Effects Of Compound DL0108 On Mitochondria Modulated P-CREB/CRE Signaling Pathway Contribute To Its Neuroprotection Against Cerebral Ischemia In Rats

Background and PurposeCompound DL0108 (pinocembrin) had been found on its neuroprotective effects against glutamate damage in our previous research. In vivo, it had also been proved a potentially beneficial drug for treatment on cerebral ischemia from its neurological protection on ischemia brain in rats. The purpose of this study was to further evaluate its actions on acute and chronic cerebral ischemia in rat, and if it did so, to explore the possible mechanisms mitochondria and related CREB signal pathway involved.MethodsAcute cerebral ischemia and chronic cerebral ischemia were respectively achieved by operation of middle cerebral artery occlusion (MCAO) and bilateral carotid artery ligation (2-VO) in rats. Neurological effects of compound DL0108 were evaluated in animal behavior performances and pathological morphology. Three types of cell including PC12, SH-SY5Y, and primary cortex neuron were cultured, on which established the glutamate and energy deprivation cell model in vitro. Isolated mitochondria from rat brain were detected on structure and function changes by spectrophotometric and fluorescence assay. Immunocytochemical method was used to identify the purity of primary neuron and BDNF/c-FOS expression level. Immunohistochemical and western blotting methods were applied to estimate phosphorated level of cAMP response element binding (CREB) and expression level of its downstream transcription factors. Effects of compound DL0108 on CRE transcription activity were evaluated by luciferase and electro mobility shift assay, simultaneously.ResultsIn vivo, compound DL0108 exhibited neurological protections against both acute cerebral ischemia induced by MCAO and chronic cerebral hypoperfusion induced by 2-VO, including improvement on neurobehavior performances and neuron morphological.