Nitric Oxide Metabolite Improves Cognitive Impairment by Reducing the Loss of Parvalbumin Inhibitory Interneurons in a Novel Mouse Model of Vascular Dementia

Background: This work aimed to develop a new and simple method to establish a mouse model of vascular dementia (VD). We investigated whether a new nitric oxide metabolite in the botanical mixture (a NO-donating botanical mixture, NOBM) improved learning and memory in mice that underwent bilateral carotid artery stenosis (BCAS). Method: C57BL/6N mice received the NOBM orally (0.1 mL twice a day) after BCAS, from days 1 to 28. We assessed spatial memory using the Y maze and place recognition tests at 1 week and 4 weeks after the induction of BCAS. We quantified the parvalbumin protein in the cortex and hippocampus at 1 week and 4 weeks. We also quantified expression levels of neuronal nuclei, brainderived neurotrophic factor, glial fibrillary acidic protein, and the number of dead neurons performed Fluoro-Jade B staining 31 days after BCAS. Results: NOBM significantly improved learning and memory behaviour in BCAS mice. Immunohistochemistry staining and Western blotting data showed a significantly higher protein expression of parvalbumin in the cortex and hippocampus of NOBM-treated BCAS animals, especially in the early stage of BCAS. Moreover, NOBM reduces neuronal loss in the cortex and reduces neuroinflammation and oxidative stress. The observed effect suggests that the NOBM reduced the loss of parvalbumin inhibitory interneurons in the early stage of VD and inhibited neuroinflammation in the VD mice model. Conclusion: Our results reveal a potential neuroprotective and therapeutic use of NOBM for cognitive dysfunction associated with cerebral hypoperfusion in a mouse model of VD.