Increasing evidence indicates that a healthy diet plays a protective role against ischemic stroke injury. As an antioxidant food, grape powder (GP) has been shown to have a neuroprotective function after ischemic injury. In the current research, we aimed to determine whether regular GP feeding before brain damage plays a protective role against ischemic damage and its potential mechanism. Mice had GP in drinking water (DW) for 4 weeks. Then, fecal samples were collected for 16S rRNA analysis and metabolite profiling. Ischemic stroke was triggered using GP prefeed mice by middle cerebral artery occlusion (MCAo) to compare the stroke-induced infarction size to the DW group. The data showed that 4 weeks of GP pretreatment significantly decreased the ischemic infarct size. Meanwhile, GP treatment altered the gut microbiota by enriching the population of Lachnospiraceae and enhancing a gut metabolite called fiestin, which belongs to the flavonoid group. Mechanistically, we demonstrated that fiestin could inhibit LPS-induced proinflammatory macrophage polarization in vitro. We also showed that regular GP feed could decrease stroke-induced neuroinflammation in vivo. In conclusion, our study demonstrated that 4 weeks of GP feeding attenuates experimental ischemic stroke via the gut-brain-immune axis.

Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective therapy for Parkinson’s disease (PD). However, the therapeutic mechanisms remain incompletely understood, particularly regarding the extracellular space (ECS), a critical microenvironment where molecular diffusion and interstitial fluid (ISF) dynamics are essential for neural function. This study aims to explore the regulatory mechanisms of the ECS in the substantia nigra (SN) of PD rats following STN-DBS. To evaluate whether STN-DBS can modulate ECS diffusion and drainage, we conducted quantitative measurements using a tracer-based magnetic resonance imaging. Our findings indicated that, compared to the PD group, STN-DBS treatment resulted in a decreased diffusion coefficient (D^*), shorted half-life (T_1/2), and increased clearance coefficient (k′) in the SN. To investigate the mechanisms underlying these changes in molecular diffusion, we employed enzyme-linked immunosorbent assay (ELISA), Western blotting (WB), and microdialysis techniques. The results revealed that STN-DBS led to an increase in hyaluronic acid content, elevated expression of excitatory amino acid transporter 2 (EAAT2), and a reduction in extracellular glutamate concentration. Additionally, to further elucidate the mechanisms influencing ISF drainage, we employed immunofluorescence and immunohistochemical techniques for staining aquaporin-4 (AQP-4) and α-synuclein. The results demonstrated that STN-DBS restored the expression of AQP-4 while decreasing the expression of α-synuclein. In conclusion, our findings suggest that STN-DBS improves PD symptoms by modifying the ECS and enhancing ISF drainage in the SN regions. These results offer new insights into the mechanisms and long-term outcomes of DBS in ECS, paving the way for precision therapies.