Topical insulin and accumulation of excitotoxic and other amino acids in ischemic rat cerebral cortex

Insulin plays a neuroprotectant role in the brain and spinal cord during is chemia. However, studies have shown insulin to increase the sensitivity of cultured cortical cells to glutamate toxicity. The present study looked at the relationship between topically administered insulin (1 mlU insulin/ml a nd 100 mlU insulin/ml) during a four-vessel model of global ischemia and th e accumulation of amino acids, especially glutamate, from the ischemic rat cerebral cortex. The lower dose of insulin was found to attenuate the relea se of excitotoxic and other amino acids from the cortex in ischemia/reperfu sion. This may occur because insulin increases glucose availability to glia l cells resulting in maintenance of glycolysis and ionic pumps that can red uce glutamate release and maintain uptake during ischemia/reperfusion. The higher dose of insulin, which significantly increased the amount of asparta te, glutamate, taurine, and GABA during reperfusion, may act to stimulate t he amount of glycogen stored in astrocytes, reducing the availability of gl ucose for metabolic purposes.