Neuronal oestradiol may act as an autocrine or paracrine factor to increase neuronal survival acting on neurons expressing ERs. In this regard, it is of interest that ERα is upregulated in neurons after brain ischaemia and that oestradiol potentiates this upregulation46. In addition, aromatase inhibition results in the downregu¬lation of ERα and the upregulation of ERβ in hippocam¬pal neurons62. Thus, we may envisage a mechanism by which oestradiol, generated by neurons in response to brain injury, enhances further oestradiol production in these cells and at the same time increases oestradiol-mediated neuroprotective signalling by upregulating ERα in neurons.