A randomized, double-blind, placebo-controlled trial with cerebrolysin in Alzheimer's disease

Abstract

In an attempt to compare effects of different neurotrophic factors on impaired memory function, young adult naive rats were trained to find the hidden platform in the Morris water maze (3 consecutive days, eight trials/day). The fimbria-fornix was unilaterally removed by aspiration and nerve growth factor (NGF) (11 μg/ml and 0.5 μg/ml; groups NGF and ngf, respectively) or basic fibroblast growth factor (bFGF) (0.2 μg/ml, group FGF) were applied via intra-cerebroventricular infusion by the osmotic minipump (flow rate 0.5 μl/h, 14 days). Nootropic drug Cerebrolysin (EBEWE Arzneimittel; 2.5 ml/kg/day, group CER) was applied via intraperitoneal injection (14 days). One group was formed by the rats treated with NGF (11 μg/ml) and Cerebrolysin (group NGFCER). Non-lesioned and lesioned only rats served as controls (groups INT and LES). After a 14-day treatment, rats were tested using the retention test (1 day, four trials). On the next day, the rats were tested using transfer test (3 days, eight trials/day). Escape latency and length of trajectory was recorded. Groups NGF, ngf, FGF and LES were similarly impaired in their ability to retrieve the old position of the platform (retention test), as well as in their ability to navigate to the new position of the platform (transfer test). In the latter, NGF group significantly differed from lesioned animals. Groups CER and NGFCER were comparable to group INT in the retention or transfer test. It is concluded that anterograde amnesia elicited by fimbria-fornix lesion can be abbreviated by NGF and/or CER, while retrograde amnesia is absent only in rats treated by CER. No short-term influence of bFGF was found. It is suggested that biochemical systems other than the cholinergic one are involved.