Skip to main content

Advertisement

SpringerLink
Log in

Neuroprotection of Cerebrolysin in tissue culture models of brain ischemia: post lesion application indicates a wide therapeutic window

  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Summary.

All attempts to reduce neuronal damage after acute brain ischemia by the use of neuroprotective compounds have failed to prove efficacy in clinical trials so far. One of the main reasons might be the relatively narrow time window for intervention. In this study 2 different tissue culture models of ischemia, excitotoxic lesion by the use of glutamate and oxygen–glucose deprivation (OGD), were used to investigate the effects of delayed application of Cerebrolysin (Cere) on neuronal survival. This drug consists of low molecular weight peptides with neuroprotective and neurotrophic properties similar to naturally occurring growth factors. After both types of lesion, acute as well as delayed treatment with Cere resulted in a dose dependent and significant rescue of neurons. In the model of excitotoxic cell death significant drug effects were found even when the treatment started with a delay of 96 hours after addition of glutamate. In the OGD model pronounced effects were found after 48 hours delay of treatment, and even after 72 hours a small but significant rescue of neurons was detected. The neuroprotective effects of a single addition of Cerebrolysin to the culture medium resulted in significant protection until end of the experiments which was up to 2 weeks after the initial lesion. A shift of the efficacious dosages from low to high concentrations indicates that most likely active compounds are used up, indicating that multiple dosing might even increase the effect size. In conclusion the results indicate that Cere displays a relatively wide therapeutic time window which might be explained by a combination of acute neuroprotective properties and neurotrophic efficacy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • H Abboud P Amarenco (2004) ArticleTitleThrombolysis and acute stroke MS-Med Sci 20 1104–1108

    Google Scholar 

  • GE Abdelkarim K Gertz C Harms J Katchanov U Dirnagl C Szabó M Endres (2001) ArticleTitleProtective effects of PJ34, a novel, potent inhibitor of poly (ADP-ribose) polymerase (PARP) in in vitro and in vivo models of stroke Int J Mol Med 7 255–260 Occurrence Handle11179503 Occurrence Handle1:CAS:528:DC%2BD3MXhsFCrtrs%3D

    PubMed  CAS  Google Scholar 

  • K Abe (2000) ArticleTitleTherapeutic potential of neurotrophic factors and neural stem cells against ischemic brain injury J Cerebr Blood F Met 20 1393–1408 Occurrence Handle1:CAS:528:DC%2BD3cXnsF2ns7w%3D Occurrence Handle10.1097/00004647-200010000-00001

    Article  CAS  Google Scholar 

  • S Abu-Raya R Tabakman E Blaugrund V Trembovler P Lazarovici (2002) ArticleTitleNeuroprotective and neurotoxic effects of monoamine oxidase-B inhibitors and derived metabolites under ischemia in PC12 cells Eur J Pharmacol 434 109–116 Occurrence Handle11779573 Occurrence Handle1:CAS:528:DC%2BD38XltFSq Occurrence Handle10.1016/S0014-2999(01)01548-5

    Article  PubMed  CAS  Google Scholar 

  • HP Adams (2001) ArticleTitleTreatment of acute ischemic stroke: selecting the right treatment for the right patient Eur Neurol 45 61–66 Occurrence Handle11244267 Occurrence Handle1:CAS:528:DC%2BD3MXhvFentLk%3D Occurrence Handle10.1159/000052097

    Article  PubMed  CAS  Google Scholar 

  • N Ahmed P Näsman NG Wahlgren (2000) ArticleTitleEffect of intravenous nimodipine on blood pressure and outcome after acute stroke Stroke 31 1250–1255 Occurrence Handle10835440 Occurrence Handle1:CAS:528:DC%2BD3cXkt1Cntr8%3D

    PubMed  CAS  Google Scholar 

  • S Ashwell (2001) ArticleTitleCaspases: recent advances in small molecule inhibitors Expert Opin Ther Pat 11 1593–1603 Occurrence Handle1:CAS:528:DC%2BD3MXnsFOjsLY%3D Occurrence Handle10.1517/13543776.11.10.1593

    Article  CAS  Google Scholar 

  • T Back (1998) ArticleTitlePathophysiology of the ischemic penumbra – revision of a concept Cell Mol Neurobiol 18 621–638 Occurrence Handle9876870 Occurrence Handle1:STN:280:DyaK1M%2FpsVWmsg%3D%3D Occurrence Handle10.1023/A:1020265701407

