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 6.4 mg.
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 6 h 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.