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The Effect of Semax and Its C-End Peptide PGP on the Morphology and Proliferative Activity of Rat Brain Cells During Experimental Ischemia: A Pilot Study

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Abstract

The neuropeptide preparation Semax (Met-Glu-His-Phe-Pro-Gly-Pro) has been employed successfully in clinical practice for treating patients with severe brain blood circulation disorders. In spite of numerous studies, many aspects of the therapeutic effects of this preparation remain unknown. In this context, the effects of Semax and its C-end tripeptide PGP on the functional morphology of nervous tissue cells were studied in the normal rat brain and in a model of incomplete global rat brain ischemia. In control animals, both peptides activated the capillary network and caused similar morphological changes to neurons and the neuropil regions. We show here for the first time at the histological level that Semax and PGP increased proliferation of the neuroglia, blood vessel endothelium, and progenitor cells in the subventricular zone. In these experimental conditions, only Semax abated the manifestation of ischemic damage to the nervous tissue. This was probably attributable to a decrease in vascular stasis symptoms as well as the trophic effect of the peptide.

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Abbreviations

ACTH:

Adrenocorticotropic hormone

SVZ:

Subventricular zone

PS:

Physiological saline (0.9% NaCl)

CNS:

Central nervous system

PGP:

Tripeptide Pro-Gly-Pro

PCNA:

Proliferating cell nuclear antigen

SO:

Sham operation

H&E:

Hematoxylin and eosin

References

  • Abrous DN, Koehl M, Le Moal M (2005) Adult neurogenesis: from precursors to network and physiology. Physiol Rev 85:523–569

    Article  PubMed  CAS  Google Scholar 

  • Astashkin EI, Bespalova Yu B, Grivennikov IA et al (2000) Effects of Semax on Ca2+ responses of human neutrophils. Dokl Biol Sci 374:536–538

    PubMed  CAS  Google Scholar 

  • Bashkatova VG, Koshelev VB, Fadyukova OE et al (2001) Novel synthetic analogue of ACTH 4–10 (Semax) but not glycine prevents the enhanced nitric oxide generation in cerebral cortex of rats with incomplete global ischemia. Brain Res 894:145–149

    Article  PubMed  CAS  Google Scholar 

  • Chen XH, Iwata A, Nonaka M, Browne KD, Smith DH (2003) Neurogenesis and glial proliferation persist for at least one year in the subventricular zone following brain trauma in rats. J Neurotrauma 20:623–631

    Article  PubMed  Google Scholar 

  • Cheng YD, Al-Khoury L, Zivin JA (2004) Neuroprotection for ischemic stroke: two decades of success and failure. NeuroRx 1:36–45

    Article  PubMed  Google Scholar 

  • Cherkasova KA, Lyapina LA, Ashmarin IP (2001) Comparative study of modulatory effects of Semax and primary proline-containing peptides on hemostatic reactions. Bull Exp Biol Med 132:625–626

    Article  PubMed  CAS  Google Scholar 

  • Dmitrieva VG, Dergunova LV, Povarova OV, Skvortsova VI, Limborskaya SA, Myasoedov NF (2008) The effect of semax and the C-terminal peptide PGP on expression of growth factor genes and receptors in rats under conditions of experimental cerebral ischemia. Dokl Biochem Biophys 422:261–264

    Article  PubMed  CAS  Google Scholar 

  • Dmitrieva VG, Povarova OV, Skvortsova VI, Limborska SA, Myasoedov NF, Dergunova LV (2010) Semax and Pro-Gly-Pro activate the transcription of neurotrophins and their receptor genes after cerebral ischemia. Cell Mol Neurobiol 30:71–79

    Article  PubMed  CAS  Google Scholar 

  • Dolotov OV, Seredenina TS, Levitskaya NG et al (2003) The heptapeptide SEMAX stimulates BDNF expression in different areas of the rat brain in vivo. Dokl Biol Sci 391:292–295

    Article  PubMed  CAS  Google Scholar 

  • Faiz M, Acarin L, Castellano B, Gonzalez B (2005) Proliferation dynamics of germinative zone cells in the intact and excitotoxically lesioned postnatal rat brain. BMC Neurosci 6:26–42

    Article  PubMed  Google Scholar 

  • Garcia JH, Liu KF, Ho KL (1995) Neuronal necrosis after middle cerebral artery occlusion in Wistar rats progresses at different time intervals in the caudoputamen and the cortex. Stroke 26:636–642

    Article  PubMed  CAS  Google Scholar 

  • Ginsberg MD (2003) Adventures in the pathophysiology of brain ischemia: penumbra, gene expression, neuroprotection. The 2002 Thomas Willis lecture. Stroke 34:214–223

    Article  PubMed  Google Scholar 

  • Grivennikov IA, Dolotov OV, Zolotarev YA et al (2008) Effects of behaviorally active ACTH (4–10) analogue - Semax on rat basal forebrain cholinergic neurons. Restor Neurol Neurosci 26:35–43

    PubMed  CAS  Google Scholar 

  • Gusev Eu I, Skvortsova VI (2001) Brain ischaemia. Meditsina, Moscow, pp 249–276

    Google Scholar 

  • Gusev EI, Skvortsova VI, Chukanova EI (2005) Semax in prevention of disease progress and development of exacerbations in patients with cerebrovascular insufficiency. Zh Nevrol Psikhiatr Im SS Korsakova 105:35–40

    CAS  Google Scholar 

  • Iadecola C (1999) Mechanisms of cerebral ischemic damage. In: Walz W (ed) Cerebral ischemia: molecular and cellular pathophysiology. Humana, New Jersey, pp 3–32

