The effect of topical insulin on the release of excitotoxic and other amino acids from the rat cerebral cortex during streptozotocin-induced hyperglycemic ischemia

Insulin has been demonstrated to be neuroprotective in brain and spinal cor d ischemia. The mechanism of neuroprotection may involve alterations in met abolism, protein synthesis or uptake of GABA by astrocytes. Conversely, hyp erglycemia increases the extent of neurologic damage observed during ischem ia/reperfusion. Diabetic patients are 2-4 times more likely to suffer a str oke as normoglycemic patients and they also have worsened neurologic outcom e. Determining if insulin, which many diabetics already use as therapy, can be neuroprotective, would be a possible means of alleviating the detriment al outcome from diabetic stroke. This study looked at the relationship betw een topically administered insulin (1 mIU insulin/ml and 100 mIU insulin/ml ) during a four vessel occlusion model of global ischemia and the release o f amino acids, especially glutamate, from the cortex in streptozotocin (STZ )-treated rats. The rats were utilized either 5-7 days (ASTZ) or 4-6 weeks (CSTZ) after a single STZ injection. In the ASTZ animals both doses of insu lin increased the amount of the excitotoxic amino acids, aspartate and glut amate, released during reperfusion and the higher dose also increased the l evels of taurine and GABA during reperfusion. In the CSTZ animals, both dos es of insulin increased the amount of excitotoxic amino acids during reperf usion and the lower dose increased GABA levels released during reperfusion. The differences between the ACTZ and CSTZ animals may be due to metabolic differences in the utilization of glucose. Insulin may act as a neuroprotec tant by increasing extracellular GABA resulting in neuroinhibition. (C) 200 0 Elsevier Science B.V. All rights reserved.