Церебролизин: обзор литературы (часть I)

Как показывают результаты анализа экспериментальных и клинических исследований, применение церебролизина является эффективной и безопасной терапией при многих неврологических расстройствах, начиная от инсульта и заканчивая болезнью Альцгеймера. Первичный эффект препарата связан с влиянием церебролизина на определенные зоны гиппокампа и их функцию. Препарат обладает уникальным органоспецифическим мультимодальным действием на головной мозг, способен к метаболической регуляции, нейропротекции, функциональной нейромодуляции и нейротрофической активности, установленным в многочисленных экспериментальных исследованиях. Клиническая эффективность препарата подтверждена в ходе клинических испытаний, проводившихся с учетом требований GCP. Побочные эффекты препарата незначительны.

церебролизин, лекарственная терапия, психиатрия, неврология, фармакология, нейропротектор, метаболическая регуляция, функциональная нейромодуляция, нейротрофическая активность, cerebrolysin, medical therapy, psychiatry, neurology, pharmacology, neuroprotective, metabolic regulation, functional neuromodulation, neurotrophic activity

1. Akai F., Hiruma S., Sato T., Iwamoto N., Fuji-moto M., Ioku M. and Hashimoto S. Neurotrophic factor-like effect of FPF1070 on septal cholinergic neurons after transections of fimbria-fornix in the rat brain. - Histol Histopathol. - 1992. - Vol. 7. - P. 213-221.

2. Alvarez X.A., Cacabelos R., Laredo M., Couceiro V., Sampedro C., Varela M., Corzo L., Fernandez-Novoa L., Vargas M., Aleixandre M., Linares C., Granizo E., Muresanu D. and Moessler H. A 24-week, doubleblind, placebo-controlled study of three dosages of Cerebrolysin in patients with mild to moderate Alzheimer’s disease. - Eur J Neurol. - 2006. - Vol. 3. - P. 43-54.

3. Alvarez X.A., Lombardi V.R., Corzo L., Perez P., Pichel V., Laredo M., Hernandez A., Freixeiro F., Sampedro C., Lorenzo R., Alcaraz M., Windisch M. and Cacabelos R. [2000]. Oral Cerebrolysin enhances brain alpha activity and improves cognitive performance in elderly control subjects. - J Neural Transm Suppl. - 2000. - Vol. 59. - P. 315-328.

4. Alvarez X.A., Lombardi V.R., Fernandez-Novoa L., Garcia M., Sampedro C., Cagiao A., Cacabelos R. and Windisch M. Cerebrolysin reduces microglial activation in vivo and in vitro: a potential mechanism of neuroprotection. J Neural Transm Suppl. - 2000. - Vol. 59 - P. 281-292.

5. Babenkova I.V., Teselkin Iu O., Makashova N.V. and Guseva M.R. [Antioxidative activity of histo-chrome and some other drugs used in ophthalmology]. Vestn Oftalmol. - 1999.- Vol. 115.-P. 22-24.

6. Baskys A. and Wojtowicz J.M. Effects of brain tissue hydrolysate on synaptic transmission in the hippocampus. Pharmacol Biochem Behav.- 1994. Vol. 49. - P. 1105-1107.

7. Bayer E. [Therapy with the cerebral hydrolysate cerebrolysin. A practice report]. Med Welt. - 1980. - Vol. 31. - P. 636-637.

8. Belokrylov G.A. and Malchanova I.V. [Levamin and cerebrolysin as immunostimulants]. Biull Eksp Biol Med. - 1992.- Vol. 113. - P. 165-166.

9. Bespalova M.A., Kliaich K., Maksimova S.P., Chaeva L.S. and Mukhina A.P. [The characteristics of the brain cerebrosides, sulfocerebrosides and gan-gliosides in experimental demyelination and cerebrolysin administration]. Nerv Sist.- 1991.- Vol. 30. - P. 64-71.

10. Boado R.J. Brain-derived peptides regulate the steady state levels and increase stability of the blood-brain barrier GLUT1 glucose transporter mRNA. Neurosci Lett. - 1995. - Vol. 197. - P. 179182.

