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Integrating Molecular, Cellular, and Systems Approaches to Repairing the Brain After Stroke

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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

A stroke implies a sudden and spontaneous onset of neurological symptoms due to a vascular insult. Despite the brain’s inherent capacity for plasticity and spontaneous improvement, strokes still leave many patients with devastating deficits that can permanently affect independence and quality of life. This chapter focuses on ways to help restore the functionality of the central nervous system (CNS) after this type of injury. Understanding how neurons interact on both individual (i.e. cellular and molecular) and population (i.e. synapses and circuits) levels is crucial to developing successful restorative strategies, as is appreciating how these interactions change over the injury-recovery timeline. The CNS has several characteristics that make its restitution exceptionally difficult; beyond even its incredible intricacy, its parenchymal cells, or neurons, do not regenerate well after injury, and this damaged neuronal substrate embodies a consciousness system that must be engaged in its own recovery. In fact, there is now data suggesting that conscious intention, often invoked through goal-oriented rehabilitation, plays a crucial role in facilitating functional plasticity and long-range axonal sprouting. To capitalize on this principle, neural interfaces and electrical stimulation strategies are being integrated into rehabilitation paradigms to provide critically-timed feedback that can reinvigorate injured circuits. Combining these approaches with interventions at the cellular and molecular level (e.g. immunological or genetic modulations aimed at promoting neuronal outgrowth, or stem cells that can replace damaged parenchyma) has the chance to improve neurological recovery to back toward baseline levels. Ultimately, because cells of the CNS do not regrow on their own, and because regrowth and synapse formation does not necessarily ensure restoration of function, harmonious application of synergistic approaches at both the micro- and macroscopic levels will be needed to establish long-lasting functional plasticity and meaningful recovery.

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Abbreviations

AMPA:

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

AP:

Action potential

BCI:

Brain-computer interface

BCM:

Bienenstock–Cooper–Munro

BMI:

Brain-machine interface

BSDS:

Brain state dependent stimulation

cAMP:

Cyclic adenosine monophosphate

CIMT:

Constraint-induced movement therapy

CNS:

Central nervous system

CNTF:

Ciliary neurotrophic factor

CPP:

Cerebral perfusion pressure

CSPG:

Chondroitin sulfate proteoglycans

DBS:

Deep brain stimulation

DOC:

Disorder of consciousness

DRG:

Dorsal root ganglion

FDA:

Federal Drug Administration

FES:

Functional electrical stimulation

GABA:

Gamma-aminobutyric acid

GAP43:

Growth associated protein 43

GDF10:

Growth and differentiation factor 10

ICA:

Internal carotid artery

ICP:

Intracranial pressure

IFG-1:

Insulin-like growth factor 1

LTD:

Long-term depression

LTP:

Long-term potentiation

M1:

Primary motor cortex

MAG:

Myelin-associated

MAI:

Myelin-associated inhibitory molecule

MCA:

Middle cerebral artery

mTOR:

Mechanistic target of rapamycin

NgR:

Nogo receptor

NMDA:

N-Methyl-d-aspartate

NSAID:

Non-steroidal anti-inflammatory drug

OMgp:

Oligodendrocyte-myelin glycoprotein

OPN:

Osteopontin

PAS:

Paired associative stimulation

PMC:

Premotor cortices

PTEN:

Phosphatase and tensin homolog

RGC:

Retinal ganglion cell

rTMS:

Repetitive transcranial magnetic stimulation

SCI:

Spinal cord injury

SGZ:

Subgranular zone

STDP:

Spike-timing dependent plasticity

SVZ:

Subventricular zone

TGF-β:

Transforming growth factor beta

TGFβR:

Transforming growth factor beta receptor

TMS:

Transcranial magnetic stimulation

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The authors declare they have no conflict of interest.

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Authors and Affiliations

  1. Department of Neurosurgery, Duke University Medical Center, Duke Neurosurgery Box 3807, Durham, NC, 27710, USA

    Max O. Krucoff M.D., Stephen C. Harward M.D., Ph.D., Shervin Rahimpour M.D., Erik F. Hauck M.D., Shivanand P. Lad M.D., Ph.D. & Dennis A. Turner M.D., M.A

  2. Department of Neurology, Duke University Medical Center, Durham, NC, 27710, USA

    Keith Dombrowski M.D.

  3. Department of Neurobiology, Duke University, Durham, NC, 27710, USA

    Dennis A. Turner M.D., M.A

  4. Research and Surgery Services, Durham Veterans Affairs Medical Center, Durham, NC, USA

    Dennis A. Turner M.D., M.A

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  1. Max O. Krucoff M.D.
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Correspondence to Max O. Krucoff 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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Krucoff, M.O. et al. (2018). Integrating Molecular, Cellular, and Systems Approaches to Repairing the Brain After Stroke. 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_18

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