Hyperhomocysteinemia (hHcy) represents a strong risk factor for atherosclerosis-associated diseases, like stroke, dementia or Alzheimer’s disease. A methionine (Met)-rich diet leads to an elevated level of homocysteine in plasma and might cause pathological alterations across the brain. The hippocampus is being constantly studied for its selective vulnerability linked with neurodegeneration. This study explores metabolic and histo-morphological changes in the rat hippocampus after global ischemia in the hHcy conditions using a combination of proton magnetic resonance spectroscopy and magnetic resonance-volumetry as well as immunohistochemical analysis. After 4 weeks of a Met-enriched diet at a dose of 2 g/kg of animal weight/day, adult male Wistar rats underwent 4-vessel occlusion lasting for 15 min, followed by a reperfusion period varying from 3 to 7 days. Histo-morphological analyses showed that the subsequent ischemia-reperfusion insult (IRI) aggravates the extent of the sole hHcy-induced degeneration of the hippocampal neurons. Decreased volume in the grey matter, extensive changes in the metabolic ratio, deeper alterations in the number and morphology of neurons, astrocytes and their processes were demonstrated in the hippocampus 7 days post-ischemia in the hHcy animals. Our results suggest that the combination of the two risk factors (hHcy and IRI) endorses and exacerbates the rat hippocampal neurodegenerative processes.

中文翻译：

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蛋氨酸饮食对全脑缺血模型大鼠海马时间相关代谢和组织病理学变化的影响。

高同型半胱氨酸血症（hHcy）代表与动脉粥样硬化相关的疾病（例如中风，痴呆或阿尔茨海默氏病）的强烈危险因素。富含蛋氨酸（Met）的饮食会导致血浆中同型半胱氨酸水平升高，并可能引起大脑的病理变化。海马因其与神经退行性变有关的选择性脆弱性而被不断研究。这项研究探索质子磁共振波谱和磁共振波谱分析以及免疫组化分析相结合的hHcy条件下全局缺血后大鼠海马的代谢和组织形态变化。4周后，一成年雄性Wistar大鼠以2 g / kg动物体重/天的剂量富含Met饮食，进行4血管闭塞，持续15分钟，然后再灌注期为3至7天。组织形态学分析表明，随后的缺血再灌注损伤（IRI）加剧了hHcy诱导的海马神经元变性的程度。在hHcy动物缺血后7天，海马中灰质体积减少，代谢率发生广泛变化，神经元，星形胶质细胞及其过程的数量和形态发生更深的变化。我们的结果表明，两种危险因素（hHcy和IRI）的组合支持并加剧了大鼠海马神经退行性过程。