Blood-brain barrier, ion homeostasis and epilepsy: possible implications towards the understanding of ketogenic diet mechanisms
Blood-brain barrier, ion homeostasis and epilepsy: possible implications towards the understanding of ketogenic diet mechanisms
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DOI：
10.1016/s0920-1211(99)00074-1
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发表时间：
1999-12-01
影响因子：
2.2
通讯作者：
Janigro, D
中科院分区：
文献类型：
--
作者：
Janigro, D
癫痫发作改变血脑屏障（BBB）特性的发现激发了人们对脑内皮细胞表型变化可能构成导致癫痫发作的病理引发剂的可能性的兴趣。最近从接受皮质切除术的癫痫患者中获得的证据表明葡萄糖转运蛋白分子（GLUT 1）表达异常，而[F-18]脱氧葡萄糖PET研究表明癫痫灶中葡萄糖摄取减少和代谢低下的区域。癫痫组织中其他“非兴奋性CNS细胞”的特性也发生了改变，癫痫脑中的神经胶质细胞显示出离子稳态能力减弱;电压依赖性机制主要受到影响，增加了对能量依赖性机制的依赖。降低离子稳态与过度活跃的神经元的代谢需求增加一起可能进一步加重葡萄糖摄取机制的BBB损失的神经病理学后果。由于酮体可以提供葡萄糖的替代品来支持大脑的能量需求，因此假设癫痫中生酮饮食的机制之一可能与β-羟基丁酸盐（一种易于在BBB转运的酮体）的可用性增加有关。生酮饮食是葡萄糖转运蛋白综合征和丙酮酸脱氢酶缺乏症的治疗选择，这两种疾病都与脑能量衰竭和癫痫发作有关，这一事实支持了这一假设。(C)1999 Elsevier Science B. V.保留所有权利。
The finding that epileptic seizures alter blood-brain barrier (BBB) properties has stimulated interest into the possibility that phenotypic changes in brain endothelium may constitute a pathological initiator leading to seizures. Recent evidence obtained from epileptic patients undergoing cortical resection, demonstrated abnormal expression of glucose transporter molecules (GLUT1), while [F-18]deoxyglucose PET studies demonstrated regions of decreased glucose uptake and hypometabolism in seizure foci. The properties of other 'nonexcitable CNS cells' are also altered in epileptic tissue, and glial cells from epileptic brain displayed diminished capacity for ionic homeostasis; voltage-dependent mechanisms were primarily affected, increasing reliance on energy-dependent mechanisms. Diminished ion homeostasis together with increased metabolic demand of hyperactive neurons may further aggravate the neuropathological consequences of BBB loss of glucose uptake mechanisms. Since ketone bodies can provide an alternative to glucose to support brain energy requirements, it is hypothesized that one of the mechanisms of the ketogenic diet in epilepsy may relate to increased availability of beta-hydroxybutyrate, a ketone body readily transported at the BBB. This hypothesis is supported by the fact that the ketogenic diet is the treatment of choice for the glucose transporter protein syndrome and pyruvate dehydrogenase deficiency, both associated with cerebral energy failure and seizures. (C) 1999 Elsevier Science B.V. All rights reserved.