    Article  PubMed  CAS  Google Scholar 

  • T Back OG Schuler (2004) ArticleTitleThe natural course of lesion development in brain ischemia Acta Neurochir 89 55–61 Occurrence Handle1:STN:280:DC%2BD2cvivFOltw%3D%3D

    CAS  Google Scholar 

  • WF Baker (2005) ArticleTitleThrombolytic therapy: current clinical practice Hematol Oncol Clin N 19 147–181 Occurrence Handle10.1016/j.hoc.2004.09.008

    Article  Google Scholar 

  • GS Barolin S Koppi E Kapeller (1996) ArticleTitleOld and new aspects of stroke treatment with emphasis on metabolically active medication and rehabilitative outcome Euro Rehab 3 135–143

    Google Scholar 

  • S Bastianetto WH Zheng R Quirion (2000) ArticleTitleThe Ginkgo biloba extract (EGb 761) protects and rescues hippocampal cells against nitric oxide-induced toxicity: involvement of its flavonoid constituents and protein kinase C J Neurochem 74 2268–2277 Occurrence Handle10820186 Occurrence Handle1:CAS:528:DC%2BD3cXjsVKku7o%3D Occurrence Handle10.1046/j.1471-4159.2000.0742268.x

    Article  PubMed  CAS  Google Scholar 

  • A Bethel JR Kirsch RC Koehler SP Finklestein RJ Traystman (1997) ArticleTitleIntravenous basic fibroblast growth factor decreases brain injury resulting from focal ischemia in cats Stroke 28 609–616 Occurrence Handle9056620 Occurrence Handle1:CAS:528:DyaK2sXitVyhu7Y%3D

    PubMed  CAS  Google Scholar 

  • P Calabresi D Centonze LM Cupini C Costa F Pisani G Bernardi (2003) ArticleTitleIonotropic glutamate receptors: still a target for neuroprotection in brain ischemia? Insights from in vitro studies Neurobiol Dis 12 82–88 Occurrence Handle12609492 Occurrence Handle1:CAS:528:DC%2BD3sXhsVajtrg%3D Occurrence Handle10.1016/S0969-9961(02)00016-5

    Article  PubMed  CAS  Google Scholar 

  • K Chandrasekaran Z Mehrabian B Spinnewyn C Chinopoulos K Drieu G Fiskum (2003) ArticleTitleNeuroprotective effects of bilobalide, a component of Ginkgo biloba extract (EGb 761(R)) in global brain ischemia and in excitotoxicity-induced neuronal death Pharmacopsychiatry 36 S89–S94 Occurrence Handle13130395 Occurrence Handle1:CAS:528:DC%2BD3sXnvVSlt78%3D

    PubMed  CAS  Google Scholar 

  • A Chiarugi E Meli M Calvani R Picca R Baronti E Camaioni G Costantino M Marinozzi DE Pellegrini-Giampietro R Pellicciari F Moroni (2003) ArticleTitleNovel isoquinolinone-derived inhibitors of poly(ADP-ribose) polymerase-1: pharmacological characterization and neuroprotective effects in an in vitro model of cerebral ischemia J Pharmacol Exp Ther 305 943–949 Occurrence Handle12606624 Occurrence Handle1:CAS:528:DC%2BD3sXkt1SnsLY%3D Occurrence Handle10.1124/jpet.103.048934

    Article  PubMed  CAS  Google Scholar 

  • E Ciani L Groneng M Voltattorni V Rolseth A Contestabile RE Paulsen (1996) ArticleTitleInhibition of free radical production of free radical scavenging protects from the excitotoxic cell death medicated by glutamate in cultures of cerebellar granule neurons Brain Res 728 1–6 Occurrence Handle8864290 Occurrence Handle1:CAS:528:DyaK28XkslCks7c%3D Occurrence Handle10.1016/0006-8993(96)00382-4

    Article  PubMed  CAS  Google Scholar 

  • D Corbett S Nurse (1998) ArticleTitleThe problem of assessing effective neuroprotection in experimental cerebral ischemia Prog Neurobiol 54 531–548 Occurrence Handle9550190 Occurrence Handle1:CAS:528:DyaK1cXitlymt78%3D Occurrence Handle10.1016/S0301-0082(97)00078-6

    Article  PubMed  CAS  Google Scholar 

  • P Cuevas (1997) ArticleTitleTherapeutic prospects for fibroblast growth factor treatment of brain ischemia Neurol Res 19 355–356 Occurrence Handle9263212 Occurrence Handle1:CAS:528:DyaK2sXlvFGjtLw%3D

