Interestingly, oestradiol exerts a positive-feedback action on the expression of brain aromatase and ERα in neurons. Thus, aromatase induction after brain injury seems to initiate a cycle that potentiates brain oestra¬diol synthesis and oestradiol-mediated neuroprotective signalling, reducing neurodegeneration. Furthermore, recent studies suggest that brain oestradiol synthesis not only is an endogenous mechanism of neuroprotection but is also essential for the neuroprotective action of hor¬monal oestradiol or oestradiol therapies. Thus, in H19 7 hippocampal cells, the inhibition of aromatase prevents the neuroprotective action of exogenous oestradiol126. In addition, the neuroprotective action of circulating oestradiol in a mouse model of Alzheimer’s disease is significantly reduced in ArKO mice that have undetect¬able levels of brain oestradiol127. Further studies are nec¬essary to clarify the role of brain oestradiol synthesis in the neuroprotective outcome of hormone therapy.