Skip to main content
SpringerLink
Log in

Towards a New Paradigm in Neuroprotection and Neuroplasticity

  • Chapter
  • First Online:
Brain Protection in Schizophrenia, Mood and Cognitive Disorders

Abstract

Neurologists are confronted with more and more new information regarding the intimate processes taking place in both the normal and pathological brain. This chapter briefly reviews some of the mechanisms involved in the pathogenesis of neurological diseases and the ways to bind them with therapy principles. It is becoming increasingly clear that using neuroprotective molecules with only one mechanism of action is a utopian idea. It is still not easy to find the correct therapeutic approach for neurological disorders, especially because we do not deeply understand all endogenous basic biological processes, the complete nature of pathophysiological processes and the links between these two categories. In particular, concepts like neurotrophicity, neuroprotection, neuroplasticity, neurogenesis and anoikis, as well as their clinical utility, may be daunting. Even more specifically, there are many points in the pathophysiological cascade where pharmacological intervention might be beneficial. Comprehensive research of multimodal drugs and combination therapy, followed by appropriate clinical use, should be encouraged. Although the majority of scientific data available in the present chapter are referring mainly to vascular and neurodegenerative disorders, they can be easily extrapolated to other different pathologies.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

ATP:

Adenosine-5'-triphosphate

DNA:

Deoxyribonucleic acid

ACD:

active cell death

PCD:

passive cell death

EDA:

endogenous defense activity

PI3K:

(phosphoinositide 3-kinase) Akt

Ras–ERK1/2:

extra cellular-signal-regulated kinase 1/2

CREB:

CRE (cAMP-response element)-binding protein

NMDA:

N-methyl-D-aspartic acid

NMDAR:

NMDA receptor

TRPM:

transient receptor potential melastatin channel

CaMKIV:

Calcium/calmodulin-dependent protein kinase type IV

ERK1/2:

Extracellular Signal-Regulated Kinases 1 and 2

PI3K:

Phosphoinositide 3-kinases

nNOS:

neuronal nitric oxide synthase

TRPM:

transient receptor potential melastatin channel

BBB:

blood–brain barrier

CNS:

central nervous system

References

  1. Sloviter R. Apoptosis: a guide for perplexed. Trends Pharmacol Sci 2002; 23:19–24

    Article  CAS  PubMed  Google Scholar 

  2. Kalivas PW, Volkow ND. The neural basis of addiction: pathology of motivation and choice. Am J Psychiatry 2005; 162:1403–1413

    Article  PubMed  Google Scholar 

  3. Muresanu DF. Neurotrophic factors. Bucuresti: Libripress; 2003

    Google Scholar 

  4. Muresanu FD. Neuroprotection and neuroplasticity – a holistic approach and future perspectives. J Neurol Sci 2007; 257:38–43

    Article  PubMed  Google Scholar 

  5. Hawkins BT, Davis TP. The blood-brain barrier/neurovascular unit in health and disease. Pharmacol Rev 2005; 57:173–185

    Article  CAS  PubMed  Google Scholar 

  6. Frisch SM, Screaton RA. Anoikis mechanisms. Curr Opin Cell Biol, 2001; 13(5):555–562

    Article  CAS  PubMed  Google Scholar 

  7. Wu HY, Yuen EY, Lu YF, et al. Regulation of N-Methyl-D-aspartate receptors by calpain in cortical neurons. J Biol Chem 2005; 280:21588–21593

    Article  CAS  PubMed  Google Scholar 

  8. 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; 53:363–372

    Article  CAS  PubMed  Google Scholar 

  9. Hetman M, Kharebava G. Survival signaling pathways activated by NMDA receptors. Curr Top Med Chem 2006; 6:787–799

    Article  CAS  PubMed  Google Scholar 

  10. Brunet A, Datta SR, Greenberg M.E. Transcription-dependent and -independent control of neuronal survival by the PI3K-Akt signaling pathway. Curr Opin Neurobiol 2001; 11:297–305

    Article  CAS  PubMed  Google Scholar 

  11. Hardingham GE, Arnold FJ, Bading H. A calcium microdomain near NMDA receptors: on switch for ERK-dependent synapse-tonucleus communication. Nat Neurosci 2001; 4:565–566

    Article  CAS  PubMed  Google Scholar 

  12. Hardingham GE, Fukunaga Y, Bading H. Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways. Nat Neurosci 2002; 5:405–414

    CAS  PubMed  Google Scholar 

  13. Arundine M, Tymianski M. Molecular mechanisms of glutamate-dependent neurodegeneration in ischemia and traumatic brain injury. Cell Mol Life Sci 2004; 61:657–668

    Article  CAS  PubMed  Google Scholar 

  14. Bano D, Young KW, Guerin CJ, et al. Calpain cleavage of the plasma membrane Na+/Ca2+ exchanger in excitotoxicity. Cell 2005; 120:275–285

    Article  CAS  PubMed  Google Scholar 

  15. Stout AK, Raphael HM, Kanterewicz BI, Klann E, Reynolds IJ. Glutamate-induced neuron death requires mitochondrial calcium uptake. Nat Neurosci 1998; 1:366–373