    PubMed  CAS  Google Scholar 

  • MA deLeciñana E Díez-Tejedor F Carcller JM Roda (2001) ArticleTitleCerebral ischemia: from animal studies to clinical practice. Should the methods be reviewed? Cerebrovasc Dis 11 20–30

    Google Scholar 

  • G Devuyst J Bogousslavsky (2001) ArticleTitleRecent progress in drug treatment for acute ischemic stroke Cerebrovasc Dis 11 71–79 Occurrence Handle11244203 Occurrence Handle1:CAS:528:DC%2BD3MXisVGlt74%3D Occurrence Handle10.1159/000049128

    Article  PubMed  CAS  Google Scholar 

  • J Ekblom H Garpenstrand O Tottmar JA Prince (1998) ArticleTitleA cell culture model of cerebral ischemia as a convenient system to screen for neuroprotective drugs J Neural Transm 52 93–98 Occurrence Handle1:CAS:528:DyaK1cXjtlSjtro%3D

    CAS  Google Scholar 

  • I Ferrer J Ballabriga E Marti E Perez J Alberch E Arenas (1998) ArticleTitleBDNF up-regulates TrkB protein and prevents the death of CA1 neurons following transient forebrain ischemia Brain Pathol 8 253–261 Occurrence Handle9546284 Occurrence Handle1:CAS:528:DyaK1cXjslKhsrg%3D

    PubMed  CAS  Google Scholar 

  • I Ferrer J Krupinski E Goutan E Martí S Ambrosio E Arenas (2001) ArticleTitleBrain-derived neurotrophic factor reduces cortical cell death by ischemia after middle cerebral artery occlusion in the rat Acta Neuropathol 101 229–238 Occurrence Handle11307622 Occurrence Handle1:CAS:528:DC%2BD3MXht1ejs7g%3D

    PubMed  CAS  Google Scholar 

  • M Fisher R Ratan (2003) ArticleTitleNew perspectives on developing acute stroke therapy Ann Neurol 53 10–20 Occurrence Handle12509843 Occurrence Handle10.1002/ana.10407

    Article  PubMed  Google Scholar 

  • GW Glazner F Boland AE Dresse DE Brennemann I Gozes MP Mattson (1999) ArticleTitleActivity-dependent neurotrophic factor peptide (ADNF9) protects neurons against oxidative stress-induced death J Neurochem 73 2341–2347 Occurrence Handle10582592 Occurrence Handle1:CAS:528:DyaK1MXns1ehur4%3D Occurrence Handle10.1046/j.1471-4159.1999.0732341.x

    Article  PubMed  CAS  Google Scholar 

  • LB Goldstein (2004) ArticleTitleNeuroprotective therapy for acute ischaemic stroke: down, but not out Lancet 363 414–415 Occurrence Handle14962518 Occurrence Handle10.1016/S0140-6736(04)15522-0

    Article  PubMed  Google Scholar 

  • I Gozes DE Brenneman (2000) ArticleTitleA new concept in the pharmacology of neuroprotection J Mol Neurosci 14 61–68 Occurrence Handle10854037 Occurrence Handle1:CAS:528:DC%2BD3cXjvFWnurg%3D Occurrence Handle10.1385/JMN:14:1-2:061

    Article  PubMed  CAS  Google Scholar 

  • JC Grotta WS Burgin A El Mitwalli M Long M Campbell LB Morgenstern M Malkoff AV Alexandrov (2001) ArticleTitleIntravenous tissue-type plasminogen activator therapy for ischemic stroke – Houston experience 1996 to 2000 Arch Neurol 58 2009–2013 Occurrence Handle11735774 Occurrence Handle1:STN:280:DC%2BD38%2FivVyrsQ%3D%3D Occurrence Handle10.1001/archneur.58.12.2009

    Article  PubMed  CAS  Google Scholar 

  • A Gschanes V Valouskova M Windisch (1997) ArticleTitleAmeliorative influence of a nootropic drug on motor activity of rats after bilateral carotid artery occlusion J Neural Transm 104 1319–1327 Occurrence Handle9503278 Occurrence Handle1:CAS:528:DyaK1cXhtlOlsLo%3D Occurrence Handle10.1007/BF01294733