11. Boado R.J. Brain-derived peptides increase the expression of a blood-brain barrier GLUT1 glucose transporter reporter gene. Neurosci Lett-1996. - Vol. 220. - P. 53-56.

12. Boado R.J. Brain-derived peptides increase blood-brain barrier GLUT1 glucose transporter gene expression via mRNA stabilization. Neurosci Lett. - 1998. - Vol. 255. - P. 147-150.

13. Boado R.J. Post-transcription modulation of the blood-brain barrier GLUT1 glucose transporter by brain-derived factors. J Neural Transm Suppl. - 2000. - Vol. 59. - P. 255-261.

14. Boado R.J. Amplification of blood-brain barrier GLUT1 glucose transporter gene expression by brain-derived peptides. Neurosci Res. - 2001. - Vol. 40. - P. 337-342.

15. Boado R.J., Wu D. and Windisch M. In vivo upregu-lation of the blood-brain barrier GLUT1 glucose transporter by brain-derived peptides. Neurosci Res. - 1999. - Vol. 34. - P. 217-224.

16. Bulon V.V., Kuznetsova N.N., Selina E.N., Kovalenko A.L., Alekseeva L.E. and Sapronov N.S. Neuroprotective effect of cytoflavin during compression injury of the spinal cord. Bull Exp Biol Med. - 2005. - Vol. 139. - P.- 394-396.

17. Bures J., Koroleva V.I., Korolev O.S. and Mares V. [Shifts in the constant potential in the structures of the rat brain in focal ischemia and systemic hypoxia]. Zh Vyssh Nerv Deiat Im I P Pavlova. - 998 -Vol. 48. - P. 640-653.

18. Buresh Y., Koroleva V.I., Korolev O.S. and Maresh V. Changes in the constant potential in brain structures in rats during focal ischemia and systemic hypoxia. Neurosci Behav Physiol. - 1999. - Vol. 29. - P. 569-579.

19. Crook T.H., Ferris S.H., Alvarez X.A., Laredo M. and Moessler H. Effects of N-PEP-12 on memory among older adults. Int Clin Psychopharmacol.- 2005. - Vol. 20. - P. 97-100.

20. Cruz R., Francis L., Diaz-Suarez C.M. and Gonzalez-Fraguela M.E. [Short-term effects of septohippocampal pathway transsection and cerebrolysin effects on glutathione-related enzymes in the rat brain]. Rev Neurol. - 1998. - Vol. 26. - P. 551-554.

21. Deigner H.P., Haberkorn U. and Kinscherf R. Apoptosis modulators in the therapy of neurodegenerative diseases. Expert Opin Investig Drugs. -2000. - Vol. 9. - P. 747-764.

22. Domzal T. and Zaleska B. [Cerebrolysin in treatment of acute ischemic stroke]. Neurol Neurochir Pol. - 1995. - Vol. 29. - P. 325-331.

23. Eder P., Reinprecht I., Schreiner E., Skofitsch G. and Windisch M. Increased density of glutamate receptor subunit 1 due to Cerebrolysin treatment: an immunohistochemical study on aged rats. Histochem J. - 2001. - Vol. 33. - P. 605-612.

24. Francis-Turner L. and Valouskova V. 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. - 1996. - Vol. 202. - P. 193-196.

25. Francis-Turner L., Valouskova V. and Mokry J. The long-term Cerebrolysin Review - Wise Young -Page 25 effect of NGF, b-FGF and Cerebrolysin on the spatial memory after fimbria-fornix lesion in rats. J Neural Transm Suppl. - 1996. - Vol. 47 - P 277.

26. Gannushkina I.V., Antelava A.L. and Baranchikova M.V. [Effect of the nootropic agent cerebrolysin in cerebral ischemia in rats with varying behavioral reactions in the open field test]. Patol Fiziol Eksp Ter. - 1998. - P. 3-8.

27. Gavrilova S.I., Kolykhalov I.V., Korovaitseva G.I., Zharikov G.A., Kalyn Ia B. and Selezneva N.D. [ApoE genotype and efficacy of neurotrophic and cholinergic therapy in Alzheimer’s disease]. Zh Nevrol Psikhiatr Im S S Korsakova. - 2005. - Vol. 105. - P. 27-34.

