Stroke neuroprotection: oestrogen and insulin-like growth factor-1 interactions and the role of microglia

Oestrogen has been shown to be neuroprotective for stroke and other neural injury models. Oestrogen promotes a neuroprotective phenotype through myriad actions, including stimulating neurogenesis, promoting neuronal differentiation and survival, suppressing neuroinflammation and maintaining the integrity of the blood-brain barrier. At the molecular level, oestrogen directly modulates genes that are beneficial for repair and regeneration via the canonical oestrogen receptor. Increasingly, evidence indicates that oestrogen acts in concert with growth factors to initiate neuroprotection. Oestrogen and insulin-like growth factor (IGF)-1 act cooperatively to influence cell survival, and combined steroid hormone/growth factor interaction has been well documented in the context of neurones and astrocytes. Here, we summarise the evidence that oestrogen-mediated neuroprotection is critically dependent on IGF-1 signalling, and specifically focus on microglia as the source of IGF-1 and the locus of oestrogen-IGF-1 interactions in stroke neuroprotection.