    Article  PubMed  CAS  Google Scholar 

  • ZH Guo MP Mattson (2000) ArticleTitleNeurotrophic factors protect cortical synaptic terminals against amyloid- and oxidative stress-induced impairment of glucose transport, glutamate transport and mitochondrial function Cereb Cortex 10 50–57 Occurrence Handle10639395 Occurrence Handle1:CAS:528:DC%2BD3cXhvFalt7g%3D Occurrence Handle10.1093/cercor/10.1.50

    Article  PubMed  CAS  Google Scholar 

  • B Gutmann B Hutter-Paier G Skofitsch M Windisch R Gmeinbauer (2002) ArticleTitleIn vitro models of brain ischemia: the peptidergic drug cerebrolysin protects cultured chick cortical neurons from cell death Neurotox Res 4 59–65 Occurrence Handle12826494 Occurrence Handle1:CAS:528:DC%2BD38Xmsl2jur4%3D Occurrence Handle10.1080/10298420290007637

    Article  PubMed  CAS  Google Scholar 

  • M Hartbauer B Hutter-Paier G Skofitsch M Windisch (2001a) ArticleTitleAntiapoptotic effects of the peptidergic drug Cerebrolysin on primary cultures of embryonic chick cortical neurons J Neural Transm 108 459–473 Occurrence Handle1:CAS:528:DC%2BD3MXltFGksr4%3D Occurrence Handle10.1007/s007020170067

    Article  CAS  Google Scholar 

  • M Hartbauer B Hutter-Paier M Windisch (2001b) ArticleTitleEffects of Cerebrolysin on the outgrowth and protection of processes of cultured brain neurons J Neural Transm 108 581–592 Occurrence Handle1:CAS:528:DC%2BD3MXlvVKhtrw%3D Occurrence Handle10.1007/s007020170058

    Article  CAS  Google Scholar 

  • M Holcik H Gibson RG Korneluk (2001) ArticleTitleXIAP: apoptotic brake and promising therapeutic target Apoptosis 6 253–261 Occurrence Handle11445667 Occurrence Handle1:CAS:528:DC%2BD3MXmsF2qu7g%3D Occurrence Handle10.1023/A:1011379307472

    Article  PubMed  CAS  Google Scholar 

  • XL Hu IM Johansson T Brännström T Olsson P Wester (2002) ArticleTitleLong-lasting neuronal apoptotic cell death in regions with severe ischemia after photothrombotic ring stroke in rats Acta Neuropathol 104 462–470 Occurrence Handle12410394 Occurrence Handle1:CAS:528:DC%2BD38XnsFOltL4%3D

    PubMed  CAS  Google Scholar 

  • B Hutter-Paier E Grygar M Loibner G Skofitsch M Windisch (2000) ArticleTitleEffects of NaCN and ionomycin on neuronal viability and on the abundance of microtubule-associated proteins MAP1, MAP2, and tau in isolated chick cortical neurons Cell Tissue Res 302 39–47 Occurrence Handle11079714 Occurrence Handle1:CAS:528:DC%2BD3cXnvVKktLw%3D Occurrence Handle10.1007/s004410000258

    Article  PubMed  CAS  Google Scholar 

  • B Hutter-Paier E Grygar M Windisch (1996) ArticleTitleDeath of cultured telencephalon neurons induced by glutamate is reduced by the peptide derivative Cerebrolysin J Neural Transm 47 267–273 Occurrence Handle1:CAS:528:DyaK28XlvFKms7Y%3D

    CAS  Google Scholar 

  • B Hutter-Paier E Steiner M Windisch (1998) ArticleTitleCerebrolysin protects isolated cortical neurons from neurodegeneration after brief histotoxic hypoxia J Neural Transm 53 351–361 Occurrence Handle1:CAS:528:DyaK1cXmvVWntLo%3D

    CAS  Google Scholar 

  • K Jin XO Mao SP Batteur E McEachron A Leahy DA Greenberg (2001) ArticleTitleCaspase-3 and the regulation of hypoxic neuronal death by vascular endothelial growth factor Neuroscience 108 351–358 Occurrence Handle11734367 Occurrence Handle1:CAS:528:DC%2BD3MXovVelu74%3D Occurrence Handle10.1016/S0306-4522(01)00154-3

    Article  PubMed  CAS  Google Scholar 

  • KL Jin XO Mao DA Greenberg (2000) ArticleTitleVascular endothelial growth factor: direct neuroprotective effect in in vitro ischemia PNAS 97 10242–10247 Occurrence Handle10963684 Occurrence Handle1:CAS:528:DC%2BD3cXmtleht7c%3D Occurrence Handle10.1073/pnas.97.18.10242

