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Stroke: Cytoprotection, Repair and Regeneration—The Continuum of Patient Care

  • Paul A. Lapchak
Chapter
Part of the Springer Series in Translational Stroke Research book series (SSTSR)

Abstract

The ischemic penumbra is now defined as tissue at risk of becoming fully involved in the evolving neurodegenerative process following an embolic stroke. After an ischemic core is quickly developed following vascular occlusion, there is slow spreading of the ischemic injury from the core to areas immediately surrounding the core until full recruitment is achieved. Forty years ago, seminal electrophysiological studies forming the basis of the penumbral hypothesis were conducted in a large animal model, baboons, an animal that is now rarely used in translational stroke research because it can no longer be justified! Thereafter, the rabbit embolic stroke model led the way for approval of Alteplase® (tissue plasminogen activator, tPA, rt-PA) to treat acute ischemic stroke.

Stroke research continues to evolve with the use of rodents primarily mice, rats, Oryctolagus cuniculus (rabbits), and occasionally non-human primates, but recent scientific expert statements have now suggested that non-human primates are not essential for stroke therapy development. One commonality amongst all species used historically is the documented presence of a core and penumbra following vascular occlusion, whether it be an artificial suture or clip occlusion or a blood clot.

This article reviews the historical basis for a few select mechanisms that are currently being targeted for cytoprotection, the rationale for target engagement to arrest penumbral growth and reduce clinical deficits, and it also sets a basis for the future of regeneration strategies to treat stroke patients.

Keywords

Translational Neuroprotection Neuroprotective Cytoprotection Brain Stroke Embolic Hemorrhage Clinical trial NIHSS Stem cell regeneration 

Abbreviations

ACTION

Effect of Natalizumab on Infarct Volume in Acute Ischemic Stroke

ALS

Amyotrophic lateral sclerosis

ATP

Adenosine triphosphate

AU

Arbitrary units

ESCAPE

Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke

EXTEND-IA

Trial and Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial

FDA

Food and Drug Administration

FRONTIER

Field Randomization of NA-1 Therapy in Early Responders

H2O2

Hydrogen peroxide

HO•

Hydroxyl radical

ICB

Intracerebral

IV

Intravenous

M1 or M2

Macrophage

MASTERS

Multipotent adult progenitor cells in acute ischemic stroke

MR CLEAN

Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands

mRS

Modified Rankin scale

Nd:YaG

Neodymium-doped yttrium aluminum garnet

NADPH

Nicotinamide adenine dinucleotide phosphate

NADH

Nicotinamide adenosine dinucleotide

NEST

NeuroThera® Efficacy and Safety Trial

NIH

National Institutes of Health

NIHSS

National Institutes of Health Stroke Scale

NINDS

National Institute of Neurological Disorders and Stroke

NMDA

N-methyl-D-aspartate

nNOS

Neuronal Nitric oxide synthase

OPB

2-Oxo-3-(phenylhydrazone)-butanoic acid

O2•−

Superoxide anion radical

PISCES

Human neural stem cells in patients with chronic ischaemic stroke

PSD-95

PSD-95 (postsynaptic density protein 95

PDZ1-2

Postsynaptic density-95, discs large 1, zonula occludens-1

REVASCAT

Endovascular Revascularization With Solitaire Device Versus Best Medical Therapy in Anterior Circulation Stroke Within 8 Hours

SWIFT PRIME

Solitaire With the Intention For Thrombectomy as PRIMary Endovascular Treatment

TCA cycle

Tricarboxylic acid cycle

TIGAR

TP53-inducible regulator of glycolysis and apoptosis

TLT

Transcranial laser therapy

tPA

Tissue plasminogen activator

THRACE

THRombectomie des Arteres CErebrales

TTC

Triphenyl tetrazolium chloride

UV

Ultraviolet

VLA-4

Very late antigen-4

Notes

Acknowledgments and Funding

This article was written without direct financial support from government sources (PAL). PAL is supported by pharmaceutical industry grants and philanthropic donations. P. Butte is thanked for assistance with NADH measurements.

Conflict of Interest Statements: PAL is Editor-in-Chief, Journal of Neurology & Neurophysiology and Associate Editor, Translational Stroke Research.

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Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Neurology & NeurosurgeryCedars-Sinai Medical Center, Advanced Health Sciences PavilionLos AngelesUSA

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