28. Gershman R.N. and Vasilenko M.A. [Use of cerebrolysin and ATP in treating infantile cerebral paralysis]. Pediatr Akus Ginekol. - 1975. - P. 22-23.

29. Gomazkov O.A. [Apoptosis in neuronal structures and the role of neurotrophic growth factors. Biochemical mechanisms of brain derived peptide preparations]. Zh Nevrol Psikhiatr Im S.S. Korsakova. - 2002. - P. 17-21.

30. Gorbachevskaya N, Bashina V, Gratchev V and Iznak A [2001]. Cerebrolysin therapy in Rett syndrome: clinical and EEG mapping study. Brain Dev. 23 Suppl 1:S90-3.

31. Grechko A.T. [The neurotropic activity of peptide immunomodulators]. Eksp Klin Farmakol. - 1998. - Vol. 61. - P. 14-16.

32. Gromova O.A., Kudrin A.V, Kataev S.I., Mazina S.S. and Volkov A. [Effects of cerebrolysin on trace element homeostasis in the brain]. Zh Nevrol Psikhiatr Im S.S. Korsakova. - 2003.- Vol. 103. - P. 59-61.

33. Grundman M., Corey-Bloom J. and Thal L.J. Perspectives in clinical Alzheimer’s disease research and the development of Cerebrolysin Review - Wise Young - Page 19 antidementia drugs. J Neural Transm Suppl. - 1998. - Vol. 53. - P. 255-275.

34. Gschanes A. and Windisch M. The influence of Cerebrolysin and E021 on spatial navigation of young rats. J Neural Transm Suppl. - 1996. - Vol. 47. - P. 278.

35. Gschanes A. and Windisch M. Early postnatal treatment with peptide preparations influences spatial navigation of young and adult rats. Behav Brain Res. - 1999. - Vol. 100. - P. 161-166.

36. Gschanes A., Boado R., Sametz W. and Windisch M. The drug cerebrolysin and its peptide fraction E021 increase the abundance of the blood-brain barrier GLUT1 glucose transporter in brains of young and old rats. Histochem J. - 2000. - Vol. 32. - P. 71-77.

37. Gusev E.I., Burd G.S., Gekht A.B., Skvortsova V.I., Bogomolova M.A., Selikhova M.V. and Fidler S.M. [The clinico-neurophysiological study of the effect of cerebrolysin on brain function in the acute and early recovery periods of hemispheric ischemic stroke]. Zh Nevropatol Psikhiatr Im S.S. Korsakova. - 1994. - Vol. 94. - P. 9-13.

38. Guseva M.R. and Dubovsakia L.A. [The efficiency of the use of cerebrolysin in optic nerve diseases in children of different age]. Vestn Oftalmol. - 2005. - Vol. 121. - P. 17-20.

39. Gutmann B., Hutter-Paier B., Skofitsch G., Windisch M. and Gmeinbauer R. In vitro models of brain ischemia: the peptidergic drug cerebrolysin protects cultured chick cortical neurons from cell death. Neurotox Res. - 2002. - Vol. 4. - P. 59-65.

40. Haninec P., Dubovy P., Samal F., Houstava L. and Stejskal L. Reinnervation of the rat musculocutaneous nerve stump after its direct reconnection with the C5 spinal cord segment by the nerve graft following avulsion of the ventral spinal roots: a comparison of intrathecal administration of brain-derived neurotrophic factor and Cerebrolysin. Exp Brain Res. - 2004. - Vol. 159. - P. 425-432.

41. Haninec P., Houstava L., Stejskal L. and Dubovy P. Rescue of rat spinal motoneurons from avulsion-induced cell death by intrathecal administration of IGF-I and Cerebrolysin. Ann Anat. - 2003. - Vol. 185. - P. 233-238.

42. Hartbauer M., Hutter-Paie B. and Windisch M. Cerebrolysin on the outgrowth and protection of processes of cultured brain neurons. J Neural Transm. - 2001. - Vol. 108. - P. 581-592.

43. Hutter-Paier B., Eggenreich U. and Windisch M. Dosedependent behavioural effects of two proteinfree peptide derivatives on the passive avoidance reaction of rats. Arzneimittelforschung. - 1996. - Vol. 46. - P. 242-246.

