LAUSR

ABSTRACT Excitotoxic damage caused by increased glutamate levels is involved in the pathogenesis of neurodegenerative diseases. Astaxanthin, a natural carotenoid with multiple health benefits, inhibits glutamate release from the brain tissue; however, whether it possesses the ability to affect glutamate‐induced brain injury is unknown. The present study investigated the neuroprotective effects of astaxanthin on kainic acid (KA)‐induced excitotoxicity in rats and the possible underlying intracellular signaling pathway. The rats were orally administrated with astaxanthin (50 or 100mg/kg) for 7 days (once a day), and KA (15mg/kg) was administered intraperitoneally at 1h after the final administration. The results revealed that KA induced seizures, increased the hippocampal glutamate levels, caused considerable neuronal death and microglial activation in the hippocampal CA3 regions, and increased the production of proinflammatory cytokines. Astaxanthin pretreatment prevented these changes. Furthermore, astaxanthin pretreatment increased the expression of neuronal cell survival‐related factors, including phosphorylated Akt, phosphorylated glycogen synthase kinase‐3&bgr;, and Bcl‐2 in the hippocampus of KA‐injected rats. These results suggested that astaxanthin can attenuate seizures, mitigate inflammation, augment survival signals, and prevent hippocampal neuronal damage in the animal model of KA‐induced excitotoxicity. HIGHLIGHTSAstaxanthin pretreatment attenuates KA‐induced seizures and reduces hippocampal glutamate levels.Astaxanthin pretreatment attenuates KA‐induced neuronal cell death and inflammation in the hippocampus.Astaxanthin pretreatment restores the pAkt and pGSK‐3&bgr; levels as well as Bcl‐2 expression reduced by KA administration.