Zimmerman G A, Meistrell M, Bloom O, Cockroft K M, Bianchi M, Risucci D, Broome J, Farmer P, Cerami A, Vlassara H
Department of Surgery, North Shore University Hospital, Manhasset, NY 11030, USA.
Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):3744-8. doi: 10.1073/pnas.92.9.3744.
Cerebral infarction (stroke) is a potentially disastrous complication of diabetes mellitus, principally because the extent of cortical loss is greater in diabetic patients than in nondiabetic patients. The etiology of this enhanced neurotoxicity is poorly understood. We hypothesized that advanced glycation endproducts (AGEs), which have previously been implicated in the development of other diabetic complications, might contribute to neurotoxicity and brain damage during ischemic stroke. Using a rat model of focal cerebral ischemia, we show that systemically administered AGE-modified bovine serum albumin (AGE-BSA) significantly increased cerebral infarct size. The neurotoxic effects of AGE-BSA administration were dose- and time-related and associated with a paradoxical increase in cerebral blood flow. Aminoguanidine, an inhibitor of AGE cross-linking, attenuated infarct volume in AGE-treated animals. We conclude that AGEs may contribute to the increased severity of stroke associated with diabetes and other conditions characterized by AGE accumulation.
脑梗死（中风）是糖尿病一种潜在的灾难性并发症，主要原因是糖尿病患者的皮质损失程度比非糖尿病患者更大。这种增强的神经毒性的病因尚不清楚。我们推测，先前已被证明与其他糖尿病并发症发展有关的晚期糖基化终产物（AGEs），可能在缺血性中风期间导致神经毒性和脑损伤。使用局灶性脑缺血大鼠模型，我们发现全身给予AGE修饰的牛血清白蛋白（AGE-BSA）会显著增加脑梗死面积。给予AGE-BSA的神经毒性作用与剂量和时间相关，并与脑血流量反常增加有关。氨基胍是一种AGE交联抑制剂，可减轻AGE处理动物的梗死体积。我们得出结论，AGEs可能导致与糖尿病及其他以AGE积累为特征的疾病相关的中风严重程度增加。