44. Hutter-Paier B., Eggenreich U. and Windisch M. Effects of two protein-free peptide derivatives on passive avoidance behaviour of 24-month-old rats. Arzneimittelforschung. - 1996. - Vol. 46. - P. 237-241.

45. Hutter-Paier B., Fruhwirth M., Grygar E. and Windisch M. Cerebrolysin protects neurons from ischemia-induced loss of microtubule-associated protein 2. J Neural Transm Suppl. - 1996. - Vol. 47. - P. 276.

46. Hutter-Paier B., Grygar E. and Windisch M. Death of cultured telencephalon neurons induced by glutamate is reduced by the peptide derivative Cerebrolysin. J Neural Transm Suppl. - 1996. - Vol. 47. - P. 267-273.

47. Hutter-Paier B., Grygar E., Fruhwirth M., Temmel I. and Windisch M. Further evidence that Cerebrolysin protects cortical neurons from neurodegeneration in vitro. J Neural Transm Suppl. - 1998. - Vol. 53. - P. 363-372.

48. Hutter-Paier B., Steiner E. and Windisch M. Cerebrolysin protects isolated cortical neurons from neurodegeneration after brief histotoxic hypoxia. J Neural Transm Suppl. - 1998. - Vol. 53. - P. 351361.

49. Ishchenko M.M. and Ostrovskaia O.S. [The effect of combined drug treatment on rheologic properties of the blood in patients with disordered circulatory encephalopathy]. Vrach Delo. - 1990. - P. 58-60.

50. Kofler B., Erhart C., Erhart P. and Harrer G. [The usefulness of event-related negativity in demonstrating the therapeutic effects of nootropic drugs using cerebrolysin as an example]. EEG EMG Z Elektroenzephalogr Elektromyogr Verwandte Geb. - 1990. - Vol. 21. - P. 145-149.

51. Koppi S. and Barolin G.S. [Hemodilution therapy with neuron metabolism specific therapy in ischemic stroke-encouraging results of a comparative study]. Wien Med Wochenschr. - 1996. - Vol. 146. - P. 41-48.

52. Koroleva V.I., Korolev O.S., Loseva E. and Bures. The effect of MK-801 and of brain-derived polypeptides on the development of ischemic lesion induced by photothrombotic occlusion of the distal middle cerebral artery in rats. Brain Res. - 1998. - Vol. 786. - P. 104-114.

53. Koroleva V.I., Korolev O.S., Mares V., Pastalkova E. and Bures J. Hippocampal damage induced by carbon monoxide poisoning and spreading depression is alleviated by chronic treatment with brain derived polypeptides. Brain Res. - 1999. - Vol. 816. - P. 618-627.

54. Krasnoperova M.G., Bashina V.M., Skvortsov I.A. and Simashkova N.V. [The effect of cerebrolysin on cognitive functions in childhood autism and in Asperger syndrome]. Zh Nevrol Psikhiatr Im S.S. Korsakova. - 2003. - Vol. 103. - P. 15-18.

55. Ladurner G., Kalvach P. and Moessler H. Neuro-protective treatment with cerebrolysin in patients with acute stroke: a randomised controlled trial. J Neural Transm. - 2005. - Vol. 112. - P. 415-428.

56. Lindner G., Grosse G., Matthies H. and Kirsche W. [Effects of brain extract and hydrolysate on nerve tissue in vitro]. Z Mikrosk Anat Forsch. - 1975. - Vol. 89. - P. 815-823.

57. Litvintsev S.V., Shamrei V.K., Reznik A.M. and Arbuzov A.L. [Perspectives on the treatment of organic mental disorders by the use of nootropic agents]. Voen Med Zh. - 2002. - Vol. 323. - P. 59-62.

58. Lombardi V.R., Windisch M., Garcia M. and Cacabelos R. Effects of Cerebrolysin on in vitro primary microglial and astrocyte rat cell cultures. Methods Find Exp Clin Pharmacol. - 1999. - Vol. 21. - P. 331-338.

