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While the usage of Centella asiatica (CA) is on the increase worldwide, evidence demonstrating its protective efficacy against neurotoxicants is scarce. Hence the present study aimed to understand the neuroprotective efficacy of a standardized aqueous extract of CA against 3-nitropropionic-acid(3-NPA)-induced oxidative stress in the brain of prepubertal mice. We assessed the degree of oxidative stress in cytoplasm of brain regions of male mice (4 wk- old) given CA prophylaxis (5 mg/kg bw) for 10 days followed by 3-NPA administration (i.p.75 mg/kg bw) on the last 2 days. The neurotoxicant elicited marked oxidative stress in the brain of untreated mice as evident by enhanced malondialdehyde levels, reactive oxygen species (ROS) generation, hydroperoxides and protein carbonyls (a measure of protein oxidation) in striatum and other regions (cortex, cerebellum and hippocampus), while CA prophylaxis completely ameliorated the 3-NPA- induced oxidative stress. Depletion of glutathione (GSH) levels, total thiols, perturbations in antioxidant enzymes and cholinergic enzymes in brain discernible among 3-NPA-treated mice were predominantly restored to normalcy with CA prophylaxis. It is hypothesized that the prophylactic protection offered by CA extract against neurotoxicant exposure may be largely due to its ability to enhance GSH, thiols and antioxidant defenses in the brain of prepubertal mice., ((c) 2009 John Wiley & Sons, Ltd.)