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B-Cells in Stroke and Preconditioning-Induced Protection Against Stroke

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Non-Neuronal Mechanisms of Brain Damage and Repair After Stroke

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

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Abstract

It is well-understood that inflammation following stroke onset contributes to neuronal injury, blood–brain barrier (BBB) disruption, and functional deficits during recovery. But which leukocyte subsets critically contribute to injury, and more importantly which may be necessary for neurorepair, remains to be fully elucidated. One emerging concept is that B-cells, and specifically regulatory B-cells, exhibit the potential to contribute to anti-inflammatory, protective mechanisms during acute recovery. Unfortunately, few studies have investigated the role of B-cells during ischemic brain injury. This chapter reviews B-cell development and function, as well as the contribution of B-cells to pathology during other autoimmune diseases. This is followed by an overview of inflammatory mechanisms after stroke, with emphasis on a potential role for B-cells in post-stroke autoimmunity. Research will be summarized that highlights the role for B-cells in acute CNS neuroprotection after stroke, as well as new data suggesting that B-cells may be detrimental to long-term cognitive function in experimental stroke. Finally, this chapter will focus on preconditioning, a method by which non-injurious, noxious stimuli create an ischemia-tolerant phenotype to protect from stroke. Several preconditioning paradigms that affect B-cell function, including hypoxia, exercise, and exposure to lipopolysaccharide (LPS), will be reviewed, with an emphasis on the clinical relevance to populations at-risk for stroke. While more research is needed to clearly define the role of B-cells in post-stroke recovery, this chapter will highlight several mechanisms by which B-cells can directly influence recovery in the injured CNS.

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Abbreviations

APCs:

Antigen-presenting cells

BAFF:

B-cell-activating factor

BBB:

Blood–brain barrier

B cells:

B-lymphocytes

BCR:

B-cell receptor

BDNF:

Brain-derived neurotrophic factor

Bregs:

Regulatory B-cells

CCL2:

Chemokine (C–C motif) ligand 2

CLN:

Cervical lymph node

CNS:

Central nervous system

CSF:

Cerebrospinal fluid

CSPGs:

Chondroitin sulfate proteoglycans

CXCL13:

Chemokine (C–X–C motif) ligand 13

DAMPs:

Danger-associated molecular pattern molecules

EAE:

Experimental autoimmune encephalomyelitis

ICAM-1:

Intracellular adhesion molecule

Ig:

Immunoglobulin

IL-:

Interleukin

IFNγ:

Interferon γ

LPS:

Lipopolysaccharide

LTP:

Long-term potentiation

MAP2:

Microtubule-associated protein 2

MBP:

Myelin basic protein

MCAo:

Middle cerebral artery occlusion

MHC:

Major histocompatibility class

MOG:

Myelin oligodendrocyte glycoprotein

MS:

Multiple sclerosis

μMT−/− :

Transmembrane exon of the IgM heavy chain

MZ B-cells:

Marginal zone B-cells

NA:

Noradrenaline

nIgM:

Natural IgM

NR2A:

N-methyl-D-aspartate (NMDA) receptor subunit 2A

RA:

Rheumatoid Arthritis

RF:

Rheumatoid factor

RHP:

Repetitive hypoxic preconditioning

ROS:

Reactive oxygen species

Sema3a:

Semaphorin IIIa

SHP:

Single-exposure hypoxic preconditioning

SLE:

Systemic lupus erythematosus

TACI:

Transmembrane activator and calcium modulator and cyclophilin ligand interactor

TGF-β:

Transforming growth factor β

Th cells:

T helper cells

TLR:

Toll-like receptor

TNFα:

Tumor necrosis factor α

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  1. Department of Neurology & Neurotherapeutics, UT Southwestern Medical Center, 6000 Harry Hines Blvd, MC8813, Dallas, TX, 75390, USA

    Uma Maheswari Selvaraj, Katie Poinsatte & Ann M. Stowe

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  1. Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    Jun Chen

  2. Pittsburgh Institute of Brain Disorders and Recovery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    John H. Zhang

  3. Department of Anesthesiology, Loma Linda University School of Medicine, Loma Linda, California, USA

    Xiaoming Hu

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Selvaraj, U.M., Poinsatte, K., Stowe, A.M. (2016). B-Cells in Stroke and Preconditioning-Induced Protection Against Stroke. In: Chen, J., Zhang, J., Hu, X. (eds) Non-Neuronal Mechanisms of Brain Damage and Repair After Stroke. Springer Series in Translational Stroke Research. Springer, Cham. https://doi.org/10.1007/978-3-319-32337-4_12

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