Edaravone Dexborneol Alleviates Neuroinflammation by Reducing Neuroglial Cell Proliferation and Suppresses Neuronal Apoptosis/Autophagy in Vascular Dementia Rats.

More and more evidence shows that the pathological mechanism of vascular dementia (VD) is closely related to oxidative stress injury, cell apoptosis, autophagy, inflammatory response, excitatory amino acid toxicity, synaptic plasticity change, calcium overload, and other processes. Edaravone dexborneol (EDB) is a new type of neuroprotective agent that can improve the neurological damage caused by an ischemic stroke. Previous studies showed that EDB has effects on synergistic antioxidants and induces anti-apoptotic responses. However, it remains unclear whether EDB can affect apoptosis and autophagy by activating the PI3K/Akt/mTOR signaling pathway and its impact on the neuroglial cells. In this study, we established the VD model of rats by bilateral carotid artery occlusion to explore the neuroprotective effect of EDB and its mechanism. Morris Water Maze test was applied to assess the cognitive function of rats. H&E and TUNEL staining were applied to observe the cellular structure of the hippocampus. Immunofluorescence labeling was used to observe the proliferation of astrocytes and microglia. ELISA was applied to examine the levels of TNF-α, IL-1β and IL-6, and RT-PCR was applied to examine their mRNA expression levels. Western blotting was applied to examine apoptosis-related proteins (Bax, Bcl-2, Caspase-3), autophagy-related proteins (Beclin-1, P62, LC3B), PI3K/Akt/mTOR signaling pathway proteins and their phosphorylation levels. The results indicated that EDB ameliorates learning and memory in rats subjected to the VD model, alleviates neuroinflammatory response by reducing the proliferation of the neuroglial cell and inhibits apoptosis and autophagy, which may be mediated by the PI3K/Akt/mTOR signaling pathway.