    Article  PubMed  CAS  Google Scholar 

  • DA Kaku M Goldberg D Choi (1991) ArticleTitleAntagonism of non-NMDA receptors augments the neuroprotective effect of NMDA receptor blockade in cortical cultures subjected to prolonged deprivation of oxygen and glucose Brain Res 554 344–347 Occurrence Handle1681989 Occurrence Handle1:CAS:528:DyaK3MXltVKrtbY%3D Occurrence Handle10.1016/0006-8993(91)90214-G

    Article  PubMed  CAS  Google Scholar 

  • KK Katsuta H Nakanishi K Shirakawa K Yoshida K Takagi A Tamura (1995) ArticleTitleThe neuroprotective effect of the novel non competitive NMDA antagonist, FR115427 in focal cerebral ischemia in rats J Cereb Blood Flow Metab 15 345–348 Occurrence Handle7860668 Occurrence Handle1:CAS:528:DyaK2MXktlymsr4%3D

    PubMed  CAS  Google Scholar 

  • T Kobayashi Y Mori (1998) ArticleTitleCa2+ channel antagonists and neuroprotection from cerebral ischemia Eur J Pharmacol 363 1–15 Occurrence Handle9877076 Occurrence Handle1:CAS:528:DyaK1cXotFWjtLw%3D Occurrence Handle10.1016/S0014-2999(98)00774-2

    Article  PubMed  CAS  Google Scholar 

  • J Krieglstein (1997) ArticleTitleExcitotoxicity and neuroprotection Eur J Pharm Sci 5 181–187 Occurrence Handle1:CAS:528:DyaK2sXkvFOis70%3D Occurrence Handle10.1016/S0928-0987(97)00276-5

    Article  CAS  Google Scholar 

  • M Kusumoto E Dux KA Hossmann (1997) ArticleTitleEffect of trophic factors on delayed neuronal death induced by in vitro ischemia in cultivated hippocampal and cortical neurons Metab Brain Dis 12 113–120 Occurrence Handle9203156 Occurrence Handle1:CAS:528:DyaK2sXkslCrsr8%3D Occurrence Handle10.1023/B:MEBR.0000007106.51802.37

    Article  PubMed  CAS  Google Scholar 

  • G Ladurner (2001) ArticleTitleNeuroprotection in acute ischaemic stroke Stroke 32 1

    Google Scholar 

  • G Ladurner P Kalvach H Moessler (2005) ArticleTitleNeuroprotective treatment with Cerebrolysin in patients with acute stroke: a randomised controlled trial J Neural Transm 112 415–428 Occurrence Handle15583955 Occurrence Handle1:CAS:528:DC%2BD2MXhsVOmtrg%3D Occurrence Handle10.1007/s00702-004-0248-2

    Article  PubMed  CAS  Google Scholar 

  • W Lee C Bondy (1991) ArticleTitleInsulin-like growth factors and cerebral ischemia Ann NY Acad Sci 1993 418–422

    Google Scholar 

  • AS Lesage KL De Loore L Peeters Je Leyesen (1995) ArticleTitleNeuroprotective sigma ligands interfere with the glutamate-activated NOS pathway in hippocampal cell culture Synapse 20 156–164 Occurrence Handle7570346 Occurrence Handle1:CAS:528:DyaK2MXmtVegtLw%3D Occurrence Handle10.1002/syn.890200210

    Article  PubMed  CAS  Google Scholar 

  • DS Liebeskind SE Kasner (2001) ArticleTitleNeuroprotection for ischaemic stroke – an unattainable goal? CNS Drugs 15 165–174 Occurrence Handle11463125 Occurrence Handle1:CAS:528:DC%2BD3MXislyktLY%3D Occurrence Handle10.2165/00023210-200115030-00001

    Article  PubMed  CAS  Google Scholar 

  • JG Mielke YT Wang (2005) ArticleTitleInsulin exerts neuroprotection by counteracting the decrease in cell-surface GABA(A) receptors following oxygen–glucose deprivation in cultured cortical neurons J Neurochem 92 103–113 Occurrence Handle15606900 Occurrence Handle1:CAS:528:DC%2BD2MXivFyrtQ%3D%3D Occurrence Handle10.1111/j.1471-4159.2004.02841.x

