Efficacy of Antioxidant Therapies in Transient Focal Ischemia in Mice

Abstract

Background and Purpose-Ginkgo biloba extract (EGb) and ␣-lipoic acid (LA) are commercially available "antioxidant supplements" with a variety of actions that may be beneficial during acute stroke. These actions include inhibiting platelet and leukocyte activation and adhesion, reducing free radical generation, and increasing cerebral blood flow. Both EGb and LA have been shown to be neuroprotective in cell culture and global central nervous system ischemia models. In this study we investigated the neuroprotective efficacy of EGb and LA in a clinically relevant, transient focal central nervous system ischemic model. Methods-In the EGb study, 60 adult C57blk mice were randomized to treatment with EGb given orally (via gavage) for 7 days: low dose, 50 EGb mg/kg daily; high dose, 100 mg/kg daily; matched placebo. On day 7, reversible middle cerebral artery occlusion was produced by advancing a silicone-coated 8-0 filament into the internal carotid artery for 45 minutes followed by reperfusion. At 24 hours, the animals were evaluated on a 28-point clinical scale, and infarct volume was determined with the use of triphenyltetrazolium chloride. In the LA study, 24 C57blk mice were treated with 100 mg/kg SC of LA or placebo 1.5 hours before transient MCAO, as in the EGb study.

α-lipoic acid protects against cerebral ischemia/reperfusion-induced injury in rats

“…Therefore, as a preventive agent, LA is beneficial to cerebral I/R-induced injury. This finding is consistent with previous studies on the beneficial effects of LA against cerebral ischemia (21,22). The results demonstrated that the optimal dose of LA was 100 mg/kg.…”

A multifunctional cytoprotective agent that reduces neurodegeneration after ischemia

“…On the other hand, hypoxia is likely to play an important role in neuronal death, especially at the periphery of the infarct. The in vivo neuroprotective efficacy of PAN-811 is now clearly established, and its ability to be used subsequent to arterial occlusion distinguishes it from many other neuroprotectants such as antioxidants, ginkgo biloba extract, and ␣-lipoic acid (26). It is also superior to the manganese superoxide dismutase mimetic M40401, which is reported to reduce MCAoinduced infarct volume by 73% when animals are pretreated but fails to reduce lesion volume significantly when administered subsequent to MCAo (27).…”

Effect of Ginkgo biloba on brain volume after carotid artery occlusion in rats: a stereological and histopathological study

“…Histopathological studies performed with a cerebral ischemia model have determined pronounced contraction in neurons, irregularities in cell and nuclear margins, and perineural and pericapillary edema. Some of these studies reported a decrease in cerebral cortex and hippocampus neuron numbers and infarct in the area of ischemia (27,28). A very few studies have shown that GB has a protective effect against ischemia-associated damage in neurons.…”