Oestradiol and insulin-like growth factor-1 reduce cell loss after global ischaemia in middle-aged female rats

Whereas the ability of oestradiol and insulin-like growth factor (IGF)-1 to afford neuroprotection against ischaemia-induced neuronal death in young female and male rodents is well established, the impact of IGF-1 in middle-aged animals is largely unknown. The present study assessed the efficacy of oestradiol and IGF-1 with respect to reducing neuronal death after transient global ischaemia in middle-aged female rats after 8 weeks of hormone withdrawal. Rats were ovariohysterectomised and implanted 8 weeks later with an osmotic mini-pump delivering IGF-1 or saline into the lateral ventricle. Some rats also received physiological levels of oestradiol by subcutaneous pellet. Two weeks later, rats were subjected to global ischaemia or sham operation. Surviving hippocampal CA1 neurones were quantified. Ischaemia produced massive CA1 cell death compared to sham-operated animals, which was evident at 14 days. Significantly more neurones survived in animals treated with either oestradiol or IGF-1, but simultaneous treatment produced no additive effect. IGF-1, an endogenous growth factor, may be a clinically useful therapy in preventing human brain injury, with neuroprotective equivalence to oestradiol but without the harmful side-effects.