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

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


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.


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



Effect of Natalizumab on Infarct Volume in Acute Ischemic Stroke


Amyotrophic lateral sclerosis


Adenosine triphosphate


Arbitrary units


Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke


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


Food and Drug Administration


Field Randomization of NA-1 Therapy in Early Responders


Hydrogen peroxide


Hydroxyl radical





M1 or M2



Multipotent adult progenitor cells in acute ischemic stroke


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


Modified Rankin scale


Neodymium-doped yttrium aluminum garnet


Nicotinamide adenine dinucleotide phosphate


Nicotinamide adenosine dinucleotide


NeuroThera® Efficacy and Safety Trial


National Institutes of Health


National Institutes of Health Stroke Scale


National Institute of Neurological Disorders and Stroke




Neuronal Nitric oxide synthase


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


Superoxide anion radical


Human neural stem cells in patients with chronic ischaemic stroke


PSD-95 (postsynaptic density protein 95


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


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


Solitaire With the Intention For Thrombectomy as PRIMary Endovascular Treatment

TCA cycle

Tricarboxylic acid cycle


TP53-inducible regulator of glycolysis and apoptosis


Transcranial laser therapy


Tissue plasminogen activator


THRombectomie des Arteres CErebrales


Triphenyl tetrazolium chloride




Very late antigen-4


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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