The pharmacology of neurotrophic treatment with cerebrolysin: Brain protection and repair to counteract pathologies of acute and chronic neurological disorders

Drugs of Today

Volumn 48, Issue SUPPL. A, 2012, Pages 3-24

  Masliah, E ^a   Diez Tejedor E ^b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSIDAD AUTÓNOMA DE MADRID   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID BETA PROTEIN[1-42]; AMYLOID PRECURSOR PROTEIN; CALPASTATIN; CEREBROLYSIN; GLUTAMIC ACID; MICROTUBULE ASSOCIATED PROTEIN 2; NERVE GROWTH FACTOR; SUPEROXIDE DISMUTASE; SYNAPTOPHYSIN;

ACUTE BRAIN DISEASE; ACUTE DISEASE; ALZHEIMER DISEASE; AMNESIA; BRAIN ISCHEMIA; BRAIN PROTECTION; CHRONIC BRAIN DISEASE; COGNITIVE DEFECT; DEMENTIA; DRUG EFFICACY; DRUG SAFETY; EDEMA; ENZYME ACTIVITY; EXCITOTOXICITY; GLIOSIS; HIPPOCAMPUS; IN VITRO STUDY; IN VIVO STUDY; INFLAMMATION; LEARNING DISORDER; MIDDLE CEREBRAL ARTERY OCCLUSION; NERVE CELL PLASTICITY; NERVE DEGENERATION; NERVE REGENERATION; NEUROFIBRILLARY TANGLE; NEUROLOGIC DISEASE; NEUROPROTECTION; NONHUMAN; PROTEIN PHOSPHORYLATION; REVIEW; SPINAL CORD INJURY; STROKE; TRANSGENIC MOUSE; TRAUMATIC BRAIN INJURY;

ACUTE DISEASE; AMINO ACIDS; ANIMALS; BRAIN; BRAIN INJURIES; BRAIN ISCHEMIA; CELL DEATH; CELL SURVIVAL; CHRONIC DISEASE; HUMANS; NERVE GROWTH FACTORS; NERVE REGENERATION; NERVOUS SYSTEM DISEASES; NEUROPROTECTIVE AGENTS; SPINAL CORD INJURIES;

EID: 84860844706     PISSN: 16993993     EISSN: 16994019     Source Type: Journal    
DOI: 10.1358/dot.2012.48(Suppl.A).1739716     Document Type: Review

References (70)

1. Bornstein, N., Poon, W.S. Accelerated recovery from acute brain injuries: clinical efficacy of neurotrophic treatment in stroke and traumatic brain injuries. Drugs Today 2012, 48(Suppl. A): 43-61.
2. Allegri, R.F., Guekht, A. Cerebrolysin improves symptoms and delays progression in patients with Alzheimer's disease and vascular dementia. Drugs Today 2012, 48(Suppl. A): 25-41.
3. EVER Neuro Pharma GmbH, Summary of Product Characteristics, March 2009.
4. Windholz, E., Gschanes, A., Windisch, M., Fachbach, G. Two peptidergic drugs increase the synaptophysin immunoreactivity in brains of 6-week-old rats. Histochem J 2000, 32(2): 79-84. (Pubitemid 30224396)
5. Veinbergs, I., Mante, M., Mallory, M., Masliah, E. Neurotrophic effects of Cerebrolysin in animal models of excitotoxicity. J Neural Transm Suppl 2000, 59: 273-80. (Pubitemid 30479427)
6. Hartbauer, M., Hutter-Paier, B., Skofitsch, G., Windisch, M. Antiapoptotic effects of the peptidergic drug cerebrolysin on primary cultures of embryonic chick cortical neurons. J Neural Transm 2001, 108(4): 459-73. (Pubitemid 32703895)
7. Rockenstein, E., Mante, M., Adame, A., Crews, L., Moessler, H., Masliah, E. Effects of Cerebrolysin on neurogenesis in an APP transgenic model of Alzheimer's disease. Acta Neuropathol 2007, 113(3): 265-75. (Pubitemid 46443562)
8. Thome, J., Doppler, E. Safety profile of Cerebrolysin: clinical experience from dementia and stroke trials. Drugs Today 2012, 48(Suppl. A): 63-9.
