INSULIN REDUCTION OF CEREBRAL INFARCTION DUE TO TRANSIENT FOCAL ISCHEMIA

Insulin has recently been shown to ameliorate damage in models of glob al brain ischemia. To determine whether insulin is also neuroprotectiv e in focal ischemia, 20 rats were given 2 to 3 IU/kg insulin and 10 di d not receive treatment prior to normothermic transient middle cerebra l artery occlusion for 2 hours at a blood pressure of 60 mm Hg. To fur ther elucidate whether infarction volume is influenced by variations i n blood glucose levels within the physiological range, blood glucose w as raised in 10 of the insulin-treated animals to levels comparable wi th the untreated controls. At 1-week survival, damage was assessed usi ng quantitative neuropathological examination of 25 coronal planes. It was found that preischemic insulin lowered the mean intraischemic blo od glucose level from 8.4 +/- 0.2 mM (mu +/- standard error of the mea n) in the control group to 3.4 +/- 0.2 mM and reduced total damage (at rophy plus cortical and striatal necrosis), expressed as the percentag e of the normal hemisphere, from a control of 28.5% +/- 2.9% to 14.5% +/- 1.6% (p < 0.005). Coadministration of glucose and insulin resulted in a mean intraischemic blood glucose level of 10.1 +/- 0.5 mM, with 27.0% +/- 2.4% total damage (p = 0.96, compared with control). Total i schemic damage showed an independent correlation with blood glucose le vels (r = 0.67, p = 0.0018). The findings indicate that insulin benefi ts transient focal ischemia and that reducing the blood glucose from 8 to 9 mM to the low-normal range of 3 to 4 mM with insulin dramaticall y reduces subsequent infarction. The data suggest that the neuroprotec tive mechanism of insulin action in focal middle cerebral artery occlu sion is mediated predominantly via alterations in blood glucose levels . In comparison to global ischemia, focal ischemia appears to show onl y a minor direct central nervous system effect of insulin. In clinical situations in which transient focal ischemia to the hemisphere can be anticipated, insulin-induced hypoglycemia of a mild degree may be ben eficial.