Yunusa_2026_Behav.Brain.Res_514_116354

Vascular dementia (VD) is the second most common form of dementia, mostly affecting the elderly population. Given the complicated neuropathology of VD, there is an urgent need for a novel therapeutic intervention that can target multiple pathways of this disease. This study evaluated the effect of a Bacopa-enriched formulation (BEF) containing Bacopa monnieri, coenzyme Q10, acetyl-L-carnitine, phosphatidylserine, benfotiamine, and methyl folate in a rat 2-vessel occlusion (2VO) model of VD. Male Sprague Dawley rats (200-300 g) were subjected to 2VO surgery and later treated orally with BEF (50, 150, or 300 mg/kg) for 7 consecutive days. Cognitive performance was assessed in the passive avoidance task (PAT) and the Morris water maze (MWM), while neurophysiological functions were evaluated through hippocampal electrophysiology. Rats' hippocampi were isolated, and the effect of the treatments on the level of amyloid-beta, acetylcholine, glutamate, acetylcholinesterase enzyme (AChE) activity, as well as on the expression level of NMDAsigma2, GluR-1, and BDNF was examined using standard protocols. BEF significantly improved memory performance in PAT, MWM and effectively reversed 2VO-induced deficits in long-term potentiation (LTP) and restored basal synaptic transmission. Treatment with BEF reduced amyloid-beta accumulation and normalized glutamate levels, although only minimal effects were observed on acetylcholine concentration and cholinesterase inhibition. Western blot revealed enhanced hippocampal NMDAsigma2 and BDNF but not GluR-1 expression. Motor and exploratory functions remained largely unaffected. Findings from this study suggest BEF's memory enhancement is primarily mediated via modulation of excitatory neurotransmission, enhancement of neuroplasticity, and modification of cognitive function biomarkers, with minimal cholinergic system involvement.