We evaluated whether combined treatment with
selegiline, a selective
MAO-B inhibitor, and
EGb 761, a standard extract of Ginkgo biloba, has synergistic effects against ischemic
reperfusion injury (IRI) in gerbils. Interestingly, we observed that pretreatment with
EGb 761 significantly attenuated
selegiline-induced hyperactivity. This finding paralleled striatal
fos-related antigen immunoreactivity (FRA-IR) in mice. Four minutes of bilateral carotid artery occlusion caused substantial cell loss in the CA1 of the hippocampus 5 days post-ischemic insult. Pretreatment with
EGb 761, with or without
selegiline, significantly attenuated this neuronal loss. Combined treatment with
EGb 761 plus
selegiline was more efficacious in preventing this loss. Synaptosomal formations of
protein carbonyl, lipid peroxidation (
malondialdehyde (MDA) + 4-hydroxyalkenal (4-HDA)), and
reactive oxygen species (ROS) in the hippocampus remained elevated 5 days post-ischemic insult. The
antioxidant effects appeared to be most significant in the group treated with
EGb 761 plus
selegiline. This combined treatment produced more significant attenuation of IRI-induced alterations in intramitochondrial
calcium accumulation, the mitochondrial transmembrane potential, and mitochondrial
Mn-superoxide dismutase-like immunoreactivity (
Mn-SOD-IR) than either treatment alone. Our results suggest that co-administration of
EGb 761 and
selegiline produces significant
neuroprotective effects via suppression of oxidative stress and
mitochondrial dysfunction without affecting neurological function.