Occlusion of a cerebral artery impairs blood flow leading to neuronal death. Reperfusion of the tissue is associated with
inflammation, increased
reactive oxygen species,
necrosis and apoptosis. Hence, damage to the brain will continue even after the blood flow is restored.
Isosteviol has been demonstrated to have protective effects against
ischemia-reperfusion (IR) injury in the rat heart and the current study was undertaken to determine whether it is also effective in preventing IR injury in the brain. Rats were divided into six groups: a
sham-operation control group and 5 IR groups that were pre-treated with either
isosteviol 5 mg.kg (-1), 10 mg.kg (-1), 20 mg.kg (-1),
nimodipine 5 mg.kg (-1), or saline.
Cerebral ischemia was induced for 2 hours. Twenty-two hours after re-perfusion the rats were assessed for neurobehavioral deficit,
infarct volume, histological changes, and
malondialdehyde,
superoxide dismutase (SOD), Bcl-2 and
NF-kappaB levels in brain tissue. Pre-treatment with
isosteviol reduced
infarct volume, ameliorated cell death and infiltration of neutrocytes, improved neuro-locomotor activity, increased SOD activity, induced Bcl-2, suppressed
lipid superoxidation and the expression of
NF-kappaB, and therefore retarded
necrosis and apoptosis of neurons and
inflammation. These positive effects were dose-dependent with an
isosteviol dose of 20 mg.kg (-1), thus being as effective as
nimodipine.