These indirect effects are likely to be important in ischemia, particularly over the longer term, but an important cytoprotective effect of mGluR5 in astrocytes is likely to be direct protection against OGD-induced apoptosis, mediated through PLC and its effects on the PI3K/Akt, Nrf2 and NF-κB pathways [58], [59], [60], [61]. This evidence concerns the gene GRM5 and ischemia.