The icv administration of β-End 1–31 or the σ1R agonist PRE084 60 min postsurgery did not alter the extent of infarct volume; however, αN-acetyl β-End 1–31 (3 nmol, icv) greatly reduced stroke outcomes, and much less severe infarction was observed (an approximate 80% reduction in the infarct size to 1.2 ± 0.9% of the total brain volume) after permanent cerebral ischemia. Here, ENG is linked to Stroke.