CENTRALLY ADMINISTERED INSULIN AND IGF-1 IN TRANSIENT FOREBRAIN ISCHEMIA IN FASTED RATS

Based on evidence for a direct central mechanism of insulin action in mitigating damage due to cerebral ischaemia, we have recently shown th at centrally administered insulin, and to a lesser extent, insulin-lik e growth factor-1 (IGF-1), reduce ischaemic damage in fed rats. Becaus e a portion of the neuroprotective effect of insulin may be due to per ipheral hypoglycaemia, we undertook the present series of experiments to determine whether insulin or IGF-1 are neuroprotective in fasted ra ts, which already have low blood glucose values. Continuous minipump d elivery of insulin (1 IU rat(-1) day(-1) n = 13), or IGF-1 (50 mu g ra t(-1) day(-1) n = 10) was compared to control rats treated with phosph ate buffered saline (PBS 25 mu l rat(-1) day(-1) n = 10). Quantitative neuropathology was done one week after 10 min and 15 sec of transient forebrain ischaemia induced by bilateral carotid artery clamping at a mean arterial BP (MABP) of 50 mmHg. In all areas examined i.e. neocor tex, striatum, and hippocampus, the three groups showed similar degree s of necrosis (p > 0.05), although there were insignificant trends for a beneficial effect oi insulin in reducing selective neuronal necrosi s in hippocampus. The results, in combination with previous studies, i ndicate that insulin is more effective in attenuating brain damage in fed rats.