemic (phenobarbital) or intracerebral (intranigral) drugs (muscimol and phenobarbital). The main EEG frequency oscillation of STR, SNPr and SC seen before, during and after audiogenic seizures or during seizure protection, was determinated with wavelet spectral analyses. This method allows the association between behavior and EEG (video-EEG). Audiogenic seizures last only for half a minute in average, suggesting that the interruptions of seizures are probably not due to exhaustion. Systemic phenobarbital caused an acute and dose-dependent behavioral and EEGraphic anticonvulsant effect both in WARs. The dose of phenobarbital 15mg/kg protected animals almost completely, without side effects such as ataxia and sedation. In our data, this endogenous "natural" seizure blockade (or termination) seems to be similar to the "forced" seizure abolition, like the one caused by a systemic non-ataxic phenobarbital dose, because in both cases an intense decrease in the EEG main frequency oscillation can be seen in SNPr and SC. Intranigral phenobarbital or muscimol did not protect animals, and actually induced an increase in the main EEG frequency oscillation in SC. The main finding of the present study is that, in contrast to what is well believed about the incapacity to control audiogenic seizures by the striato-nigro-tectal circuitry, we collected here evidences that these nuclei are involved in the ability to block these seizures. However, the striato-nigro-tectal circuitry in WARs, a genetically developed strain, seems to have different functional mechanisms when compared with normal rats.
黑质网状部（SNPr）、纹状体（STR）和上丘（SC）在实验性癫痫发作阻断中的重要性已广为人知。但是，在听源性癫痫发作（脑干强直阵挛性发作）中，这些核团的抗惊厥活性仍存在争议。在本研究中，我们旨在分析Wistar听源性大鼠（WAR）听源性癫痫发作中的STR-SNPr-CS神经回路。收集未治疗或注射全身性（苯巴比妥）或脑内（黑质内）药物（蝇蕈醇和苯巴比妥）的WARs的行为和脑电图（EEG）数据。通过小波频谱分析确定听源性癫痫发作前、发作期间和发作后或发作保护期间STR、SNPr和SC的主要EEG频率振荡。该方法允许行为与EEG（视频EEG）之间的关联。听源性癫痫发作平均仅持续半分钟，这表明癫痫发作的中断可能不是由于疲劳。全身性苯巴比妥在WARs中均引起急性且剂量依赖性的行为和脑电图抗惊厥作用。15mg/kg的苯巴比妥剂量几乎完全保护了动物，且没有共济失调和镇静等副作用。在我们的数据中，这种内源性“自然”癫痫发作阻断（或终止）似乎类似于“强制”癫痫发作消除，就像全身性无共济失调苯巴比妥剂量所引起的那样，因为在这两种情况下，SNPr和SC中EEG主要频率振荡均会显著降低。黑质内注射苯巴比妥或蝇蕈醇不能保护动物，实际上还会导致SC中EEG主要频率振荡增加。本研究的主要发现是，与人们普遍认为的纹状体-黑质-顶盖神经回路无法控制听源性癫痫发作相反，我们在此收集到证据表明这些核团参与了阻断这些癫痫发作的能力。然而，与正常大鼠相比，遗传发育的WARs品系中的纹状体-黑质-顶盖神经回路似乎具有不同的功能机制。