59. Makarenko A.N., Kositsin N.S., Nazimov I.V., Svinov M.M., Goloborod’ko E.V. and Pasikova N.V. [A comparative study of antistroke activity of the new drug “cerebral” and its fractions in rats]. Eksp Klin Farmakol. - 2005. - Vol. 68. - P. 15-20.

60. Mallory M., Honer W., Hsu L., Johnson R., Rockenstein E. and Masliah E. In vitro synaptotrophic effects of Cerebrolysin in NT2N cells. Acta Neuropathol [Berl]. -1999. - Vol. 97. - P. 437-446.

61. Masliah E., Armasolo F., Veinbergs I., Mallory M. and Samuel W. Cerebrolysin ameliorates performance deficits, and neuronal damage in apo-lipoprotein E-deficient mice. Pharmacol Biochem Behav. - 1999. - Vol. 62. - P. 239-245.

62. Matula C. and Schoeggl A. Cerebral protection before, during and after neurosurgical procedures. Stereotact Funct Neurosurg. - 2000. - Vol. 75. - P. 142-146.

63. Medvecky J., Jassova Z. and Medvecka E. [Findings in treatment with cerebrolysin]. Cesk Psychi-atr. -1982. - Vol. 78. - P. 308-311.

64. Molloy D.W. and Standish T.I. Clinical experience with Cerebrolysin. J Neural Transm Suppl. - 2000. - Vol. 59. - P. 293-300.

65. Mukhamedzhanov N.Z., Kurbanova D.U. and Tashkhodzhaeva Sh I. [The principles of the combined rehabilitation of patients with perinatal encephalopathy and its sequelae]. Vopr Kurortol Fizioter Lech Fiz Kult. - 1992. - P. 24-28.

66. Naidin V.L and Krotkova O.A. [Cerebrolysin electrophoresis in the correction of the mental defects in neurosurgery patients]. Zh Vopr Neirokhir Im N.N. Burdenko. - 1993. - P. 28-30.

67. Nikolov R. Alzheimer’s disease therapy - an update. Drug News Perspect. - 1998. - Vol. 11. - P. 248-255.

68. Panisset M., Gauthier S., Moessler H. and Windisch M. Cerebrolysin in Alzheimer’s disease: a randomized, double-blind, placebo-controlled trial with a neurotrophic agent. J Neural Transm. - 2002. - Vol. 109. - P. 1089-1104.

69. Panteleeva G.P., Bondar V.V., Krasnikova N.I. and Raiushkin V.A. [Cerebrolysin and magnesium-B6 in the treatment of side effects of psychotropic drugs]. Zh Nevrol Psikhiatr Im S.S. Korsakova. - 1999. - Vol. 99. - P. 37-41.

70. Patockova J., Krsiak M., Marhol P. and Tumova E. Cerebrolysin inhibits lipid peroxidation induced by insulin hypoglycemia in the brain and heart of mice. Physiol Res. - 2003. - Vol. 52. - P. 455-460.

71. Reinprecht I., Gschanes A., Windisch M. and Fachbach G. Two peptidergic drugs increase the synaptophysin immunoreactivity in brains of 24-month-old rats. Histochem J. - 1999. - Vol. 31. - P. 395-401.

72. Riley C., Hutter-Paier B., Windisch M., Doppler E., Moessler H. and Wronski R. A peptide preparation protects cells in organotypic brain slices against cell death after glutamate intoxication. J Neural Transm. - 2006. - Vol. 113. - P. 103-110.

73. Rockenstein E., Torrance M., Mante M., Adame A., Paulino A., Rose J.B., Crews L., Moessler H. and Masliah E. Cerebrolysin decreases amyloid-beta production by regulating amyloid protein precursor maturation in a transgenic model of Alzheimer’s disease. J Neurosci Res. - 2006.

74. Roshchina I.F., Gavrilova S.I., Zharikov G.A., Kalyn Ia B., Kolykhalov I.V. and Selezneva N.D. [Neuropsychological evaluation of longterm therapy of Alzheimer’s disease using different cerebrolysin dosages]. Zh Nevrol Psikhiatr Im S.S. Korsakova. - 2005. - Vol. 105. - P. 52-55.

