Bhatia_2020_Int.J.Neurosci__1

The present study investigates the potential of tadalafil, a phosphodiesterase-5 inhibitor, in a rat model of hyperhomocysteinemia induced vascular dementia. Hyperhomocysteinemia induced vascular dementia in Wistar rats was produced by administering L-Methionine (1.7g/kg/day; p.o. x 8 weeks). Learning and memory was assessed by employing Morris water maze (MWM) test. Endothelial dysfunction was assessed through acetylcholine-induced endothelial-dependent vasorelaxation and serum nitrite levels. Various other biochemical and histopathological estimations were also performed. L-Methionine produced significant impairment in acetylcholine-induced endothelium-dependent vasorelaxation and a decrease in serum nitrite levels indicating endothelial dysfunction. Further, these animals performed poorly on Morris water maze, depicting impairment of learning and memory. There was a significant rise in brain oxidative stress level (indicated by an increase in brain thiobarbituric acid reactive species and a decrease in reduced glutathione levels). Increase in brain acetylcholinesterase activity; brain myeloperoxidase activity and brain neutrophil infiltration (a marker of inflammation) were also observed. Tadalafil (5 & 10 mg/kg, p.o.)/donepezil (0.5 mg/kg, i.p., serving as standard) treatment ameliorated L-Methionine induced endothelial dysfunction; memory deficits; biochemical and histopathological changes in a significant manner. It may be concluded that tadalafil has shown efficacy in the rat model of L-Methionine induced vascular dementia and that phosphodiesterase-5 can be considered as an important therapeutic target for the treatment of vascular dementia.