Journal of Neural Transmission

, Volume 108, Issue 4, pp 459–473

Antiapoptotic effects of the peptidergic drug Cerebrolysin on primary cultures of embryonic chick cortical neurons

  • M. Hartbauer
  • B. Hutter-Paier
  • G. Skofitsch
  • M. Windisch

DOI: 10.1007/s007020170067

Cite this article as:
Hartbauer, M., Hutter-Paier, B., Skofitsch, G. et al. J Neural Transm (2001) 108: 459. doi:10.1007/s007020170067
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Summary.

Cerebrolysin (EBEWE Arzneimittel, Austria, Europe) is a widely used drug relieving the symptoms of a variety of neurological disorders, particularly of neurodegenerative dementia of the Alzheimer's type. It consists of approximately 25% of low molecular weight peptides (<10 k DA) and a mixture of approximately 75% free amino acids, this being based on the total nitrogen content.

In this study we used a low serum (2% serum supplement) cell stress in-vitro model to assess drug effectiveness on neuronal viability and programmed cell death (PCD). In this in-vitro model the type of cell death was previously shown to be primarly apoptotic, which was verified by DNA-laddering and TUNEL-staining. For evaluation of neuronal viability a MTT-reduction assay was performed after 4 DIV and 8 DIV and the percentage of apoptotic neurons was determined by bis-benzimide staining of nuclear chromatin.

To differentiate between possible effects of the free amino acids and the peptide fraction of Cerebrolysin an artificial amino acid mixture (AA-mix) was used as a control.

Cerebrolysin, the AA-mix and 10% foetal calf serum (FCS) caused a similar increase in viability after 4 DIV, whereas the effects of the growth factors BDNF and FGF-2 were less pronounced. After 8 DIV Cerebrolysin, but not the AA-mix, was able to ameliorate neuronal viability, which could reflect a neuro-protective effect or an increased activity of the mitochondrial dehydrogenase measured in a MTT-reduction assay. The percentage of cells showing apoptotic chromatin changes was significantly reduced (p < 0.01) in cultures treated with Cerebrolysin, whereas the AA-mix failed to decrease the percentage of cells showing apoptotic chromatin changes. These findings ascertain an anti-apoptotic effect of the peptide fraction of Cerebrolysin and reveal a transient viability promoting effect of the amino acid fraction, which is most likely due to improved nutritional supply.

Keywords: Cerebrolysingrowth factorsapoptosischick neuronneuro-protectionserum supplement.

Copyright information

© Springer-Verlag Wien 2001

Authors and Affiliations

  • M. Hartbauer
    • 1
  • B. Hutter-Paier
    • 2
  • G. Skofitsch
    • 4
  • M. Windisch
    • 2
  1. 1.Institute of Zoology, Department of Neurobiology, Karl-Franzens University,
  2. 2.Institute of Experimental Pharmacology, Research Initiative EBEWE,
  3. 3.JSW-Research Ltd, and
  4. 4.Institute of Zoology, Department of Histopharmacology, Karl-Franzens University, Graz, AustriaAT