    Google Scholar 

  • Johnson EA, Svetlov SI, Pike BR et al (2004) Cell-specific upregulation of survivin after experimental traumatic brain injury in rats. J Neurotrauma 21:1183–1195

    Article  PubMed  Google Scholar 

  • Kaplan A Ya, Kochetova AG, Nezavibathko VN, Rjasina TV, Ashmarin IP (1996) Synthetic ACTH analogue Semax displays nootropic-like activity in humans. Neurosci Res Commun 19:115–123

    Article  CAS  Google Scholar 

  • Levitskaya NG, Sebentsova EA, Andreeva LA, Alfeeva LY, Kamenskii AA, Myasoedov NF (2004) The neuroprotective effects of Semax in conditions of MPTP-induced lesions of the brain dopaminergic system. Neurosci Behav Physiol 34:399–405

    Article  PubMed  CAS  Google Scholar 

  • Li Y, Powers C, Jiang N, Chopp M (1998) Intact, injured, necrotic and apoptotic cells after focal cerebral ischemia in the rat. J Neurol Sci 156:119–132

    Article  PubMed  CAS  Google Scholar 

  • Lipton P (1999) Ischemic cell death in brain neurons. Physiol Rev 79:1431–1568

    PubMed  CAS  Google Scholar 

  • Martynova KV, Andreeva LA, Klimova PA et al (2009) Structural-functional study of glycine-and-proline-containing peptides (glyprolines) as potential neuroprotectors. Bioorg Khim 35:165–171

    PubMed  CAS  Google Scholar 

  • Paxinos G, Watson C (1997) The rat brain in stereotaxic coordinates. Compact, 3rd edn. Acadamic, San Diego

    Google Scholar 

  • Polunin GS, Nurieva SM, Baiandin DL, Sheremet NL, Andreeva LA (2000) Evaluation of therapeutic effect of new Russian drug semax in optic nerve disease. Vestn Oftalmol 116:15–18

    PubMed  CAS  Google Scholar 

  • Shadrina MI, Dolotov OV, Grivennikov IA et al (2001) Rapid induction of neurotrophin mRNA in rat cell culteres by Semax, an adrenocorticotropic hormone analog. Neurosci Lett 308:115–118

    Article  PubMed  CAS  Google Scholar 

  • Storozhevykh TP, Tukhbatova GR, Senilova YE, Pinelis VG, Andreeva LA, Myasoyedov NF (2007) Effects of semax and its Pro-Gly-Pro fragment on calcium homeostasis of neurons and their survival under conditions of glutamate toxicity. Bull Exp Biol Med 143:601–604

    Article  PubMed  CAS  Google Scholar 

  • Strand FL (1999) New vistas for melanocortins. Finally, an explanation for their pleiotropic functions. Ann NY Acad Sci 897:1–16

    Article  PubMed  CAS  Google Scholar 

  • Tsyb AF, Yuzhakov VV, Roshal' LM et al (2009) Morphofunctional study of the therapeutic efficacy of human mesenchymal and neural stem cells in rats with diffuse brain injury. Bull Exp Biol Med 147:132–146

    Article  PubMed  CAS  Google Scholar 

  • Umriukhin PE, Koplik EV, Grivennikov IA, Miasoedov NF, Sudakov KV (2001) Gene c-Fos expression in brain of rats resistant and predisposed to emotional stress after intraperitoneal injection of the ACTH (4–10) analog—Semax. Zh Vyssh Nerv Deiat Im I P Pavlova 51:220–227

    PubMed  CAS  Google Scholar 

  • Yakovleva EV, Kuzenkov VS, Fedorov VN et al (1999) In vivo efficiency of semax in global cerebral ischemia. Bull Exp Biol Med 128:172–174

    Article  Google Scholar 

  • Yakovlev AG, Faden AI (2004) Mechanisms of neural cell death: implications for development of neuroprotective treatment strategies. NeuroRx 1:5–16

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This study was partially supported by grants of the Russian Foundation for Basic Research (08-04-01279), the “Molecular and Cell Biology” Program of the Russian Academy of Sciences, and the Federal Program for Support of Scientific Schools of the Russian Ministry of Science and Education.

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Authors and Affiliations

  1. Human Molecular Genetics Department, Institute of Molecular Genetics of the Russian Academy of Sciences, 123182 Kurchatov sq., 2, Moscow, Russia

    Vasily V. Stavchansky, Svetlana A. Limborska, Nikolay F. Myasoedov & Lyudmila V. Dergunova

  2. Medical Radiological Research Center, RAMS, Obninsk, Russia

    Vadim V. Yuzhakov, Lyubov N. Bondurko & Marina G. Tsyganova

  3. Institute of Brain Stroke, Russian State Medical University, Moscow, Russia

    Alexandra Yu. Botsina, Veronika I. Skvortsova, Svetlana A. Limborska & Lyudmila V. Dergunova

Authors
  1. Vasily V. Stavchansky
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  2. Vadim V. Yuzhakov
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  3. Alexandra Yu. Botsina
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  4. Veronika I. Skvortsova
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  5. Lyubov N. Bondurko
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  6. Marina G. Tsyganova
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  7. Svetlana A. Limborska
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  8. Nikolay F. Myasoedov
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  9. Lyudmila V. Dergunova
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Correspondence to Vasily V. Stavchansky.

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Stavchansky, V.V., Yuzhakov, V.V., Botsina, A.Y. et al. The Effect of Semax and Its C-End Peptide PGP on the Morphology and Proliferative Activity of Rat Brain Cells During Experimental Ischemia: A Pilot Study. J Mol Neurosci 45, 177–185 (2011). https://doi.org/10.1007/s12031-010-9421-2

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  • DOI: https://doi.org/10.1007/s12031-010-9421-2

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