The role of non-neuronal cells in the neuroprotective properties of oestradiol has been recently reviewed63–65 and is not examined here in detail. Our main focus in this Review is the molecular mechanisms elicited by oestradiol in the brain in vivo, in which the cell types involved have not always been identified. However, it should be noted that glial cells express ERs, including ERα, ERβ and GPER64,66,67, and that brain injury induces both the synthesis of oestradiol in reactive astrocytes and the expression of ERs in these cells68. This suggests that astrocytes may play an important part in the neuropro¬tective actions of oestradiol. Indeed, recent studies using conditional knockout mice deficient in either ERα or ERβ have shown that, in an experimental model of multiple sclerosis, the protective action of oestradiol is mediated by ERα expressed in astrocytes but not by ERα expressed in neurons or ERβ expressed in astrocytes or neurons43.