Neuroprotective effects of enriched environment housing after transient global cerebral ischaemia are associated with the upregulation of insulin-like growth factor-1 signalling




Use of enriched environment (EE) housing has been shown to promote recovery from cerebral ischaemic injury but the underlying mechanisms of their beneficial effects remains unclear. Here we examined whether the beneficial effects of EE housing on ischaemia-induced neurodegeneration and cognitive impairment are associated with increased insulin-like growth factor-1 (IGF-1) signalling in the hippocampus.


Forty-two adult male Wistar rats were included in the study and received either ischaemia or sham surgery. Rats in each group were further randomized to either: EE or standard laboratory cage housing (control). Rats were placed in their assigned housing condition immediately after recovery from anaesthesia. Behavioural testing in the cued learning and discrimination learning tasks were conducted 2 weeks after ischaemia. Rats were euthanized after behavioural testing and the hippocampus was analysed for IGF-1 level, IGF-1 receptor (IGF-1R) activation, protein kinase B (Akt) pathway activation, neurone loss and caspase 3 expression.


Our data showed that EE housing: (1) mitigated ischaemia-induced neuronal loss; (2) attenuated ischaemia-induced increase in caspase 3 immunoreactivity in the hippocampus; (3) ameliorated ischaemia-induced cognitive impairments; and (4) increased IGF-1R activation and signalling through the Akt pathway after ischaemic injury.


Ultimately, these findings suggest the possibility that IGF-1 signalling may be one of the underlying mechanisms involved in the beneficial effects of EE in optimizing recovery following cerebral ischaemic injury.