Research ReportNetrin-1 improves spatial memory and synaptic plasticity impairment following global ischemia in the rat

Cerebral ischemia, which is the second and most common cause of mortality, affects millions of individuals worldwide. The present study was performed to investigate whether intrahippocampal administration of netrin-1 could improve spatial memory impairment in radial arm maze task and restore long-term potentiation (LTP) in 4-vessel occlusion model of global ischemia. The results showed that intrahippocampal infusion of nerin-1 24 h after ischemia (at both doses of 400 and 800 ng) significantly ameliorated spatial memory impairment and at a dose of 800 ng was capable to improve synaptic dysfunction as observed by recovery of population spike component of basal evoked potential and LTP through enhancement of excitability and normalization of paired pulse response. Taken together, the present study shows that netrin-1 dose-dependently ameliorates spatial memory impairment and improves synaptic dysfunction as observed by recovery of population spike component of basal evoked potential and LTP in rats with global ischemia.

► Rats with global ischemia showed a higher number of working and reference errors and a greater latency in radial arm maze. ► HFS did not induce a synaptic potentiation of excitatory post synaptic potential and population spike in global ischemia. ► Post-ischemic intrahippocampal infusion of nerin-1 ameliorated spatial memory impairment in radial arm maze task. ► Nerin-1 partially restores LTP through enhancement of excitability and normalization of paired pulse response.