    Article  PubMed  CAS  Google Scholar 

  • G Mouw JL Zechel Y Zhou WD Lust WR Selman RA Ratcheson (2002) ArticleTitleCaspase-9 inhibition after focal cerebral ischemia improves outcome following reversible focal ischemia Metab Brain Dis 17 143–151 Occurrence Handle12322785 Occurrence Handle1:CAS:528:DC%2BD38XmsVGlsr8%3D Occurrence Handle10.1023/A:1019921904378

    Article  PubMed  CAS  Google Scholar 

  • M Nakazawa K Matsuno S Mita (1998) ArticleTitleActivation of sigma(1) receptor subtype leads to neuroprotection in the rat primary neuronal cultures Neurochem Int 32 337–343 Occurrence Handle9596556 Occurrence Handle1:CAS:528:DyaK1cXivV2hsbw%3D Occurrence Handle10.1016/S0197-0186(97)00105-8

    Article  PubMed  CAS  Google Scholar 

  • B Pettmann J Louis M Sensenbrenner (1979) ArticleTitleMorphological and biochemical maturation of neurones cultured in the absence of glial cells Nature 281 378–380 Occurrence Handle39256 Occurrence Handle1:STN:280:Bi%2BD3M7ms1I%3D

    PubMed  CAS  Google Scholar 

  • Piswanger A, Paier B, Windisch M (1990) Modulation of protein synthesis in a cell-free system from rat brain by Cerebrolysin during development and aging. In: Amino acids: chemistry, biology and medicine. Escom, Leiden, pp 651–657

  • LO Porciúncula JBT Rocha CR Boeck D Vendite DO Souza (2001) ArticleTitleEbselen prevents excitotoxicity provoked by glutamate in rat cerebellar granule neurons Neurosci Lett 299 217–220 Occurrence Handle11165774 Occurrence Handle10.1016/S0304-3940(01)01519-1

    Article  PubMed  Google Scholar 

  • K Prass U Dirnagl (1998) ArticleTitleGlutamate antagonists in therapy of stroke Restor Neurol Neuros 13 3–10 Occurrence Handle1:CAS:528:DyaK1cXotFSnsrs%3D

    CAS  Google Scholar 

  • T Rootwelt M Dunn M Yudkoff T Itoh R Almaas D Pleasure (1998) ArticleTitleHypoxic cell death in human NT2-N neurons: involvement of NMDA and non-NMDA glutamate receptors J Neurochem 71 1544–1553 Occurrence Handle9751188 Occurrence Handle1:CAS:528:DyaK1cXmt1Kitrg%3D

    PubMed  CAS  Google Scholar 

  • T Satou T Itoh Y Tamai H Ohde AJ Anderson S Hashimoto (2000) ArticleTitleNeurotrophic effects of FPF-1070 (Cerebrolysin) on cultured neurons from chicken embryo dorsal root ganglia, ciliary ganglia, and sympathetic trunks J Neural Transm 107 1253–1262 Occurrence Handle11145001 Occurrence Handle1:CAS:528:DC%2BD3MXhtlGrsL0%3D Occurrence Handle10.1007/s007020070015

    Article  PubMed  CAS  Google Scholar 

  • PD Schellinger M Kaste W Hacke (2004) ArticleTitleAn update on thrombolytic therapy for acute stroke Curr Opin Neurol 17 69–77 Occurrence Handle15090880 Occurrence Handle1:CAS:528:DC%2BD2cXislylu74%3D Occurrence Handle10.1097/00019052-200402000-00012

    Article  PubMed  CAS  Google Scholar 

  • M Schwab I Antonow-Schlorke U Zwiener R Bauer (1998) ArticleTitleBrain-derived peptides reduce the size of cerebral infarction and loss of MAP2 immunoreactivity after focal ischemia in rats J Neural Transm 53 299–311 Occurrence Handle1:CAS:528:DyaK1cXmvVWnt7c%3D

    CAS  Google Scholar 

  • M Schwab R Schaller R Bauer U Zwiener (1997) ArticleTitleMorphofunctional effects of moderate forebrain ischemia combined with short-term hypoxia in rats – protective effects of Cerebrolysin Exp Toxicol Pathol 49 29–37 Occurrence Handle9085071 Occurrence Handle1:CAS:528:DyaK2sXhvFGhtrg%3D

