INSULIN ELEVATES HIPPOCAMPAL GABA LEVELS DURING ISCHEMIA - THIS IS INDEPENDENT OF ITS HYPOGLYCEMIC EFFECT

There are reports that insulin may protect neurons from the effects of ischemia. The mechanisms for this protection are not fully understood . We studied the extracellular levels of glutamate and GABA in insulin -treated animals exposed to transient forebrain ischemia under normogl ycemic and hypoglycemic conditions. In vivo microdialysis technique wa s used to collect extracellular fluid from the CA1 region of the hippo campus. There was a significant increase in GABA levels in the two ins ulin-treated sub-groups compared with the controls. GABA levels were < 1 pmol/10 mu 1 in three 10 min collections prior to ischemia in all t he groups. It increased from 11.1 +/- 3.5 pmol/10 mu l in the conrol g roup to 47 +/- 5 (P < 0.001) in the insulin-treated hypoglycemic group and up to 47.2 +/- 9.3 (P < 0.005) in the insulin-treated normoglycem ic group (two-way ANOVA with repeated measures). Ischemia resulted in an increase in the glutamate levels. The glutamate levels returned to baseline within 30 min of the insult. There were no significant differ ences in the glutamate levels in the three groups. The increase in GAB A concentrations in the extracellular space may result in the inhibiti on of CA1 pyramidal neurons. This may be a possible mechanism of neuro nal protection in animals treated with insulin (with or without being hypoglycemic) during ischemia.