Protective effects of the specific cyclooxygenase-2 inhibitor on microglia activation-mediated neuronal damage

Abstract

Objective To investigate the protective effect of NS398, a specific cyclooxygenase-2 inhibitor, on microglial activation-mediated neuronal damage. Methods The microglia of neonatal SD rat were isolated and cultured in the medium containing 1μg/ml of LPS. The morphological changes of microglial were observed. The IL-1β and TNF-α levels were detected by Western blot in LPS group (group L) and control group (group C). The hippocampal neurons of neonatal SD rats were cultured in the control medium (group C), LPS-activated microglial conditioned medium (group L) and LPS-activated microglial conditioned medium with NS398 (group N ), respectively.The survival rate of neurons were detected by MTT. The respiration of hippocampus neurons was determined by detecting the ratio of lactic acid/pyruvic acid. Results LPS-induced microglial activation was characterized by the morphological change and increased secretion of IL-1β and TNF-α.The survival rate of neurons cultured by microglia activated conditioned medium was 64.37%, while the group N was 80.25%(P<0.01). In group L, the ratio of lactic acid/pyruvic acid (27.34±8.53) was significantly higher than that of group N (20.32±6.05, P<0.01) and group C (14.95±4.72, P<0.01). Conclusion NS398, a specific cyclooxygenase-2 inhibitor, has a protective effect on rat hippocampus neuron damaged by activated microglia. Key words: Cyclooxygenase 2 inhibitors; Microglia; Hippocampus; Neurons