ObjectiveGlobal cerebral ischemia is a well-established experimental model for studying hippocampal vulnerability and memory impairment. This study investigated the neuroprotective potential of Kangen-karyu (KK) in a mouse model of global cerebral ischemia/reperfusion injury induced by bilateral common carotid artery occlusion (BCCAO).MethodsMale C57BL/6J mice were subjected to BCCAO followed by reperfusion. KK or nimodipine was administered orally either before or after ischemia. Neurological outcomes, histopathology, and markers of oxidative stress, inflammation, and apoptosis were evaluated.ResultsPost-ischemic administration of KK significantly reduced brain edema, neuronal degeneration, and ischemia/reperfusion-induced brain damage, while improving cognitive performance. These effects were associated with decreased phosphorylation of JNK/p38 MAPK and reduced expression of iNOS and apoptosis-related proteins. Post-treatment produced greater benefits than pre-treatment or nimodipine.ConclusionKK may have therapeutic potential for mitigating global cerebral ischemia/reperfusion-induced brain injury, possibly through modulation of stress- and inflammation-related pathways. Further studies are warranted to validate these findings.