The effects of glycemic control on seizures and seizure-induced excitotoxic cell death.
The effects of glycemic control on seizures and seizure-induced excitotoxic cell death.
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DOI：
10.1186/1471-2202-13-94
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发表时间：
2012-08-06
期刊：
影响因子：
2.4
通讯作者：
Schauwecker PE
中科院分区：
文献类型：
--
作者：
Schauwecker PE
癫痫是中风后最常见的神经系统疾病，影响全球超过5000万人。代谢紊乱通常与癫痫发作有关，但这种关系的发病机制知之甚少。已知癫痫发作导致葡萄糖代谢改变，细胞内能量代谢物如ATP、ADP和磷酸肌酸的减少以及代谢中间产物如乳酸盐和腺苷的积累。特别是，它已被建议，葡萄糖失调的持续时间和程度可能是一个预测的病理结果的状态。然而，关于血糖控制对脑代谢的影响以及癫痫患者管理全身葡萄糖浓度的影响，我们知之甚少。在这项研究中，我们研究了葡萄糖调制红藻氨酸诱导的癫痫发作的敏感性及其神经病理后果。为了研究血糖调节、癫痫易感性及其神经病理学后果之间的关系，使C57 BL/6小鼠（兴奋性毒素细胞死亡抗性）经受低血糖或高血糖，随后全身施用红藻氨酸以诱导癫痫发作。无论红藻氨酸盐给药前小鼠是低血糖还是高血糖，甘氨酸调节导致癫痫发作严重程度方面的后果最小，但增加海马病理学。此外，我们发现红藻氨酸癫痫发作后外源性葡萄糖给药显著降低了红藻氨酸全身给药后FVB/N小鼠（兴奋性毒素细胞死亡易感）海马病理学的程度。这些发现表明，血糖指数的调制可以改变癫痫发作诱导的红藻氨酸盐模型中的脑损伤的结果。此外，通过葡萄糖救援的血糖指数的调制大大降低了红藻氨酸盐给药后的尿素诱导的细胞死亡的程度。我们的数据支持这一假设，即胰岛素信号传导缺陷可能是糖尿病诱导细胞死亡易感性的关键因素，这可能是一个重要的治疗靶点。
Epilepsy is the most common neurological disorder after stroke, affecting more than 50 million persons worldwide. Metabolic disturbances are often associated with epileptic seizures, but the pathogenesis of this relationship is poorly understood. It is known that seizures result in altered glucose metabolism, the reduction of intracellular energy metabolites such as ATP, ADP and phosphocreatine and the accumulation of metabolic intermediates, such as lactate and adenosine. In particular, it has been suggested that the duration and extent of glucose dysregulation may be a predictor of the pathological outcome of status. However, little is known about neither the effects of glycemic control on brain metabolism nor the effects of managing systemic glucose concentrations in epilepsy. In this study, we examined glycemic modulation of kainate-induced seizure sensitivity and its neuropathological consequences. To investigate the relationship between glycemic modulation, seizure susceptibility and its neuropathological consequences, C57BL/6 mice (excitotoxin cell death resistant) were subjected to hypoglycemia or hyperglycemia, followed by systemic administration of kainic acid to induce seizures. Glycemic modulation resulted in minimal consequences with regard to seizure severity but increased hippocampal pathology, irrespective of whether mice were hypoglycemic or hyperglycemic prior to kainate administration. Moreover, we found that exogenous administration of glucose following kainic acid seizures significantly reduced the extent of hippocampal pathology in FVB/N mice (excitotoxin cell death susceptible) following systemic administration of kainic acid. These findings demonstrate that modulation of the glycemic index can modify the outcome of brain injury in the kainate model of seizure induction. Moreover, modulation of the glycemic index through glucose rescue greatly diminishes the extent of seizure-induced cell death following kainate administration. Our data support the hypothesis that deficient insulin signaling may represent a critical contributing factor in the susceptibility to seizure-induced cell death and this may be an important therapeutic target.
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影响因子：
5.3
作者：
DAVENPORT, CJ;BROWN, WJ;BABB, TL
通讯作者：
BABB, TL
影响因子：
4.7
作者：
CHAPMAN, AG;ENGELSEN, B;MELDRUM, BS
通讯作者：
MELDRUM, BS
影响因子：
5.3
作者：
Friberg, H;Ferrand-Drake, M;Wieloch, T
通讯作者：
Wieloch, T
DOI：
10.1111/j.1432-1033.1988.tb14475.x
发表时间：
1988-12-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
CROMPTON, M;COSTI, A
通讯作者：
COSTI, A
影响因子：
4.7
作者：
Faraco, G.;Fossati, S.;Chiarugi, A.
通讯作者：
Chiarugi, A.