Neurotoxicity of advanced glycation endproducts during focal stroke and neuroprotective effects of aminoguanidine

Gary A. Zimmerman, Malcolm Meistrell, Ona Bloom, Kevin M. Cockroft, Marina Bianchi, Donald Risucci, John Broome, Peter Farmer, Anthony Cerami, Helen Vlassara, Kevin J. Tracey

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)3744-3748
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number9
DOIs
StatePublished - Apr 25 1995

All Science Journal Classification (ASJC) codes

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    Zimmerman, G. A., Meistrell, M., Bloom, O., Cockroft, K. M., Bianchi, M., Risucci, D., Broome, J., Farmer, P., Cerami, A., Vlassara, H., & Tracey, K. J. (1995). Neurotoxicity of advanced glycation endproducts during focal stroke and neuroprotective effects of aminoguanidine. Proceedings of the National Academy of Sciences of the United States of America, 92(9), 3744-3748. https://doi.org/10.1073/pnas.92.9.3744