Ras-GRF1 together with Ras-GRF2 mediates ERK/CREB activation via the N-methyl-D-aspartate glutamate receptor in neurons and was shown to be protective in stroke as Ras-GRF1/Ras-GRF2 double knockout mice had larger infarct volumes compared to wild-type mice after the induction of cerebral ischemia [36]. This evidence concerns the gene MAPK1 and Cerebral ischemia.