HMOX1 and ischemic stroke: Additionally, in an experimental mimic model of ischemic stroke, the upregulation of PI3K/Akt meditated Nrf-2 signaling pathway causes further HO-1 activation and neuroprotective effects (Martin et al., 2004; Wu et al., 2013; Meng et al., 2014; Xu X.H. et al., 2015).