    PubMed  CAS  Google Scholar 

  • VE Shashoua DS Adams A Boyer-Boiteau A Cornell-Bell FH Li M Fisher (2003) ArticleTitleNeuroprotective effects of a new synthetic peptide, CMX-9236, in in vitro and in vivo models of cerebral ischemia Brain Res 963 214–223 Occurrence Handle12560127 Occurrence Handle1:CAS:528:DC%2BD3sXmsV2hug%3D%3D Occurrence Handle10.1016/S0006-8993(02)04058-1

    Article  PubMed  CAS  Google Scholar 

  • T Shimazaki (2003) ArticleTitleBiology and clinical application of neural stem cells Horm Res 60 1–9 Occurrence Handle14671388 Occurrence Handle1:CAS:528:DC%2BD3sXps12htro%3D Occurrence Handle10.1159/000074492

    Article  PubMed  CAS  Google Scholar 

  • K Shoge HK Mishima T Saitoh K Ishihara Y Tamura H Shiomi M Sasa (1998) ArticleTitleProtective effects of vasoactive intestinal peptide against delayed glutamate neurotoxicity in cultured retina Brain Res 809 127–136 Occurrence Handle9795184 Occurrence Handle1:CAS:528:DyaK1cXms1Sqsr8%3D Occurrence Handle10.1016/S0006-8993(98)00789-6

    Article  PubMed  CAS  Google Scholar 

  • E Sigalov M Fridkin DE Brenneman I Gozes (2000) ArticleTitleVIP-related protection against iodoacetate toxicity in pheochromocytoma (PC12) cells J Mol Neurosci 15 147–154 Occurrence Handle11303779 Occurrence Handle1:CAS:528:DC%2BD3MXisFKqsLs%3D Occurrence Handle10.1385/JMN:15:3:147

    Article  PubMed  CAS  Google Scholar 

  • Y Sugita T Kondo A Kanazawa T Itou Y Mizuno (1993) ArticleTitleProtective effect of FPF (Cerebrolysin) on delayed neuronal death in the gerbil – detection of hydroxyl radicals with salicylic acid Brain Nerve 45 325–331 Occurrence Handle8334017 Occurrence Handle1:CAS:528:DyaK3sXkvVGrtrY%3D

    PubMed  CAS  Google Scholar 

  • AY Sun JH Cheng (1999) ArticleTitleNovel targets for therapeutic intervention against ischemic brain injury Clin Neuropharmacol 22 164–171 Occurrence Handle10367181 Occurrence Handle1:CAS:528:DyaK1MXjvFOnsbY%3D

    PubMed  CAS  Google Scholar 

  • JJ Svoboda (2005) ArticleTitleThrombolysis for acute stroke JAMA 293 421–422 Occurrence Handle15671422 Occurrence Handle1:CAS:528:DC%2BD2MXntFGltg%3D%3D Occurrence Handle10.1001/jama.293.4.421-c

    Article  PubMed  CAS  Google Scholar 

  • Y Tatebayashi MH Lee L LI K Iqbal I Grundke-Iqbal (2003) ArticleTitleThe dentate gyrus neurogenesis: a therapeutic target for Alzheimer’s disease Acta Neuropathol 105 225–232 Occurrence Handle12557008 Occurrence Handle1:CAS:528:DC%2BD3sXntV2iuw%3D%3D

    PubMed  CAS  Google Scholar 

  • K Unoki M Lavail (1994) ArticleTitleProtection of the rat retina from ischemic injury by brain-derived neurotrophic factor, ciliary neurotrophic factor, and basic fibroblast growth factor Invest Ophtalmol Vis Sci 35 907–915 Occurrence Handle1:STN:280:ByuC2s7lt1Y%3D

    CAS  Google Scholar 

  • JJ Vornov RC Tasker JT Coyle (1994) ArticleTitleDelayed protection by MK-801 and tetrodotoxin in a rat organotypic hippocampal culture model of ischemia Stroke 25 457–465 Occurrence Handle8303757 Occurrence Handle1:CAS:528:DyaK2cXivV2qt7s%3D

    PubMed  CAS  Google Scholar 

  • NG Wahlgren N Ahmed (2004) ArticleTitleNeuroprotection in cerebral ischaemia: facts and fancies – the need for new approaches Cerebrovasc Dis 17 153–166 Occurrence Handle14694293 Occurrence Handle1:CAS:528:DC%2BD3sXhtVSqsrfK Occurrence Handle10.1159/000074808

    Article  PubMed  CAS  Google Scholar 

  • PC Waldmeier (2003) ArticleTitleProspects for antiapoptotic drug therapy of neurodegenerative diseases Prog Neuropsychopath 27 303–321 Occurrence Handle1:CAS:528:DC%2BD3sXit12ntrc%3D Occurrence Handle10.1016/S0278-5846(03)00025-3

