The effects of dietary sulfur amino acid deficiency on rat brain glutathione concentration and neural damage in global hemispheric hypoxia-ischemia
The effects of dietary sulfur amino acid deficiency on rat brain glutathione concentration and neural damage in global hemispheric hypoxia-ischemia
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DOI：
10.1080/1028415021000055952
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发表时间：
2002-12-01
影响因子：
3.6
通讯作者：
Paterson, PG
中科院分区：
文献类型：
--
作者：
Bobyn, PJ;Franklin, JL;Paterson, PG
中风中的原发性脑损伤之后是兴奋性毒性级联反应、氧化应激和进一步的神经损伤。谷氨酸是关键的，在氧化应激中耗尽。由于半胱氨酸限制谷胱甘肽的合成，本研究探讨了饮食中的含硫氨基酸（SAA）缺乏对大鼠全脑缺血缺氧模型（GHHI）的神经损伤的影响。用SAA缺乏（“缺乏”）或对照饮食喂养动物3天，使其经受右颈总动脉结扎和缺氧，并且饮食再持续3天。在缺氧-缺血后7天，组织学评估的神经损伤在“缺陷”大鼠中更大，表现为平均（+/- SEM）总体和海马网格评分分别为2.5 +/- 0.7和34.9 +/-9.3%，而对照组的评分分别为0.1 +/- 0.1和0.1 +/-0.1%。在缺氧缺血后6小时，各组之间的平均脑（+/- SEM）还原型谷胱甘肽无差异，但3天后在“缺陷”动物的新皮层中降低（1.46 mumoles/g湿重+/-0.05对比对照组中的1.67 +/-0.04）和丘脑（1.60 mumoles/g湿重+/-0.05对比对照组中的1.78 +/-0.03）。给“缺陷”动物施用半胱氨酸前体并不能改善神经损伤。这些发现表明，营养良好但不“缺乏”的动物可以忍受轻微的脑损伤。“缺乏”动物脑谷胱甘肽的下降可能是几种机制之一。
Primary brain injury in stroke is followed by an excitotoxic cascade, oxidative stress and further neural damage. Glutathione is critical and depleted in oxidative stress. Since cysteine is limiting in glutathione synthesis, this study investigated the effect of dietary sulfur amino acid (SAA) deficiency on neural damage in a rat model of global hemispheric hypoxia-ischemia (GHHI). Animals were fed with SAA deficient ("deficient") or control diet for 3 days, subjected to right common carotid artery ligation and hypoxia, and diet continued for 3 more days. Histologically evaluated neural damage at 7 days post hypoxia-ischemia was greater in "deficient" rats, shown by mean (+/- SEM) global and hippocampal grid scores of 2.5 +/- 0.7 and 34.9 +/- 9.3%, respectively, vs. controls' scores of 0.1 +/- 0.1 and 0.1 +/- 0.1%, respectively. Mean brain (+/- SEM) reduced glutathione was not different between groups at 6 h post hypoxia-ischemia, but was decreased in "deficient" animals 3 days later in neocortex (1.46 mumoles/g wet weight +/- 0.05 vs. 1.67 +/- 0.04 in controls) and thalamus (1.60 mumoles/g wet weight +/- 0.05 vs. 1.78 +/- 0.03 in controls). Administration of a cysteine precursor to "deficient" animals did not ameliorate neural damage. These findings suggest that well-nourished but not "deficient" animals tolerate a mild brain insult. The decline in brain glutathione in the "deficient" animals may be one of several contributing mechanisms.