75. Safarova E.R., Shram S.I., Grivennikov I.A. and Myasoedov N.F Trophic effects of nootropic peptide preparations cerebrolysin and semax on cultured rat pheochromocytoma. Bull Exp Biol Med. - 2002. - Vol. 133. - P. 401-403.

76. Satou T., Itoh T., Tamai Y., Ohde H., Anderson A.J. and Hashimoto S. Neurotrophic effects of FPF-1070 [Cerebrolysin] on cultured neurons from chicken embryo dorsal root ganglia, ciliary ganglia, and sympathetic trunks. J Neural Transm. - 2000. - Vol. 107. - P. 1253-1262.

77. Schauer E., Wronski R., Patockova J., Moessler H., Doppler E., Hutter-Paier B. and Windisch M. Neuroprotection of Cerebrolysin in tissue culture models of brain ischemia: post lesion application indicates a wide therapeutic window. J Neural Transm. - 2005.

78. Schwab M., Antonow-Schlorke I., Zwiener U. and Bauer R. Brain-derived peptides reduce the size of cerebral infarction and loss of MAP2 immunoreac-tivity after focal ischemia in rats. J Neural Transm Suppl. - 1998. - Vol. 53. - P. 299-311.

79. Schwab M., Bauer R. and Zwiener U. Physiological effects and brain protection by hypothermia and cerebrolysin after moderate forebrain ischemia in rats. Exp Toxicol Pathol. - 1997. - Vol. 49. - P. 105-116.

80. Sugita Y., Kondo T., Kanazawa A., Itou T. and Mizuno Y. [Protective effect of FPF 1070 [cerebrolysin] on delayed neuronal death in the gerbil-detec-tion of hydroxyl radicals with salicylic acid]. No To Shinkei. - 1993. - Vol. 45. - P. 325-331.

81. Trojanova M., Karasek F., Pruzkova V. and Mourek J. Influence of cerebrolysin[r] on the resistance of rats to anoxia. Physiol Bohemoslov. - 1976. - Vol. 25. - P. 319-323.

82. Valouskova V. and Gschanes A. Effects of NGF, b-FGF, and cerebrolysin on water maze performance and on motor activity of rats: short- and longterm study. Neurobiol Learn Mem. - 1999. - Vol. 71. - P. 132-149.

83. Veinbergs I., Mante M., Mallory M. and Masliah E. Neurotrophic effects of Cerebrolysin in animal models of excitotoxicity. J Neural Transm Suppl. - 2000. - Vol. 59. - P. 273-280.

84. Wenzel J., Stender G. and Duwe G. [Development of neuron structure of the fascia dentata in the rat. Neurohistologicomorphometric, ultrastructural and experimental study]. J Hirnforsch. - 1981. - Vol. 22. - P. 629-683.

85. Windisch M. and Piswanger A. [Modification of rat brain metabolism by long-term treatment with a peptide derivative]. Arzneimittelforschung. - 1985. - Vol. 35. - P. 1353-1356.

86. Wronski R., Kronawetter S., Hutter-Paier B., Crailsheim K. and Windisch M. A brain derived peptide preparation reduces the translation dependent loss of a cytoskeletal protein in primary cultured chicken neurons. J Neural Transm Suppl. - 2000. - Vol. 59. - P. 263-272.

87. Xiong H., Baskys A. and Wojtowicz J.M. Brainderived peptides inhibit synaptic transmission via presynaptic GABAB receptors in CA1 area of rat hippocampal slices. Brain Res. - 1996. - Vol. 737. - P. 188-194.

88. Zemkova H., Kruek J. and Vyskocil F. Potentiation of GABAA receptor in cultured mouse hippocampal cells by brain-derived peptide mixture cerebrolysin. Physiol Res. - 1995. - Vol. 44. - P. 151-155.

89. Zommer K. and Kvandt I. [The effect of brain hydrolysate on central nervous system structure]. Zh Nevropatol Psikhiatr Im S.S. Korsakova. -1975. - Vol. 75. - P. 1021-1025.

90. Zuber V.L. [The effect of cerebrolysin on the metabolism of brain phospholipids in growing animals with experimental demyelination]. Nerv Sist. - 1991. - Vol. 30. - P. 85-90.