Stroke is an important medical problem in devel‑
oping countries, characterized by a sudden disruption of blood
supply to the brain, either through occlusion or hemorrhage.
It is a major cause of neurological impairment, resulting in
high medical costs. The present study examined the effect of
6‑gingerol on morphological changes, antioxidant defenses, and
the anti‑apoptotic factors p38 mitogen‑activated protein kinase
(MAPK) and mitofusin (Mfn)2, in a rat model of focal cerebral
ischemia. A total of 60 healthy male Wistar rats were randomly
allocated into six groups: Control, right middle cerebral artery
occlusion (Rt.MCAO) + vehicle, Rt.MCAO + piracetam, and
Rt.MCAO + 6‑Gin 5, 10 and 20 mg/kg BW groups. The results
indicated that 6‑gingerol treatment for a duration of 7 days
reverses morphological alterations, enhances catalase and
glutathione peroxidase activities, reduces Bax, caspase‑3 and
MAPK expression, and increases Bcl‑xL and Mfn2 expres‑
sion in the cortex and hippocampus. In conclusion, 6‑gingerol
demonstrated significant in vivo effectiveness in mitigating
pathological changes induced by cerebral ischemia. This
beneficial effect is attributed, at least in part, to preservation of
antioxidant defenses and activation of anti‑apoptotic pathways.