rhyncophylline and Infarction--Middle-Cerebral-Artery

Previous studies have documented that rhynchophylline exerts antioxidative and anti-inflammatory effects on ischemic neuronal damage in vitro or in vivo. There is a considerable lack of direct evidence for its role in neural function and neuroplasticity after ischemic stroke.. This study aims to explore the role of rhynchophylline in middle cerebral artery occlusion (MCAO) induced ischemic stroke model and the potential mechanisms.. Mice were randomly divided into the following three groups: Sham, MCAO + ddH2O, and MCAO + Rhy(40 mg/kg by oral gavage) groups. Cerebral ischemia was induced by MCAO. Cerebral blood flow was monitored to indicate the success of the ischemic model. The neurological severity score and a series of related behavior tests were performed(after MCAO 3d,7d,14d,21d,28d). Golgi staining and Sholl analysis were used to evaluate the complexity of dendrites and the density of dendritic spines. Immunohistochemistry was used to detect the expression of synapsin I and NeuN.. Administration of rhynchophylline for 7 consecutive days after the onset of cerebral ischemia alleviated the sensory-motor functional defects and ameliorated hippocampus-dependent spatial memory injury as well as reduced the infarct volume induced by MCAO. However, golgi staining and sholl analysis showed that rhynchophylline improved dendritic complexity and spine density as well as the synaptic plasticity. Furthermore,the expression of synapsin I and Neun was significantly reduced after cerebral ischemia and rhynchophylline administration ameliorated the loss of synapsin I.. Rhynchophylline is a promising treatment for ischemic stroke via improving synaptic plasticity and ameliorating the sensory-motor function.

Topics: Animals; Brain Ischemia; Infarction, Middle Cerebral Artery; Ischemic Stroke; Mice; Neuronal Plasticity; Synapsins

The protective effects of gastrodin and rhynchophylline in ischaemic injury have been reported. However, the underlying mechanism and the effect of the combination of these two drugs in ischaemic injury remain unclear. Herein, we aimed to explore the effects of the combination of gastrodin and rhynchophylline on ischaemia-induced inflammasome activation as well as the underlying mechanism.. Middle cerebral artery occlusion (MCAO) mice and oxygen glucose deprivation (OGD)-treated BV2 cells were used as in vivo and in vitro models of ischaemia, respectively. Cerebral injury was determined by TTC staining, H&E staining and neurological deficit scores. The effects of the combination of gastrodin and rhynchophylline on inflammasome activation were measured by the MTT assay, Western blotting and ELISA. The expression of miR-21-5p and miR-331-5p was measured by qRT-PCR. The potential binding between miR-21-5p and TXNIP and between miR-331-5p and TRAF6 was analysed with Targetscan and a luciferase assay.. MCAO-induced tissue infarction, neurological deficits, inflammasome activation, and downregulation of miR-21-5p and miR-331-5p were all mitigated by the combination of gastrodin and rhynchophylline. In OGD-treated BV2 cells, the combination of gastrodin and rhynchophylline also alleviated inflammasome activation and restored the expression of miR-21-5p and miR-331-5p. TXNIP and TRAF6 were confirmed to be targets of miR-21-5p and miR-331-5p, respectively. Moreover, OGD-induced inflammasome activation was attenuated by the overexpression of either miR-331-5p or miR-21-5p and was further attenuated by the overexpression of both. Finally, we demonstrated that a miR-21-5p inhibitor and/or a miR-331-5p inhibitor counteracted the protective effects of gastrodin and/or rhynchophylline.. The combination of gastrodin and rhynchophylline exerts neuroprotective effects by preventing ischaemia-induced inflammasome activation via upregulating miR-21-5p and miR-331-5p.

Topics: Animals; Benzyl Alcohols; Brain Ischemia; Glucosides; Infarction, Middle Cerebral Artery; Inflammasomes; Male; Mice; Mice, Inbred C57BL; MicroRNAs; Neuroprotective Agents; Oxindoles; Transcriptional Activation