BACKGROUND: Previous studies of curcumin have focused mainly on its cytotoxic properties for antitumor therapy. There are few studies addressing the application of curcumin in the prevention and treatment of nervous system diseases. OBJECTIVE: To observe the protective effect of curcumin against tumor necrosis factor-alpha (TNF-α)-induced neuronal damage in the rat hippocampus and to explore the intervention effect of curcumin on Ca~(2+) influx following neuronal damage. DESIGN, TIME AND SETTING: A cell morphological and physiological study was performed at the Institute of Brain Research, Medical College of Jinan University, China, from December 2006 to June 2007. MATERIALS: Curcumin (Sigma, USA) and TNF-α (Sigma, USA) were used in this study. METHODS: Hippocampal neurons were isolated from one-day neonatal rats and primarily cultured for 5 days. Following this they received 1 μmol/L curcumin and 100 ng/mL TNF-α pre-treatment. Dynamic morphological changes were observed for 1 hour by inverted microscopy. At 48 hours post-treatment, static morphological characteristics of the neurons were observed using inverted microscopy. Subsequently, hippocampal neurons were primarily cultured for 7 days, after receiving 1 μmol/L curcumin and 4.5 ng/mL TNF-α pre-treatment. Intracellular free Ca~(2+) was measured using Fluo 3/acetoxymethyl ester. MAIN OUTCOME MEASURES: Effects of curcumin on TNF-α-induced neuronal damage and Ca~(2+) influx in the rat hippocampus were measured.RESULTS: Following curcumin treatment, TNF-α-induced neurons grew as normal. TNF- α induced a rapid Ca~(2+) influx into the neuronal cytoplasm; however, Ca~(2+) fluorescence intensity only slightly increased when neurons were co-perfused with curcumin and TNF-α. CONCLUSION: Curcumin has a protective effect on rat hippocampal neurons possibly by reducing the TNF-α-induced rapid Ca~(2+) influx into neuronal cytoplasm and by maintaining the Ca~(2+) homeostasis.