Objective To model glucocorticoid-induced cognitive impairment and evaluate the neuroprotection by schi-zandrin (Sch) against dexamethasone (Dex)-induced neurotoxicity in vivo and in vitro. Methods Cerebral cortical cells from neonatal Sprague-Dawley rats (within 24 hours after birth) were cultured for 9 days, and then treated with Dex (10 -4 , 10 -5 , 10 -6 or 10 -7 mol/L) for 24 h or pretreated with 10 -4 mol/L Dex for 24 h followed by 10, 20, 40, or 80 μmol/L Schfor 48 h. Cell viability was assessed using the MTT assay. Immunofluorescence and real-time PCR for MAP2 were performed to confirm the effects of Dex on neurite outgrowth. In vivo, kunming mice were randomly divided into six groups: control [(intragastric (i.g.) vehicle for 42 days]; Dex group I (5 mg/kg·d -1 Dex i.g. treatment for 28 days followed by i.g. vehicle for 14 days); Dex group II (Dex i.g. for 42 days); Dex + Sch (Dex i.g. for 28 days followed by 5, 15, or 45 mg/kg·d -1 Sch i.g. for 14 days). Learning and memory were assessed by Morris water maze test. Histological examination was used to assess pathology and apoptosis in neurons. Results Compared to the Dex groups, Sch increased cell viability in a dose-dependent manner, improved performance in the Morris water maze and ameliorated the morphological changes. Conclusion Sch has neuroprotective effects against insults induced by glucocorticoid.
Xiao XuXing ZhouXiao-Wen ZhouZheng ZhangMin-Jing LiaoQi GaoHuan-Min Luo