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Modulation of Post-Stroke Plasticity and Regeneration by Stem Cell Therapy and Exogenic Factors

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Cellular and Molecular Approaches to Regeneration and Repair

Part of the book series: Springer Series in Translational Stroke Research ((SSTSR))

Abstract

Revascularization therapy in the acute post-stroke phase nowadays is reducing the grade of disability and mortality after cerebral ischemia. Post-acute to chronic therapeutic strategies in the phase of irreversible brain parenchyma damage showed until now controversial results in pre-clinical studies: currently there are no effective treatment strategies apart from neurological rehabilitation aiming at restoration of functional post-ischemic deficits.

Spontaneous functional recovery appears immediately after stroke and was proven to correlate with the endogenous regeneration potential represented by rewiring of neuronal circuits through promotion of dendritic and axonal sprouting, improving axonal function, synaptogenesis, neurogenesis, and angiogenesis. These observations have led to numerous preclinical studies investigating a new therapeutic direction after stroke, the neurovascular restoration impacting stroke recovery potential.

This chapter summarizes achievements to date, current challenges and ongoing research in the field of regenerative processes after ischemic stroke, focusing on the formation of functional anatomical pathways responsible for enhanced recovery.

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Abbreviations

AMPA:

Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

AQP:

Aquaporin

ATSC:

Adipose-tissue stem cell

BBB:

Blood-brain barrier

BDNF:

Brain-derived neurotrophic factor

BMSC:

Bone-marrow derived stem cell

BrdU:

5-Bromo-2′-deoxyuridine

CCL2:

C-C chemokine ligand 2

CCR2:

C-C chemokine receptor type 2

CM:

Conditioned medium

CNS:

Central nervous system

DCX:

Doublecortin

EC:

Endothelial cell

EPC:

Endothelial progenitor cell

Epo:

Erythropoietin

ERK:

Extracellular signal-regulated kinase

ESC:

Embryonic stem cell

GABA:

Gamma aminobutyric acid

GFAP:

Glial fibrillary acidic protein

HIF-1:

Hypoxia-inducible factor-1

HuNu:

Human nuclear antigen

IL:

Interleukin

LTD:

Long term depression

LTP:

Long term potentiation

LV:

Lateral ventricle

MAPK:

Mitogen activated protein kinase

MMP:

Matrix metalloproteinase

NMDA:

N-methyl-D-aspartate

NPC:

Neural progenitor cell

NO:

Nitric oxide

NSC:

Neural stem cell

PI3K:

Phosphoinositide 3-kinase

Robo:

Roundabout protein

SEM:

Standard error of the mean

SGZ:

Subgranular zone

STDP:

Spike timing depending plasticity

SVZ:

Subventricular zone

TPEN:

N,N,N′,N′-tetrakis-(2-pyridylmethyl)ethylenediamine

TSP:

Thrombospondin

TuJ1:

Neuron-specific class III beta-tubulin

UCBC:

Umbilical cord blood stem cell

VCAM-1:

Vascular cell adhesion molecule 1

VEGF:

Vascular endothelial growth factor

VLA-4:

Very large antigen-4

Zn:

Zinc

Zn2+ :

Ionic zinc

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Acknowledgements

This research was funded by the Swiss National Science Foundation (Grants No. 31-064975.01, 31-050824, 31-102075/1, 3100A0-112529, 31003A-135565, 406340-128124, 146632, PBBEB-117034, PASMP3-123221/1, PBBEB-146099 and PBBEB-155299), the Swiss Parkinson Foundation, the HANELA Foundation, a Research Grant from the University Hospital Berne, Inselspital (RGI-84800855), the Evelyn L. Neizer Fund, and by the Department of Clinical Research at the University of Berne.

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Authors and Affiliations

  1. Department of Neurosurgery, University of Berne, Inselspital, Berne, Switzerland

    Lukas Andereggen, Raluca Reitmeir, Stefano Di Santo, Hans R. Widmer, Serge Marbacher & Robert H. Andres M.D.

  2. Department of Neurosurgery and F.M. Kirby Neurobiology Center, Harvard Medical School, Boston, MA, USA

    Lukas Andereggen

  3. Department of Neurosurgery, University Hospital Basel, Basel, Switzerland

    Raphael Guzman

  4. Department of Neurosurgery and Stanford Stroke Center, Stanford University School of Medicine, Stanford, CA, USA

    Raphael Guzman & Robert H. Andres M.D.

  5. Department of Neurosurgery, Cantonal Hospital of Aarau, Aarau, Switzerland

    Serge Marbacher

  6. Department of Clinical Research, University of Berne, Berne, Switzerland

    Robert H. Andres M.D.

  7. Department of Neurosurgery, Research Laboratory, Inselspital, Pavillon 47, Freiburgstrasse 10, 3010, Berne, Switzerland

    Robert H. Andres M.D.

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  1. Lukas Andereggen
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  5. Hans R. Widmer
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  7. Robert H. Andres M.D.
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Correspondence to Robert H. Andres M.D. .

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  1. Department of Neurology & Neurosurgery, Cedars-Sinai Medical Center, AHSP, Los Angeles, California, USA

    Paul A. Lapchak

  2. Department of Physiology, Loma Linda University, Loma Linda, California, USA

    John H. Zhang

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Andereggen, L. et al. (2018). Modulation of Post-Stroke Plasticity and Regeneration by Stem Cell Therapy and Exogenic Factors. In: Lapchak, P., Zhang, J. (eds) Cellular and Molecular Approaches to Regeneration and Repair. Springer Series in Translational Stroke Research. Springer, Cham. https://doi.org/10.1007/978-3-319-66679-2_7

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  • DOI: https://doi.org/10.1007/978-3-319-66679-2_7

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