Dose-dependent effects of Cerebrolysin® on EEG and short term memory of healthy volunteers during control and hyperventilation induced cerebral ischemia

Cerebrolysin(R), a peptidergic nootropic drug, was to be effective on learning and other cognitive functions in animal experiments as well as in clinical studies. Hyperventilation (HV) as a model of brain ischemia induces slowing of the EEG and cognitive impairment. The aim of this study was to examine the potential dose-dependent effects of Cerebrolysin(R) on HV related EEG changes and short term memory during chronic (10 days) application and the time dependency of these effects. In this single centre, double blind, randomized, placebo-controlled, parallel group study 48 healthy males were enrolled and received either 100 ml placebo (NaCl) or Cerebrolysin(R) (10 ml or 30 ml or 50 ml) in a volume of 100 ml (NaCl) for 10 days. EEG at baseline and during HV as well as the cognitive performance was evaluated at Day 1 (baseline, 15 min p.i., 2h p.i., 4h p.i., 8h p.i., 24h p.i.), Day 10 (baseline, 15 min p.i., 2h p.i.) and at day 11 (24h. after the last infusion). The main effects found during the study can be summarized as follows: At baseline we found an increase of the EEG power ratio (PR) for the grouptrated with 10 ml Cerebrolysin(R). The effect was most pronounced at the parietal cortex. The effect started after 15 min, was most expressed at 2 h and was kept until 8h. During HV we found a relative PR decrease of the group (10 ml Cerebrolysin(R)) at 2 hours. For short term memory, there is a trend towards less effective word recall for the baseline situation during the first 4 hours for the placebo. This effect was not observed in the Cerebrolysin(R) treated groups. If chronic effects are concerned, the PR increased over the parietal regions at 24 h for the groups treated with 10 and 30 ml Cerebrolysin(R) The effect remains at day 10 and 11. But at 10 and 11 days there was also a trend for a relative increase of the PR in the group treated with 50 ml Cerebrolysin(R). Signs of overdosage occurred with the highest concentrations of Cerebrolysin(R). The events were only mild and caused no harm to the volunteers. The highest concentration caused a small but significant reduction of blood pressure. The effects could be interpreted as those of an atypical nootropic with anti-ischemic properties.