Tejada S, Roca C, Sureda A, Rial R V, Gamundí A, Esteban S
Laboratori de Neurofisiologia, Departament de Biologia Fonamental i Ciències de la Salut, Universitat de les Illes Balears, Palma de Mallorca, Spain.
Brain Res Bull. 2006 May 15;69(5):587-92. doi: 10.1016/j.brainresbull.2006.03.002. Epub 2006 Mar 29.
Cholinergic and gabaergic systems play an important role generating electroencephalographic activity and regulating vigilance states. Pilocarpine is a cholinergic agonist commonly used to induce seizures and an epilepticus-like state in rodents. A relationship between status epilepticus and reactive oxygen species has been also suggested which could result in seizure-induced neurodegeneration. The aim of this study was to evaluate the existence of oxidative damage as well as the antioxidant enzyme response in cortex and hippocampus after the administration of an intraperitoneal (350 mg/kg) and an intracerebroventricular (360 microg, 1 microl) pilocarpine injection in rats. The GABA agonist muscimol (1 mg/kg, i.p.), with described neuroprotective properties, was used as a negative control. Only systemic pilocarpine induced oxidative damage. Malondialdehyde levels, as a marker of lipid peroxidation (LP), increased in both regions (55-56%). Catalase (52-80%) and superoxide dismutase (53-60%) activities also rose in both regions but glutathione peroxidase activity only increased in cortex (45%). Glutathione reductase and caspase-3 activity did not change. In conclusion, systemic pilocarpine produced oxidative brain damage, whereas local pilocarpine brain injection had no effects. Moreover, the enzymatic determinations performed in this study are a good tool to study brain injury in pharmacological manipulations such as the ones used in short recording EEG studies.
胆碱能和γ-氨基丁酸能系统在产生脑电图活动和调节警觉状态方面发挥着重要作用。毛果芸香碱是一种胆碱能激动剂，常用于诱导啮齿动物癫痫发作和癫痫样状态。癫痫持续状态与活性氧之间的关系也已被提出，这可能导致癫痫发作诱导的神经退行性变。本研究的目的是评估在大鼠腹腔注射（350mg/kg）和脑室内注射（360μg，1μl）毛果芸香碱后，皮质和海马中氧化损伤的存在以及抗氧化酶的反应。γ-氨基丁酸激动剂蝇蕈醇（1mg/kg，腹腔注射）具有所述的神经保护特性，用作阴性对照。只有全身注射毛果芸香碱会诱导氧化损伤。丙二醛水平作为脂质过氧化（LP）的标志物，在两个区域均升高（55-56%）。过氧化氢酶（52-80%）和超氧化物歧化酶（53-60%）的活性在两个区域也均升高，但谷胱甘肽过氧化物酶活性仅在皮质中升高（45%）。谷胱甘肽还原酶和半胱天冬酶-3活性没有变化。总之，全身注射毛果芸香碱会导致脑氧化损伤，而局部脑内注射毛果芸香碱则没有影响。此外，本研究中进行的酶学测定是研究药理学操作中脑损伤的良好工具，例如在短程脑电图记录研究中使用的操作。