    Article  CAS  Google Scholar 

  • JM Wardlaw PAG Sandercock E Berge (2003) ArticleTitleThrombolytic therapy with recombinant tissue plasminogen activator for acute ischemic stroke – where do we go from here? A cumulative meta-analysis Stroke 34 1437–1442 Occurrence Handle12730560 Occurrence Handle1:CAS:528:DC%2BD3sXktVKmsrw%3D Occurrence Handle10.1161/01.STR.0000072513.72262.7E

    Article  PubMed  CAS  Google Scholar 

  • C Wiessner D Sauer D Alaimo PR Allegrini (2000) ArticleTitleProtective effect of a caspase inhibitor in models for cerebral ischemia in vitro and in vivo Cell Mol Biol 46 53–62 Occurrence Handle10726971 Occurrence Handle1:CAS:528:DC%2BD3cXhvFShs7g%3D

    PubMed  CAS  Google Scholar 

  • M Windisch E Albrecht U Eggenreich B Paier (1993) ArticleTitleNeurotrophic effects of the nootropic drug Cerebrolysin – a summary Adv Biosci 87 355–356 Occurrence Handle1:CAS:528:DyaK3sXlvFGgsbs%3D

    CAS  Google Scholar 

  • M Windisch A Gschanes B Hutter-Paier (1998) ArticleTitleNeurotrophic activities and therapeutic experience with a brain derived peptide preparation J Neural Transm 53 289–298 Occurrence Handle1:CAS:528:DyaK1cXmvVWnt7Y%3D

    CAS  Google Scholar 

  • R Wronski P Tompa B Hutter-Paier K Crailsheim P Friedrich M Windisch (2000) ArticleTitleInhibitory effect of a brain derived peptide preparation on the Ca++-dependent protease, calpain J Neural Transm 107 145–157 Occurrence Handle10847556 Occurrence Handle1:CAS:528:DC%2BD3cXisFeqtL8%3D Occurrence Handle10.1007/s007020050013

    Article  PubMed  CAS  Google Scholar 

  • MBH Youdim O BarAm M Yogev-Falach O Weinreb W Maruyama M Naoi T Amit (2005) ArticleTitleRasagiline: neurodegeneration, neuroprotection, and mitochondrial permeability transition J Neurosci Res 79 172–179 Occurrence Handle15573406 Occurrence Handle1:CAS:528:DC%2BD2MXltlCltA%3D%3D Occurrence Handle10.1002/jnr.20350

    Article  PubMed  CAS  Google Scholar 

  • JH Zhang GG Haddad Y Xia (2000) ArticleTitled-, but not m- and kappa-, opioid receptor activation protects neocortical neurons from glutamate-induced excitotoxic injury Brain Res 885 143–153 Occurrence Handle11102568 Occurrence Handle1:CAS:528:DC%2BD3cXotlCqs7w%3D Occurrence Handle10.1016/S0006-8993(00)02906-1

    Article  PubMed  CAS  Google Scholar 

  • ZG Zhang L Zhang M Yepes Q Jiang QJ Li P Arniego TA Coleman DA Lawrence M Chopp (2002) ArticleTitleAdjuvant treatment with neuroserpin increases the therapeutic window for tissue-type plasminogen activator administration in a rat model of embolic stroke Circulation 106 740–745 Occurrence Handle12163437 Occurrence Handle1:CAS:528:DC%2BD38XmvFSmsLo%3D

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. JSW-Research, Institute of Experimental Pharmacology, Graz, Austria

    E. Schauer, R. Wronski, B. Hutter-Paier & M. Windisch

  2. Department of Pharmacology, 3rd Faculty of Medicine, Charles University, Praha, Czech Republic

    J. Patockova

  3. EBEWE Pharma, Unterach, Austria

    H. Moessler & E. Doppler

Authors
  1. E. Schauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Wronski
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Patockova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H. Moessler
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. E. Doppler
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. B. Hutter-Paier
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M. Windisch
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schauer, E., Wronski, R., Patockova, J. et al. Neuroprotection of Cerebrolysin in tissue culture models of brain ischemia: post lesion application indicates a wide therapeutic window. J Neural Transm 113, 855–868 (2006). https://doi.org/10.1007/s00702-005-0384-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-005-0384-3

Search

Navigation