9. Hutter-Paier, B., Eggenreich, U., Windisch, M. Effects of two protein-free peptide derivatives on passive avoidance behaviour of 24-month-old rats. Arzneimittelforschung 1996, 46(3): 237-41. (Pubitemid 26111136)
10. Hutter-Paier, B., Grygar, E., Fruhwirth, M., Temmel, I., Windisch, M. Further evidence that Cerebrolysin protects cortical neurons from neurodegeneration in vitro. J Neural Transm Suppl 1998, 53: 363-72. (Pubitemid 28361795)
11. Gonzalez, M.E., Francis, L., Castellano, O. Antioxidant systemic effect of short-term Cerebrolysin administration. J Neural Transm Suppl 1998, 53: 333-41. (Pubitemid 28361792)
12. Sugita, Y., Kondo, T., Kanazawa, A., Itou, T., Mizuno, Y. [Protective effect of FPF 1070 (cerebrolysin) on delayed neuronal death in the gerbil-detection of hydroxyl radicals with salicylic acid]. No To Shinkei 1993, 45(4): 325-31. (Pubitemid 23181400)
13. Lombardi, V.R., Windisch, M., Garcia, M., Cacabelos, R. Effects of Cerebrolysin on in vitro primary microglial and astrocyte rat cell cultures. Methods Find Exp Clin Pharmacol 1999, 21(5): 331-8. (Pubitemid 29291248)
14. Alvarez, X.A., Lombardi, V.R., Fernandez-Novoa, L. et al. Cerebrolysin reduces microglial activation in vivo and in vitro: a potential mechanism of neuroprotection. J Neural Transm Suppl 2000, 59: 281-92. (Pubitemid 30479428)
15. Wolf, H.J., Hutter-Paie, B., Gmeinbauer, R., Windisch, M. Serum withdrawal induced apoptosis in embryonic chicken cortical neurons in vitro, protection with neurotrophic peptides preparation. 5th Int Conf Prog Alzheimer Parkinson Dis (March 31-April 5, Kyoto) 2001.
16. Akai, F., Hiruma, S., Sato, T., Iwamoto, N., Fujimoto, M., Ioku, M., Hashimoto, S. Neurotrophic factor-like effect of FPF1070 on septal cholinergic neurons after transections of fimbriafornix in the rat brain. Histol Histopathol 1992, 7(2): 213-21.
17. Francis-Turner, L., Valouskova, V. Nerve growth factor and nootropic drug Cerebrolysin but not fibroblast growth factor can reduce spatial memory impairment elicited by fimbriafornix transection: short-term study. Neurosci Lett 1996, 202(3): 193-6. (Pubitemid 26029834)
18. Valouskova, V., Gschanes, A. Effects of NGF, b-FGF, and cerebrolysin on water maze performance and on motor activity of rats: short- and long-term study. Neurobiol Learn Mem 1999, 71(2): 132-49. (Pubitemid 29397965)
19. Hutter-Paier, B., Steiner, E., Windisch, M. Cerebrolysin protects isolated cortical neurons from neurodegeneration after brief histotoxic hypoxia. J Neural Transm Suppl 1998, 53: 351-61. (Pubitemid 28361794)
20. Schwab, M., Antonow-Schlorke, I., Durer, U., Bauer, R. Effects of Cerebrolysin on cytoskeletal proteins after focal ischemia in rats. J Neural Transm Suppl 1996, 47: 279. (Pubitemid 26275610)
21. Wronski, R., Tompa, P., Hutter-Paier, B., Crailsheim, K., Friedrich, P., Windisch, M. Inhibitory effect of a brain derived peptide preparation on the Ca++-dependent protease, calpain. J Neural Transm 2000, 107(2): 145-57. (Pubitemid 30095366)
22. Vantini, G. The pharmacological potential of neurotrophins: a perspective. Psychoneuroendocrinology 1992, 17(4): 401-10.
23. Yuen, E.C., Howe, C.L., Li, Y., Holtzman, D.M., Mobley, W.C. Nerve growth factor and the neurotrophic factor hypothesis. Brain Dev 1996, 18(5): 362-8. (Pubitemid 26336372)
24. Satou, T., Itoh, T., Tamai, Y., Ohde, H., Anderson, A.J., 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, 107(11): 1253-62.
