Tanshinone I alleviates motor and cognitive impairments via suppressing oxidative stress in the neonatal rats after hypoxic-ischemic brain damage

Abstract

Abstract Neonatal hypoxia-ischemia is one of the main reasons that cause neuronal damage and neonatal death. Several studies have shown that tanshinone I (TsI), one of the major ingredients of Danshen, exerts potential neuroprotective effect in adult mice exposed to permanent left cerebral ischemia. However, it is unclear whether administration of TsI has neuroprotective effect on neonatal hypoxic-ischemic brain damage (HIBD), and if so, the potential mechanisms also remain unclear. Here, we reported that treatment with TsI (5 mg/kg, i.p.) significantly alleviated the deficits of myodynamia and motor functions as well as the spatial learning and memory in the rat model of HIBD. These behavioral changes were accompanied by a significant decrease in the number of neuronal loss in the CA1 area of hippocampus. Moreover, ELISA assay showed that TsI significantly increased the production of antioxidants including total antioxidant capacity (T-AOC), glutathione (GSH), total superoxide dismutase (T-SOD) and catalase (CAT), and reduced the production of pro-oxidants including hydrogen peroxide (H2O2), total nitric oxide synthase (T-NOS) and inducible nitric oxide synthase (iNOS). Taken together, these results indicate that TsI presents potential neuroprotection against neuronal damage via exerting significantly antioxidative activity and against pro-oxidant challenge, thereby ameliorating hypoxia-ischemia-induced motor and cognitive impairments in the neonatal rats, suggesting that TsI may be a potential therapeutic agent against HIBD.

Keywords

• Hypoxic-ischemic brain damage
• Tanshinone I
• Learning and memory
• Oxidative stress