Summary
The effects of Cerebrolysin® on isolated chicken cortical neurons in an iron induced oxidative stress model and in a combined iron-glutamate model have been examined. In a first part of experiments it has been shown that under low serum conditions exposure of neurons to different concentrations of ammonium-iron(III)citrate (1, 5μM AC-Fe3+) for 8 days caused a significant reduction in neuronal survival. Cerebrolysin® not only prevented iron induced neurodegeneration, demonstrating that ionic iron was responsible for the cell damage, moreover, it increased the neuronal viability up to tenfold with respect to the controls. In the second part of the study neurons pre-incubated for 8 days with AC-Fe3+ were additionally lesioned with 1 mM L-glutamate and allowed to recover for another 48h. Under these conditions cerebrolysin again clearly counteracted the in vitro destructive effects of glutamate. Besides consequences on the viability and survival of neurons Cerebrolysin® increased abundance of the microtubule-associated protein MAP2, which is known to play a an important role in maintaining normal neuronal function.
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References
Berlove D, Caday C, Moskowitz M, Finklestein S (1991) Basic fibroblast growth factor (bFGF) protects against ischemic neuronal death in vivo. Soc Neurosci Abstr 17: 1267
Cheng B, Mattson M (1991) NGF and bFGF protect rat hippocampal and human cortical neurons against hypoglycemic damage by stabilizing calcium homeostasis. Neuron 7: 1031–1041
Cheng B, Mattson MP (1994) NT-3 and BDNF protect CNS neurons against metabolic/excitotoxic insults. Brain Res 640: 56–67
Dexter DT, Carter CJ, Wells FR, Javoy-Agid F, Agid Y, Lees A, Jenner P, Marsden CD (1989) Basal lipid peroxidation in substantia nigra is increased in Parkinson’s disease. J Neurochem 52: 381–389
Dux E, Schubert P, Kreuzberg GW (1992) Ultrastructural localization of calcium in ischemic hippocampal slices: the influence of adenosine and theophylline. J Cereb Blood Flow Metab 12: 520–524
Good PF, Perl DP, Bierer LM, Schmeidler J (1992) Selective accumulation of aluminium and iron in the neurofibrillary tangels of Alzheimer’s disease: a laser microprobe (LAMMA) study. Ann Neurol 31: 286–292
Goodman SR, Zagon IS (1986) The neural cell spectrin skeleton: a review. Am J Physiol 250: 347–360
Gschanes A, Valouskova V, Windisch M (1997) Ameliorative influence of a nootropic drug on motor activity of rats after bilateral carotid artery occlusion. J Neural Transm 104: 1319–1327
Guthrie PB, Segal M, Kater SB (1991) Independent regulation of calcium revealed by imaging dendritic spines. Nature 354: 76–80
Hall DE (1992) Novel inhibitors of iron-dependent lipid peroxidation for neurode-generative disorders. Ann Neurol 32: 137–142
Hutter-Paier B, Grygar E, Windisch M (1996) Death of cultured telencephalon neurons induced by glutamate is reduced by the peptide derivative cerebrolysin. J Neural Transm 47: 267–273
Iacopino AM, Christakos S, Altar CA (1990) NGF augments the calcium binding protein, calbindin-28k, in rat olfactory bulb in vivo. Soc Neurosci Abstr 16: 482
Jellinger K, Kienzl E, Rumpelmair G, Riederer P, Stachelberger H, Ben Shachar D, Youdim BH (1992) Iron-melanin complex in substantia nigra of Parkinsonian brains: an X-ray microanalysis. J Neurochemistry 59: 1168–1171
Kusumoto M, Dux E, Hossmann K-A (1997) Effect of trophic factors on delayed neuronal death induced by in vitro ischemia in cultivated hippocampal and cortical neurons. Metab Brain Dis 12: 113–120
Matesic, Diane F, Rick CS, Lin (1994) Microtubule-associated protein 2 as an early indicator of ischemia-induced neurodegeneration in the gerbil forebrain. J Neurochem 63: 1012–1020