25. Masliah, E., Armasolo, F., Veinbergs, I., Mallory, M., Samuel, W. Cerebrolysin ameliorates performance deficits, and neuronal damage in apolipoprotein E-deficient mice. Pharmacol Biochem Behav 1999, 62(2): 239-45. (Pubitemid 29070887)
26. Masliah, E., Mallory, M., Alford, M., DeTeresa, R., Iwai, A., Saitoh, T. Molecular mechanisms of synaptic disconnection in Alzheimer's disease. In: Connections, Cognition and Alzheimer's Disease. B.T. Hyman, C. Duyckaerts, Y. Christen (Eds.). Springer: Berlin, Heidelberg, New York, Tokyo 1997, 121-40.
27. Gschanes, A., Windisch, M. Early postnatal treatment with peptide preparations influences spatial navigation of young and adult rats. Behav Brain Res 1999, 100(1-2): 161-6. (Pubitemid 29130250)
28. Valouskova, V., Francis-Turner, L. Can Cerebrolysin influence chronic deterioration of spatial learning and memory? J Neural Transm Suppl 1998, 53: 343-9. (Pubitemid 28361793)
29. Masliah, E., Rockenstein, E. Genetically altered transgenic models of Alzheimer's disease. J Neural Transm Suppl 2000, 59: 175-83. (Pubitemid 30479418)
30. Rockenstein, E., Mallory, M., Mante, M., Alford, M., Windisch, M., Moessler, H., Masliah, E. Effects of Cerebrolysin on amyloid- beta deposition in a transgenic model of Alzheimer's disease. J Neural Transm Suppl 2002(62): 327-36. (Pubitemid 37046677)
31. Rockenstein, E., Adame, A., Mante, M., Moessler, H., Windisch, M., Masliah, E. The neuroprotective effects of Cerebrolysin in a transgenic model of Alzheimer's disease are associated with improved behavioral performance. J Neural Transm 2003, 110(11): 1313-27. (Pubitemid 37500752)
32. Reinprecht, I., Gschanes, A., Windisch, M., Fachbach, G. Two peptidergic drugs increase the synaptophysin immunoreactivity in brains of 24-month-old rats. Histochem J 1999, 31(6): 395-401. (Pubitemid 29362823)
33. Gschanes, A., Windisch, M. The influence of Cerebrolysin and E021 on spatial navigation of 24-month-old rats. J Neural Transm Suppl 1998, 53: 313-21. (Pubitemid 28361790)
34. Mallory, M., Honer, W., Hsu, L., Johnson, R., Rockenstein, E., Masliah, E. In vitro synaptotrophic effects of Cerebrolysin in NT2N cells. Acta Neuropathol 1999, 97(5): 437-46. (Pubitemid 29195106)
35. Biebl, M., Cooper, C.M., Winkler, J., Kuhn, H.G. Analysis of neurogenesis and programmed cell death reveals a selfrenewing capacity in the adult rat brain. Neurosci Lett 2000, 291(1): 17-20. (Pubitemid 30658102)
36. Stopa, E.G., Gonzalez, A.M., Chorsky, R., Corona, R.J., Alvarez, J., Bird, E.D., Baird, A. Basic fibroblast growth factor in Alzheimer's disease. Biochem Biophys Res Commun 1990, 171(2): 690-6. (Pubitemid 20289439)
37. Magavi, S.S., Leavitt, B.R., Macklis, J.D. Induction of neurogenesis in the neocortex of adult mice. Nature 2000, 405(6789): 951-5. (Pubitemid 30435051)
38. Wen, Y., Yang, S.H., Liu, R., Perez, E.J., Brun-Zinkernagel, A.M., Koulen, P., Simpkins, J.W. Cdk5 is involved in NFT-like tauopathy induced by transient cerebral ischemia in female rats. Biochim Biophys Acta 2007, 1772(4): 473-83. (Pubitemid 46400382)
