Summary
The effects of the peptidergic nootropic drug Cerebrolysin® on spatial memory and motor activity were examined in intact and ischemic rats. Ischemic-hypoxic damage was induced by injection of Na-cyanide followed by bilateral occlusion of common carotid arteries. Immediately afterwards Cerebrolysin® or saline was administered, either by continous intraventricular (i.v.) infusion or by daily intraperitoneal (i.p.) injection. Rats were tested for spatial memory and motor activity in the Morris water maze on days 3 and 4 post-surgery.
The best dose of the substance for i.p. administration was known from previous studies. Therefore we had to investigate the dose-response-relationship and tolerability of the drug after i.v. administration in intact rats. Infusion (i.v.) of a high dose of Cerebrolysin® (0.57mg/day) decreased motor activity and spatial memory of intact rats (p < 0.01 and p < 0.05, respectively) but low dose of Cerebrolysin® was well tolerated in the intact animals.
Ischemia led to deterioration of motor activity in control rats (p < 0.01). Cerebrolysin® significantly counteracted deleterious motor changes due to ischemia up to the level of intact controls after both i.v. infusion (0.0057 mg/ day) and daily i.p. drug administration (100mg/kg bw and day) indicating an accelerating recovery after ischemia.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Akai F, Hiruma T, Sato N, Fujimoto M, Ikou M, Hashimoto S (1992) Neurotrophic factor-like effect of FPF 1070 on septal cholinergic neurons after transections of fimbria-fornix in the rat brain. Histol Histopathol 7: 213–221
Albrecht E, Hingel S, Crailsheim K (1993) The effects of Cerebrolysin on the vitality and sprouting of neurons from cerebral hemispheres and from the brain stem of chicken embryos in vitro. In: Nicolini M, Zatta PF, Coraine B (eds) Alzheimer's disease and related disorders. Pergamon Press, Oxford, pp 341–342
Auer RN, Jensen ML, Whishaw OQ (1989) Neurobehavioral deficit due to ischemic brain damage limited to half of the CA1 sector of the hippocampus. J Neurosci 9: 1641–1647
Baskys A, Wojtowicz MJ (1994) Effects of brain tissue hydrolysate on synaptic transmission in the hippocampus. Pharmacol Biochem Behav 49: 1105–1107
Francis-Turner L, Valoušková V (1996) Nerve growth factor and nootropic drug Cerebrolysin but not fibroblast growth factor can reduce spatial memory impairment elicited by fimbria-fornix transection: short-term study. Neurosci Lett 202: 193–196
Garcia J (1984) Experimental ischemic stroke: a review. Stroke 15: 5–14
Heim C, Sontag KH (1995) Memantine prevents progressive functional neurodegeneration in rats. J Neural Transm 46: 117–130
Hutter-Paier B, Eggenreich U, Windisch M (1996a) Effects of two protein-free peptide derivatives on passive avoidance behaviour of 24-month-old rats. Drug Res 46: 237–241
Hutter-Paier B, Eggenreich U, Windisch M (1996b) Dose-dependent behavioural effects of two protein-free peptide derivatives on the passive avoidance reaction of rats. Drug Res 46: 242–246
Kofler B, Erhart C, Harrer GA (1990) Multidimensional approach in testing nootropic drug effects (Cerebrolysin). Arch Gerontol Geriatr 10: 129–140
Lindner G, Grosse G, Matthies H, Kirsche W (1975) Über die Wirkung von Hirnextrakt und -hydrolysat auf das Nervengewebe unter In-vitro Bedingungen. Z Mikrosk Anat Forsch 89: 815–823
O'Neill M, Allain H, Bentue-Ferrer D, Bellissant E, de Certaines J, Leonard BE (1995) Pharmacological strategies in the treatment of cerebral ischemia. Eur Neurol 35: 28–36
Paier B, Windisch M, Eggenreich U (1992) Postnatal administration of two peptide solutions affect passive avoidance behaviour of young rats. Behav Brain Res 51: 23–28
Palm W (1989) Cerebrolysin-immunization: immunization experiments with 2 batches of Cerebrolysin, a peptide concentrate and an aqueous protein powder extracte (Experts report)
Piswanger A, Paier B, Windisch M (1990) Modulation of protein synthesis in cell-free system from rat brain by Cerebrolysin during development and aging. In: Lubec G, Rosenthal GA (eds) Amino acids. Escom Science Publishers BV, Leiden, pp 651–657
Rüther E, Ritter R, Apecechea M, Freytag S, Windisch M (1994) Efficacy of the peptidergic nootropic drug Cerebrolysin in patients with senile dementia of the Alzheimer type (SDAT). Pharmacopsychiatry 27: 32–40
Schaller R, Schwab M, Bauer R (1993) EEG analysis and comparison to morphological changes after hypoxic ischemic brain injury in rats. In: Rother M, Zwiener U (eds) Quantitative EEG analysis-clinical utility and new methods. Universitätsverlag Jena, Jena, pp 240–244
Schwab M, Bauer R, Zwiener U (1993) Effects of Cere on ECoG during moderate forebrain ischemia under normothermic and hypothermic conditions. In: Eiselt M, Zwiener U, Witte H (eds) Quantitative and topological EEG and MEG analysis. Universitätsverlag Jena, Jena, pp 243–247
Shimazu SN, Tachikawa N, Iwamoto D, Itho T, Komatsu S, Fujimoto M (1992) The neurotrophic and brain protein effect of Cerebrolysin. Neurobiol Aging 13: 107–113
Smith ML, Auer RN, Siesjö BK (1984) The density and distribution of ischemic brain injury in the rat following 2–10 min of forebrain ischemia. Acta Neuropathol 64: 319–332
Sugita Y, Kondo T, Kanazawa A, Itou T, Miyuno Y (1993) Protective effect of FPF 1070 (Cerebrolysin) on delayed neuronal death in the gerbil. Detection of hydroxyl radicals with salycylic acid. Brain Nerve 45: 329–331
Tucker JC, McDaniel WF, Smith SR (1992) A behavioral study of bilateral middle cerebral artery hemorrhagic ischemia in rats. Neuroreport 3: 725–728
Windisch M, Piswanger A (1985a) Effects of a long-term treatment with a peptide derivate on brain metabolism of rats. Drug Res 35: 1353–1356
Windisch M, Piswanger A (1985c) In vitro effects of peptide derivates and extracts from calf blood on the oxidative metabolism of brain, liver and heart muscle homogenates of the rat. Drug Res 35: 87–89
Wenzel J, Stender G, Duwe G (1981) Zur Entwicklung der Neuronenstruktur der Fascia dentata bei der Ratte. Neurohistologisch-morphometrische, ultrastrukturelle und experimentelle Untersuchungen. J Hirnforsch 22: 629–683
Xiong H, Wojtowicz JM, Baskys A (1995) Brain tissue hydrolysate acts on presynaptic adenosine receptors in the rat hippocampus. Can Physiol Pharmacol 73: 1194–1197
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Gschanes, A., Valoušková, V. & Windisch, M. Ameliorative influence of a nootropic drug on motor activity of rats after bilateral carotid artery occlusion. J. Neural Transmission 104, 1319–1327 (1997). https://doi.org/10.1007/BF01294733
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01294733