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Immunology of Ischemic Stroke: Impact, Mechanisms, and Immunomodulatory Therapies

  • Chapter
  • First Online:
Translational Research in Stroke

Part of the book series: Translational Medicine Research ((TRAMERE))

  • 1144 Accesses

Abstract

It is increasingly recognized that ischemic stroke is not only a brain disease characterized by brain cell death and damage but is also marked by the dysfunction of immune organs, as evidenced by systematic immune dysregulation prior to or after cerebral ischemia. For instance, with the prevalence of comorbidities such as diabetes, obesity, and hypertension, pre-existing chronic systematic inflammation has been considered an essential contributor that exacerbates stroke pathology. Conversely, mild immune responses induced by preconditioning have also been shown to protect against cerebral ischemic injury. Moreover, once stroke occurs, the injured brain evokes immune responses both in the brain and in the peripheral by communicating with the immune system via danger-associated molecular patterns or antigens, cytokines, and chemokines as well as via specific neural circuits, such as the sympathetic and parasympathetic nervous system. This bidirectional communication between the injured brain and the immune system determines the progression of acute infarct damage, long-term tissue repair, as well as postischemic systematic immunosuppression. In summary, the pre-existing immune responses as well as the immune responses evoked by cerebral ischemia play essential roles in shaping stroke outcomes. The therapies that target the immune responses, especially the immunomodulatory therapies, are promising treatments for ischemic stroke.

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Abbreviations

ANS:

Autonomic nervous system

APC:

Antigen processed cells

ApoE:

Apolipoprotein E

BBB:

Blood–brain barrier

CARDs:

Caspase activation and recruitment domains

CCL2:

Monocyte chemotactic protein-1

CCL3:

Macrophage inflammatory protein-α

CCL5:

Chemokine (C-C motif) ligand 5

CCR:

C-C chemokine receptor

CD:

Cluster of differentiation

CRH:

Corticotrophin-releasing hormone

CX3CR1:

C-X3-C motif chemokine receptor

DCs:

Dendritic cells

HDAC:

Histone deacetylase

HIFs:

Hypoxia inducible factors

HMGB1:

High-mobility group box-1

HPA:

Hypothalamic–pituitary–adrenal

ICAM:

Intercellular adhesion molecule

IL:

Interleukin

iNKTs:

Invariant natural killer T cells

LFA-1:

Lymphocyte function-associated antigen-1

LPS:

Lipopolysaccharide

MAP 2:

microtubule-associated protein 2

MBP:

Myelin basic protein

MCP-1:

Monocyte chemoattractant protein-1

MMP:

Metalloproteinase

MOG:

Myelin oligodendrocyte glycoprotein

nACH:

Nicotinic acetylcholine receptors

NLRs:

NOD-like receptors

NLRP1:

NLR family pyrin domain containing 1

NPCs:

Neural progenitor cells

OGD:

Oxygen-glucose deprivation

OPCs:

Oligodendrocyte precursor cells

PET:

Positron emission tomography

PNSN:

Parasympathetic nervous system

PVN:

Paraventricular nucleus

Rag1:

Recombination-activating gene 1

RAGE:

Receptor for advanced glycation end products

RANTES:

Regulated on activation, normal T cell expressed and secreted

S1P:

Sphingosine-1-phosphate

SCID:

Severe combined immunodeficiency mice

SDF1:

Stromal cell-derived factor 1

siRNA:

Small interfering RNA

SNS:

Sympathetic nervous system

Th:

T helper

TLR:

Toll-like receptor

tPA:

Tissue plasminogen activator

Tregs:

Regulatory T cells

VCAM:

Vascular adhesion molecule

vMIP-II:

Virus-derived macrophage inflammatory protein-II

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Acknowledgments

This work was financially supported by grants from the National Science Foundation of China (81371278, 81471336, 81373382). Additionally, the program was supported by grants from the Priority Academic Program Development of the Jiangsu Higher Education Institutes (PAPD) and Suzhou Clinical Research Center of Neurological Disease (Szzx201503).

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Authors and Affiliations

  1. Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psychiatric-Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, 215021, China

    Jia Jia

  2. Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and Institute of Neuroscience, Soochow University, 199 Renai Road, Suzhou, Jiangsu Province, 215123, China

    Jian Cheng

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  1. Jia Jia
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  2. Jian Cheng
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Correspondence to Jian Cheng .

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Editors and Affiliations

  1. Department of Neurology & Neurosurgery, Cedars-Sinai Medical Center, Advanced Health Sciences Pavilion, Los Angeles, California, USA

    Paul A. Lapchak

  2. Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China

    Guo-Yuan Yang

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Jia, J., Cheng, J. (2017). Immunology of Ischemic Stroke: Impact, Mechanisms, and Immunomodulatory Therapies. In: Lapchak, P., Yang, GY. (eds) Translational Research in Stroke. Translational Medicine Research. Springer, Singapore. https://doi.org/10.1007/978-981-10-5804-2_12

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