39. Dong, H., Goico, B., Martin, M., Csernansky, C.A., Bertchume, A., Csernansky, J.G. Modulation of hippocampal cell proliferation, memory, and amyloid plaque deposition in APPsw (Tg2576) mutant mice by isolation stress. Neuroscience 2004, 127(3): 601-9. (Pubitemid 38993164)
40. Donovan, M.H., Yazdani, U., Norris, R.D., Games, D., German, D.C., Eisch, A.J. Decreased adult hippocampal neurogenesis in the PDAPP mouse model of Alzheimer's disease. J Comp Neurol 2006, 495(1): 70-83. (Pubitemid 43238052)
41. van Praag, H., Schinder, A.F., Christie, B.R., Toni, N., Palmer, T.D., Gage, F.H. Functional neurogenesis in the adult hippocampus. Nature 2002, 415(6875): 1030-4. (Pubitemid 34193451)
42. Tatebayashi, Y., Lee, M.H., Li, L., Iqbal, K., Grundke-Iqbal, I. The dentate gyrus neurogenesis: a therapeutic target for Alzheimer's disease. Acta Neuropathol 2003, 105(3): 225-32. (Pubitemid 36798813)
43. Cummings, B.J., Su, J.H., Cotman, C.W. Neuritic involvement within bFGF immunopositive plaques of Alzheimer's disease. Exp Neurol 1993, 124(2): 315-25. (Pubitemid 24041779)
44. Chen, H., Tung, Y.C., Li, B., Iqbal, K., Grundke-Iqbal, I. Trophic factors counteract elevated FGF-2-induced inhibition of adult neurogenesis. Neurobiol Aging 2007, 28(8): 1148-62. (Pubitemid 46810057)
45. Zhang, C., Chopp, M., Cui, Y., et al. Cerebrolysin enhances neurogenesis in the ischemic brain and improves functional outcome after stroke. J Neurosci Res 2010, 88(15): 3275-81.
46. Wallace, J.E., Krauter, E.E., Campbell, B.A. Animal-models of declining memory in the aged: short-term and spatial memory in the aged rat. J Gerontol 1980, 35(3): 355-63. (Pubitemid 10100581)
47. Gold, P.E. The use of avoidance training in studies of modulation of memory storage. Behav Neural Biol 1986, 46(1): 87-98.
48. Rockenstein, E., Ubhi, K., Pham, E. et al. Beneficial effects ofa neurotrophic peptidergic mixture persist for a prolonged period following treatment interruption in a transgenic model of Alzheimer's disease. J Neurosci Res 2011, 89(11): 1812-21.
49. Rockenstein, E., Torrance, M., Mante, M. et al. Cerebrolysin decreases amyloid-beta production by regulating amyloid protein precursor maturation in a transgenic model of Alzheimer's disease. J Neurosci Res 2006, 83(7): 1252-61. (Pubitemid 43668008)
50. Ubhi, K., Rockenstein, E., Doppler, E. et al. Neurofibrillary and neurodegenerative pathology in APP-transgenic mice injected with AAV2-mutant TAU: neuroprotective effects of Cerebrolysin. Acta Neuropathol 2009, 117(6): 699-712.
51. Gotz, J., Chen, F., van Dorpe, J., Nitsch, R.M. Formation of neurofibrillary tangles in P301l tau transgenic mice induced by Abeta 42 fibrils. Science 2001, 293(5534): 1491-5. (Pubitemid 32807681)
52. Mattson, M.P. Apoptotic and anti-apoptotic synaptic signaling mechanisms. Brain Pathol 2000, 10(2): 300-12. (Pubitemid 30181099)
53. Revesz, T., Holton, J.L., Lashley, T., Plant, G., Rostagno, A., Ghiso, J., Frangione, B. Sporadic and familial cerebral amyloid angiopathies. Brain Pathol 2002, 12(3): 343-57. (Pubitemid 34743217)
54. Rockenstein, E., Adame, A., Mante, M. et al. Amelioration of the cerebrovascular amyloidosis in a transgenic model of Alzheimer's disease with the neurotrophic compound cerebrolysin. J Neural Transm 2005, 112(2): 269-82. (Pubitemid 40179119)
