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Original Article

Topical Insulin and Accumulation of Excitotoxic and Other Amino Acids in Ischemic Rat Cerebral Cortex

L. L. Guyot^*,, F. G. Diaz^*, M. H. O'regan, D. Song and J. W. Phillis^,1

^* Departments of Neurological Surgery and
Physiology, School of Medicine, Wayne State University, Detroit, Michigan 48201; and
Biomedical Sciences, University of Detroit Mercy School of Dentistry, Detroit, Michigan 48129

Insulin plays a neuroprotectant role in the brain and spinal cord during ischemia. 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 mIU insulin/ml and 100 mIU insulin/ml) during a four-vessel model of global ischemia and the accumulation of amino acids, especially glutamate, from the ischemic rat cerebral cortex. The lower dose of insulin was found to attenuate the release of excitotoxic and other amino acids from the cortex in ischemia/reperfusion. This may occur because insulin increases glucose availability to glial cells resulting in maintenance of glycolysis and ionic pumps that can reduce glutamate release and maintain uptake during ischemia/reperfusion. The higher dose of insulin, which significantly increased the amount of aspartate, glutamate, taurine, and GABA during reperfusion, may act to stimulate the amount of glycogen stored in astrocytes, reducing the availability of glucose for metabolic purposes.

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