Cerebrolysin® protects isolated cortical neurons from neurodegeneration after brief histotoxic hypoxia

Abstract

A brief period of histotoxic hypoxia exhibits certain metabolic features resembling the in vivo situation of ischemia. In this study the neuroprotective effects of the peptidergic nootropic drug Cerebrolysin® (Cere) against iodoacetate induced histotoxic hypoxia were investigated. For that purpose isolated cortical neurons from 9 day chicken embryos were precultured with 0 to 6.4mg·Cere/ml medium. At the 8th day in vitro histotoxic hypoxia was induced by incubation with 0.01 or 0.1 mM iodoacetate. Cells were allowed to recover from toxic stress for 3, 6, 24 or 48 hours. Cere protected neurons dose dependently from delayed neuronal cell death due to 0.01 mM iodoacetate even after a recovery period of 48h. After induction of histotoxic hypoxia by 0.1 mM iodoacetate high concentrations of Cere again led to neuronal protection after the 3 and 6h recovery period. Moreover the influence of Cere on the cytoskeletal protein MAP2 in neurons submitted to 0.01 mM iodoacetate was investigated. With Western blotting and immunohistochemical techniques it has been demonstrated that the drug clearly increased MAP2 abundance after histotoxic hypoxia. The present study points out that after severe damage of cortical neurons with iodoacetate Cere is able to protect neurons from delayed neuronal cell death maybe by maintaining neuronal plasticity due to avoidance of the cytoskeletal breakdown.