Investigating neuroprotective interventions in experimentally induced paradigms of vascular dementia

Abstract

Vascular dementia (VaD) is a chronic, neurocognitive disorder that is caused by cardiovascular or cerebrovascular diseases. VaD patients may suffer from forgetfulness, disorientation, slowed thinking, depression and anxiety, and loss of executive functions like working memory, reasoning, judgment, problem-solving, thinking, planning, and execution of tasks, with performance declining as the task complexity increases. Compared to Alzheimer s disease, VaD receives relatively little research attention. With this background, the present study was carried out to better characterize the molecular mechanisms contributing to neuronal damage in VaD. The neuroprotective effects of dimethyl fumarate (DMF) and 7,8-DHF was studied using the 2-VO model of VaD. DMF increased the antioxidant capacity via Nrf2 pathway activation and reduced expression of downstream inflammatory mediators via inhibition of NF-and#954;B activity. Furthermore, our findings also demonstrated that 7,8-DHF mitigates CCH-induced cognitive impairments and exerted neuroprotective effects by the inhibition of oxidative stress, inflammatory responses, and apoptosis as well as activated the hippocampal AKT/CREB/BDNF signalling pathway. Furthermore, the efficacy of SAC against DOCA salt-induced cognitive deficit in hypertensive rats was also explored. Treatment with SAC attenuated DOCA-salt hypertension-induced learning and memory deficits, reduced BP by inhibiting ACE activity, augmented brain and aorta antioxidant activity and enhanced hippocampal BDNF levels. These results indicate that SAC treatment was able to improve learning and memory in DOCA-salt hypertension-induced VaD rats possibly due to its blood pressure-lowering and neuroprotective effects. Hence, in terms of future perspective, these drugs can potentially be investigated to establish clinical relevance and improve therapeutic outcomes in VaD, newline