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Basal ganglia neuroprotection with anticonvulsants after energy stress: a comparative study

机译:能量应激后使用抗惊厥药物治疗基底节神经元:对比研究

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摘要

The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model provides a valuable paradigm of the energy deficiency disorders found in childhood. In such disorders, anticonvulsants may provide neuroprotection by modulating cellular energy consumption and by exerting favorable pleiotropic effects on neuronal survival. To verify such hypothesis, we tested the effects of levetiracetam, vigabatrin, gabapentine, pregabaline, tiagabine, clonazepam and lamotrigine on neuroprotection in the MPTP mouse model. The membrane dopamine transporter (DAT) density, which provides a reliable index of dopaminergic neurons survival in the basal ganglia, was assessed by semi-quantitative autoradiography of the striatum. Unlike all other anticonvulsants tested, lamotrigine provided a significant and dose-dependent neuroprotection in these experimental conditions. Lamotrigine, a widely used and well-tolerated molecule in children, could provide neuroprotection in various energy deficiency disorders.
机译:1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)小鼠模型提供了童年时期发现的能量缺乏症的宝贵范例。在此类疾病中,抗惊厥药可通过调节细胞能量消耗并通过对神经元存活发挥有利的多效作用来提供神经保护作用。为了验证这种假设,我们在MPTP小鼠模型中测试了左乙拉西坦,维加巴汀,加巴喷丁,普瑞巴巴林,替加滨,氯硝西am和拉莫三嗪对神经保护的作用。通过纹状体的半定量放射自显影评估膜多巴胺转运蛋白(DAT)密度,该密度提供了基底神经节中多巴胺能神经元存活的可靠指标。与测试的所有其他抗惊厥药不同,拉莫三嗪在这些实验条件下提供了重要的剂量依赖性神经保护作用。拉莫三嗪是儿童中一种广泛使用且耐受性良好的分子,可在多种能量缺乏症中提供神经保护作用。

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