55. Bowes, M. Neurotrophic factors, and foibles, in stroke research. Neurologyreviews.com 2000, 8(12).
56. Gutmann, B., Hutter-Paier, B., Skofitsch, G., Windisch, M., Gmeinbauer, R. In vitro models of brain ischemia: the peptidergic drug cerebrolysin protects cultured chick cortical neurons from cell death. Neurotox Res 2002, 4(1): 59-65. (Pubitemid 34285046)
57. Riley, C., Hutter-Paier, B., Windisch, M., Doppler, E.,Moessler, H., Wronski, R. A peptide preparation protects cells in organotypic brain slices against cell death after glutamate intoxication. J Neural Transm 2006, 113(1): 103-10. (Pubitemid 41828961)
58. Merino, J.J., Gutierrez, M., Alvarez Grech, J., Rodriguez, B., Gonzalez, G., de Miguel, E., Diez Tejedor, E. Brain porcine neuropeptide (cerebrolysin) modulates stromal cell derivate alpha 1 proinflammatory chemokine in stroke and prevents apoptosis staurosporine induced by decreasing CXCR4 chemokine levels in neuroblastoma N2A cell line. Cephalalgia 2009, 29(1, Suppl.): 60-1.
59. Schauer, E., Wronski, R., Patockova, J., Moessler, H., Doppler, E., Hutter-Paier, B., Windisch, M. Neuroprotection of cerebrolysin in tissue culture models of brain ischemia: post lesion application indicates a wide therapeutic window. J Neural Transm 2006, 113(7): 855-68. (Pubitemid 43964814)
60. Sacchetti, B., Lorenzini, C.A., Baldi, E., Bucherelli, C., Roberto, M., Tassoni, G., Brunelli, M. Pituitary adenylate cyclase-activating polypeptide hormone (PACAP) at very low dosages improves memory in the rat. Neurobiol Learn Mem 2001, 76(1): 1-6. (Pubitemid 32566145)
61. Mamounas, L.A., Altar, C.A., Blue, M.E., Kaplan, D.R., Tessarollo, L., Lyons, W.E. BDNF promotes the regenerative sprouting, but not survival, of injured serotonergic axons in the adult rat brain. J Neurosci 2000, 20(2): 771-82. (Pubitemid 30225579)
62. Schwab, M., Bauer, R., Zwiener, U. Physiological effects and brain protection by hypothermia and cerebrolysin after moderate forebrain ischemia in rats. Exp Toxicol Pathol 1997, 49(1-2): 105-16. (Pubitemid 27113356)
63. Schwab, M., Schaller, R., Bauer, R., Zwiener, U. Morphofunctional effects of moderate forebrain ischemia combined with short-term hypoxia in rats-protective effects of Cerebrolysin. Exp Toxicol Pathol 1997, 49(1-2): 29-37. (Pubitemid 27113343)
64. Hanson, L.R., Liu, X.F., Ross, T.M., Doppler, E., Zimmermann-Meinzingen, S., Moessler, H., Frey II, W.H. Cerebrolysin reduces infarct volume in a rat model of focal cerebral ischemic damage. Am J Neuroprotec Neuroregen 2009, 1(1): 60-6.
65. Schwab, M., Antonow-Schlorke, I., Zwiener, U., Bauer, R. Brain-derived peptides reduce the size of cerebral infarction and loss of MAP2 immunoreactivity after focal ischemia in rats. J Neural Transm Suppl 1998, 53: 299-311. (Pubitemid 28361789)
66. Ren, J., Sietsma, D., Qiu, S., Moessler, H., Finklestein, S.P. Cerebrolysin enhances functional recovery following focal cerebral infarction in rats. Restor Neurol Neurosci 2007, 25(1): 25-31. (Pubitemid 46631011)
67. Conte, V., Royo, N., Shimizu, S. et al. Neurotrophic factors: Pathophysiology and therapeutic applications in traumatic brain injury. Eur J Trauma 2003, 29(6): 335-55. (Pubitemid 38055542)
68. Abdelaziz, O., Elbanna, Y.M., Elnaggar, A.M., Mourad, C.M. Effects of neuropeptide derivate FPF 1070 (cerebrolysin) administration on experimental acute spinal cord injury. Pan Arab J Neurosurg 2007, 11: 51-61.
69. Haninec, P., Houst'ava, L., Stejskal, L., Dubovy, P. Rescue of rat spinal motoneurons from avulsion-induced cell death by intrathecal administration of IGF-I and Cerebrolysin. Ann Anat 2003, 185(3): 233-8. (Pubitemid 36700680)
70. Haninec, P., Dubovy, P., Samal, F., Houstava, L., 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, 159(4): 425-32. (Pubitemid 40064284)