3-n-Butylphthalide (NBP) attenuated neuronal autophagy and amyloid-β expression in diabetic mice subjected to brain ischemia.

Objective: The aim of this study was to investigate the protective effect of dl-3-n-butylphthalide (NBP) on brain damage in streptozotocin (STZ)-induced diabetic mice subjected to cerebral ischemia.
Methods: we pretreated diabetic mice with NBP orally for 4 weeks prior and 2 days after transient common carotid artery occlusion (CCAO) operation. Immunohistochemistry and transmission electron microscopy were performed to investigate the neuronal loss, astrocytes activation, amyloid-beta (Abeta) protein expression, and autophagy activation.
Results: The results showed that diabetes increased stroke-induced neuronal loss, astrocytes activation, Abeta generation, and autophagy activity, while NBP administration attenuated these changes. Immunofluorescence double staining of Abeta with autophagosome-specific antibody LC3 showed that most elevated Abeta(+) signal was co-localized with LC3(+) signal.
Conclusion: Our finding suggests that NBP attenuates Abeta generation promoted by diabetes in ischemia might act through inhibiting abnormally activated neuronal autophagy. Therefore, treatment with NBP to modulate autophagy might provide a novel therapeutic strategy for diabetes by preventing ischemic brain damage and depressing the risk of post-stroke dementia.