Mattson MP, Zhang Y, Bose S (1993a) Growth factors prevent mitochondrial dysfunction, loss of calcium homeostasis, and cell injury, but not ATP depletion in hippocampal neurons deprived of glucose. Exp Neurol 121: 1–13
Mattson MP, Cheng B (1993b) Growth factors protect neurons against excitotoxic/ ischemic damage by stabilizing calcium homeostasis. Stroke 24: 136–140
Mattson PM, Cheng BIN and Smith-Swintoski VL (1993c) Mechanisms of neurotrophic factor protecting against calcium-and free radical-mediated excitotoxic injury: implications for treating neurodegenerative disorders. Exp Neurol 124: 89–95
Meldrum BS (1990) Protection against ischemic neuronal damage by drugs acting on excitatory neurotransmission. Cerebrovasc Brain Metab Rev 2: 27–57
Monyer H, Hartley DM, Choi DW (1990) 21-aminosteroids attenuate excitoxic neuronal injury in cortical cell cultures. Neuron 5: 121–126
Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65: 55–63
Muller W, Connor JA (1991) Dendritic spines an individual neuronal compartments for synaptic Ca++ responses. Nature 354: 73–76
Nistico G, Ciriolo MR, Fiskin D, Iannone M, DeMartino A, Rotilio G (1992) NGF restores decrease in catalase activity and increases Superoxide dismutase and glutathione peroxidase activity in the brain of aged rats. Free Rad Biol Med 12: 177–181
Olney W (1993) Role of excitotoxins in developmental neuropathology. APMIS 40/101: 103–112
Otto D, Unsicker K (1990) Basic FGF reverses chemical and morphological deficits in the nigrostriatal system of MPTP-treated mice. J Neurosci 10: 1912–1920
Pettmann B, Louis JC, Sensenbrenner M (1979) Morphological and biochemical maturation of neurones cultured in the absence of glial cells. Nature 281: 378–380
Rüther E, Ritter R, Apecechea M, Freytag S, Windisch M (1994) Efficacy of the peptidergic drug cerebrolysin in patients with senile dementia of the Alzheimer’s type (SDAT). Pharmacopsy 27: 32–37
Sandoval IV, Weber K (1978) Calcium-induced inactivation of microtubule formation in brain extracts: presence of a calciumdependent protease acting on polymerization-stimulating microtubule-associated proteins. Eur J Biochem 92: 463–470
Smith MA, Perry G (1995) Free radical damage, iron, and Alzheimer’s disease. J Neurol Sci 134: 92–94
Schwab M, Bauer R, Zwiener U (1997) Physiological effects and brain protection by hypothermia and cerebrolysin after moderate forebrain ischemia in rats. Exp Toxicol Pathol 49: 105–116
Spina MB, Squinto SP, Miller J, Lindsay RM, Hyman C (1992) Brain-derived neurotrophic factor protects dopamine neurons against 6-hydroxydopamine and N-methyl-4-phenyl-pyridinium ion toxicity: Involvement of glutathione system. J Neurochem 59: 99–106
Willmore LJ, Rubin JJ (1982) Formation of malonaldehyde and focal brain edema indced by subpial injection of FeCl2 into rat isocortex. Brain Res 246: 113–119
Zhang Y, Tatsuno T, Carney JM, Mattson MP (1993) Basic FGF, NGF, and IGFs protect hippocampal and cortical neurons against iron-induced degeneration. J Cereb Blood Flow Metabol 13: 378–388
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© 1998 Springer-Verlag Wien
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Hutter-Paier, B., Grygar, E., Frühwirth, M., Temmel, I., Windisch, M. (1998). Further evidence that Cerebrolysin® protects cortical neurons from neurodegeneration in vitro. In: Jellinger, K., Fazekas, F., Windisch, M. (eds) Ageing and Dementia. Journal of Neural Transmission. Supplementa, vol 53. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6467-9_32
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DOI: https://doi.org/10.1007/978-3-7091-6467-9_32
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