Pankaj Bhatia and Nirmal Singh *
Cerebral hypoperfusion has been associated with increased risk of vascular dementia (VaD). The present study investigates the potential of Tadalafil, a phosphodiesterase-5 inhibitor, in rat model of bilateral common carotid artery occlusion (BCCAo) induced VaD. Wistar rats were subjected to BCCAo procedure under anesthesia to induce VaD. Morris water-maze (MWM) test (7thday onwards post-surgery) was employed to assess learning and memory whereby escape latency time, time spent in target quadrant, Path length and average swim speed taken as important parameters. Endothelial dysfunction was assessed in isolated aorta by observing endothelial dependent acetylcholine induced vasorelaxations and levels of serum nitrite. Various biochemical and histopathological estimations were also performed. BCCAo produced significant impairment in endothelium dependent vasorelaxations and decrease in serum nitrite levels indicating endothelial dysfunction. Further these animals performed poorly on MWM, depicting impairment of learning and memory. There was a significant rise in brain oxidative stress level (indicated by increase in brain thiobarbituric acid reactive species and decrease in reduced glutathione levels). An increase in brain acetylcholinesterase activity was also observed. In addition there was an increase in myloperoxidase activity and neutrophil infiltration in brain (as marker of inflammation). Treatment of Tadalafil (5 & 10 mg/kg, p.o.)/Donepezil (0.5 mg/kg, i.p., serving as standard) ameliorated BCCAo induced endothelial dysfunction; memory deficits; biochemical and histopathological changes in a significant manner. It may be concluded that Tadalafil has shown efficacy in rat model of BCCAo induced VaD and that phosphodiesterase-5 can be considered as an important therapeutic target for the treatment of VaD.
Phosphodieseterase-5, Tadalafil, Oxidative stress, Memory, Vascular DementiPhosphodieseterase-5, Vascular Dementia
Department of Pharmaceutical Sciences and Drug Research, Faculty of Medicine, Punjabi University, Patiala - 147002, Punjab, Department of Pharmaceutical Sciences and Drug Research, Faculty of Medicine, Punjabi university, Patiala- 147002, Punjab