Gender-dependent pathways of hypoxia-ischemia-induced cell death and neuroprotection in the immature P3 rat.

Previously, we demonstrated neuroprotection with 2-iminobiotin (2-IB) after cerebral hypoxia-ischemia (HI) in female, but not in male P7 rats. Given the different patterns of brain injury in more immature rats, we examined whether these gender differences could also be observed in P3 rats. HI was induced by unilateral carotid ligation and FiO2 reduction, followed by 2-IB administration. HSP70 protein expression and cytochrome c release from the mitochondria, markers of short-term outcome, were induced by HI to the same extent in male and female animals. However, reduction in HSP70 production and cytochrome c release by 2-IB was seen in female rats only. Long-term cerebral injury after HI, assessed with histology, was similar in male and female P3 rats, but long-term neuroprotection by 2-IB was observed in female rats only. In conclusion, 2-IB provides neuroprotection after cerebral HI in female, but not in male immature P3 rats.