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

  • Lukas Andereggen
  • Raluca Reitmeir
  • Stefano Di Santo
  • Raphael Guzman
  • Hans R. Widmer
  • Serge Marbacher
  • Robert H. Andres
Chapter
Part of the Springer Series in Translational Stroke Research book series (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.

Keywords

Stroke Regeneration Plasticity Repair Stem cells Neural progenitors Neurogenesis Neuroprotection Endothelial progenitors Trophic factors 

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

Notes

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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Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Lukas Andereggen
    • 1
    • 2
  • Raluca Reitmeir
    • 1
  • Stefano Di Santo
    • 1
  • Raphael Guzman
    • 3
    • 4
  • Hans R. Widmer
    • 1
  • Serge Marbacher
    • 1
    • 5
  • Robert H. Andres
    • 1
    • 4
    • 6
    • 7
  1. 1.Department of NeurosurgeryUniversity of Berne, InselspitalBerneSwitzerland
  2. 2.Department of Neurosurgery and F.M. Kirby Neurobiology CenterHarvard Medical SchoolBostonUSA
  3. 3.Department of NeurosurgeryUniversity Hospital BaselBaselSwitzerland
  4. 4.Department of Neurosurgery and Stanford Stroke CenterStanford University School of MedicineStanfordUSA
  5. 5.Department of NeurosurgeryCantonal Hospital of AarauAarauSwitzerland
  6. 6.Department of Clinical ResearchUniversity of BerneBerneSwitzerland
  7. 7.Department of Neurosurgery, Research LaboratoryInselspitalBerneSwitzerland

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