    Article  CAS  PubMed  Google Scholar 

  16. Soriano FX, Papadia S, Hofmann F, Hardingham NR, Bading H, Hardingham GE. Preconditioning doses of NMDA promote neuroprotection by enhancing neuronal excitability. J Neurosci 2006; 26:4509–4518

    Article  CAS  PubMed  Google Scholar 

  17. Iseda T, Nishio T, Kawaguchi S, et al. Spontaneous regeneration of the corticospinal tract after transection in young rats: a key role of reactive astrocytes in making favourable and unfavourable conditions for regeneration. Neuroscience 2004; 126:365–374

    Article  CAS  PubMed  Google Scholar 

  18. Kotter MR, Setzu A, Sim FJ, et al. Macrophage depletion impairs oligodendrocyte remyelination following lysolecithin-induced demyelination. Glia 2001; 35:204–212

    Article  CAS  PubMed  Google Scholar 

  19. Masson JL, Jones JJ, Taniike M, Morelll P, Suzuki K, Matsushima GK. Mature oligodendrocytes apoptosis precedes IGF-I production: an oligodendrocyte progenitor accumulation and differentiation during demyelination/remyelination. J Neurosci Res 2000; 61:251–262

    Article  Google Scholar 

  20. Arnett HA, Wang Y, Matsushima GK, Suzuki K, Ting JPY. Functional genomic analysis of remyelination reveals importance of infl ammation in oligodendrocytes regeneration. J Neurosci 2003; 23:9824–9832

    CAS  PubMed  Google Scholar 

  21. Marchetti L, Klein M, Schlett K, Pfizenmaier K, Eisel ULM. Tumor necrosis factor (TNF)-mediated neuroprotection against glutamate-induced excitotoxicity is enhanced by N-methyl-d-aspartate receptor activation. J Biol Chem 2004; 279(31):32869–32881

    Article  CAS  PubMed  Google Scholar 

  22. Becher B, Antel JP. Comparison of phenotypic and functional properties of immediately ex vivo and cultured human adult microglia. Glia 1996; 18:1–10

    Article  CAS  PubMed  Google Scholar 

  23. Windhangen A, Newcombe J, Dan-gond F, Strand C, Woodroofe MNB, Cuzner ML et al. Expression of costimulatory molecules B7–1 (CD80), B7–2 (CD86), and interleukin 12 cytokine in multiple sclerosis lesions. J Exp Med 1995; 182:1985–1996

    Article  Google Scholar 

  24. Pachter JS, de Vries HE, Fabry Z. The blood–brain barrier and its role in immune privilege in the central nervous system. J Neuropathol Exp Neurol 2003; 62:593–604

    CAS  PubMed  Google Scholar 

  25. Labiche LA, Grotta JC. Clinical trials for cytoprotection in Stroke. NeuroRx 2004; 1:46–70

    Article  PubMed  Google Scholar 

  26. Barnes MP, Dobkin BH, Bogousslavsky J. Recovery after Stroke. New York: Cambridge University Press, 2003

    Google Scholar 

  27. Read SJ, Parsons AA, Harrison DC, Philpott K, Kabnick K, O’Brien S. Stroke genomics: approaches to identify, validate, and understand ischemic stroke gene expression. J Cereb Blood Flow Metab 2001; 21:755–778

    Article  CAS  PubMed  Google Scholar 

  28. Danton GH, Dietrich WD. Inflammatory mechanisms after ischemia and stroke. J Neuropath Exp Neurol 2003; 62:127–136

    CAS  PubMed  Google Scholar 

  29. Ginsberg MD. Injury mechanisms in the ischemic penumbra. Approaches to neuroprotection in acute ischemic stroke. Cerebrovasc Dis 1997; 7(Suppl 2):7–12

    Article  Google Scholar 

  30. Millán M, Arenillas J. Gene expression in cerebral ischemia: a new approach for neuroprotection. Cerebrovasc Dis 2006; 21(Suppl 2):30–37

    PubMed  Google Scholar 

  31. Xerri C, Merzenich MM, Peterson BE, Jenkins W. Plasticity of primary somatosensory cortex paralleling sensorimotor skill recovery from stroke in adult monkeys. J Neurophysiol 1998; 79:2119–2148

    CAS  PubMed  Google Scholar 

  32. Kolb B, Gibb R, Gonzalez CL. Cortical injury and neuroplasticity during development. In Shaw C, McEachern JC (eds) Toward a Theory of Neuroplasticity. Philadelphia, Taylor & Francis; 2001, pp. 2223–2243

    Google Scholar 

  33. Beaulieu CL: Rehabilitation and outcome following pediatric traumatic brain injury. Surg Clin North Am 2002; 82:393–408

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, CFR University Hospital; University of Medicine and Pharmacy “Iuliu Hatieganu”, Cluj-Napoca, Romania

    Dafin F. Muresanu

Authors
  1. Dafin F. Muresanu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dafin F. Muresanu .

Editor information

Editors and Affiliations

  1. Sha'ar Menashe Mental Health Center, Hadera, 38814, Israel

    Michael S. Ritsner

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Muresanu, D.F. (2010). Towards a New Paradigm in Neuroprotection and Neuroplasticity. In: Ritsner, M. (eds) Brain Protection in Schizophrenia, Mood and Cognitive Disorders. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-8553-5_2

Download citation

Publish with us

Policies and ethics

Search

Navigation