NEUROTOXICITY OF ADVANCED GLYCATION ENDPRODUCTS DURING FOCAL STROKE AND NEUROPROTECTIVE EFFECTS OF AMINOGUANIDINE

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 etio logy of this enhanced neurotoxicity is poorly understood. We hypothesi zed that advanced glycation endproducts (AGEs), which have previously been implicated in the development of other diabetic complications, mi ght contribute to neurotoxicity and brain damage during ischemic strok e. Using a rat model of focal cerebral ischemia, we show that systemic ally administered AGE-modified bovine serum albumin (AGE-BSA) signific antly increased cerebral infarct size, The neurotoxic effects of AGE-B SA administration were dose- and time-related and associated with a pa radoxical increase in cerebral blood flow. Aminoguanidine, an inhibito r of AGE cross-linking, attenuated infarct volume in AGE-treated anima ls, We conclude that AGEs may contribute to the increased severity of stroke associated with diabetes and other conditions characterized by AGE accumulation.