Effects of N-(2-propylpentanoyl) urea on impairment of learning memory and neuronal cell death after bilateral common carotic arteries occlusion in mice

Abstract

The present study aimed to investigate the effects of N-(2-propylpentanoyl) urea (VPU) on impairment of learning and memory and neuronal cell death after transient cerebral ischemia (bilateral occlusion of common carotid arteries, 2VO) in mice. The 2VO caused an impairment of learning and memory seen as an increase time to find platform in Morris Water Maze (MWM) test as well as a reduction in latency and an increase in number of errors in passive avoidance (step-down) test. In addition, an increases in brain malondialdehyde (MDA) as well as neuronal cell death in hippocampus CA1 and CA3 regions were also observed. Intraperitoneal administration (i.p.) of VPU or piracetam sigificantly improved performance in MWM test in 2VO mice on day 5 by decreasing the time to find platform. Similar results were observed in step-down test whereby administration of VPU or piracetam significantly increased the step-down latency and a decreased the number of errors in this task. In comparison to 2VO group, administration of VPU and piracetam was found to increase number of survival neurons in CA1 and CA3 regions of hippocampus. Additionally, treatment by VPU or piracetam significantly abolished an increase in MDA induced by 2VO. However, locomotor activity was not altered by neither piracetam nor VPU. Previous report of potentiation of GABA, inhibition of NMDA receptor and reduction of reduction of cortical glutamate elicited by VPU might underlie the neuroprotective effect observed in the present studies. Based on the results obtained, it is suggestive that by means of multi-mechanisms previously reported of VPU, neuroprotective effect was then accomplished resulting in more survival neuronal cells of CA1 and CA3 of the hippocampus. Therefore, impairment of learning and memory induced by 2VO was subsequently improved. Similar to piracetam, VPU might be further developed for post stroke amnesia or anticonvulsant with positive effect on learning and memory.