Martín Abraham, Rojas Santiago, Chamorro Angel, Falcón Carles, Bargalló Núria, Planas Anna M
Department of Pharmacology and Toxicology, Institut d'Investigacions Biomèdiques de Barcelona-Consejo Superior de Investigaciones Científicas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barrcelona, Spain.
Stroke. 2006 May;37(5):1288-95. doi: 10.1161/01.STR.0000217389.55009.f8. Epub 2006 Apr 6.
Hyperglycemia adversely affects the outcome of stroke. Global ischemia data support that the harmful effect of hyperglycemia is mediated by glucose-induced elevated plasma glucocorticoids. Here we sought to evaluate the negative effects of hyperglycemia on transient focal ischemia in the rat, and to test whether these could be prevented by inhibition of either corticosteroid production or neutrophil infiltration.
Sprague-Dawley rats (n=217) were used. Ischemia was induced by 1 hour middle cerebral artery occlusion (n=196). Acute hyperglycemia was induced by IP injection of dextrose 30 minutes before ischemia. Neutrophil infiltration was blocked by neutropenia with vinblastine. Corticosterone synthesis was inhibited by chemical adrenalectomy with metyrapone. We measured MRI lesion and tissue infarct volumes, evaluated the neurological function, brain myeloperoxidase and matrix metalloproteinase-9 activities, and protein O-glycosylation.
Hyperglycemia significantly enhanced MRI diffusion-weighted imaging alterations, increased cortical, but not subcortical, infarct volume, worsened neurological score, and enhanced brain myeloperoxidase and matrix metalloproteinase-9 activities. Metyrapone did not prevent hyperglycemic brain damage despite successful reduction of plasma corticosterone. Yet, metyrapone tended to reduce cortical infarction and apparent diffusion coefficient lesion volume, indicating some negative contribution of corticosterone. Blocking neutrophil infiltration was also ineffective to prevent the harmful effect of hyperglycemia. A new finding was that O-linked glycosylation of cerebral proteins was increased under hyperglycemia.
In transient middle cerebral artery occlusion, the hyperglycemia-exacerbated brain damage cannot be fully explained by the negative effects of plasma corticosteroids or neutrophil infiltration. The contribution of other intrinsic effects of high glucose, such as brain protein O-glycosylation, deserves further investigation.
高血糖对卒中结局产生不利影响。全脑缺血数据表明，高血糖的有害作用是由葡萄糖诱导的血浆糖皮质激素升高介导的。在此，我们旨在评估高血糖对大鼠短暂性局灶性缺血的负面影响，并测试抑制皮质类固醇生成或中性粒细胞浸润是否可以预防这些影响。
使用Sprague-Dawley大鼠（n = 217）。通过大脑中动脉闭塞1小时诱导缺血（n = 196）。在缺血前30分钟经腹腔注射葡萄糖诱导急性高血糖。用长春碱诱导中性粒细胞减少以阻断中性粒细胞浸润。用甲吡酮进行化学性肾上腺切除以抑制皮质酮合成。我们测量了MRI病变和组织梗死体积，评估了神经功能、脑髓过氧化物酶和基质金属蛋白酶-9活性以及蛋白质O-糖基化。
高血糖显著增强了MRI弥散加权成像改变，增加了皮质梗死体积，但未增加皮质下梗死体积，恶化了神经评分，并增强了脑髓过氧化物酶和基质金属蛋白酶-9活性。尽管成功降低了血浆皮质酮水平，但甲吡酮并未预防高血糖性脑损伤。然而，甲吡酮倾向于减少皮质梗死和表观扩散系数病变体积，表明皮质酮有一定的负面作用。阻断中性粒细胞浸润也无法有效预防高血糖的有害作用。一项新发现是，高血糖状态下脑蛋白的O-连接糖基化增加。
在短暂性大脑中动脉闭塞中，血浆皮质类固醇或中性粒细胞浸润的负面影响不能完全解释高血糖加剧的脑损伤。高血糖的其他内在影响，如脑蛋白O-糖基化的作用，值得进一步研究。
