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Cerebral Endothelial Cell Reaction to Ischemic Insults

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Abstract:

Clinical as well as basic research in the past decades has revealed the crucial importance of cerebral endothelial cell (CEC) dysfunction contributing to secondary injury following primary brain ischemic insults. Multiple postischemic events including inflammation, blood–brain barrier (BBB) breakdown, vasogenic brain edema, and hemorrhagic transformation are known to worsen the clinical outcomes of stroke patients, all of which are closely associated with CEC dysfunction. Oxidative stress with excessive production of reactive oxygen species (ROS) or free radicals has been considered to be one of the major factors in causing ischemic brain damages. In this chapter, we first discuss the sources of ROS and its contribution to vascular injury as well as recent progresses using antioxidant enzymes, most notably SOD and catalase, to attenuate ischemic injury. Cerebral ischemia results in damages of the brain vasculature with breaching of the normally impermeable BBB, thereby leading to vasogenic brain edema after stroke. We then review the potential importance of several proteins known to be involved in BBB breakdown after stroke, including matrix metalloproteinases (MMPs), endothelin, vascular endothelial growth factor (VEGF), angiopoietin, and nitric oxide synthase (NOS). Postischemic inflammatory reaction is another detrimental event causing secondary vascular injury, and thus exacerbating the primary ischemic damage. CEC dysfunction may promote adherence and infiltration of inflammatory cells, including neutrophils, macrophages, lymphocytes, and platelets. Therefore, cell and protein mediators contributing to postischemic inflammation are discussed. We also discuss several redox‐sensitive transcription factors including hypoxia‐inducible factor‐1 (HIF‐1), nuclear factor kappa‐B (NF‐κB), and activator protein‐1 (AP‐1) that are activated after cerebral ischemia to alter CEC viability and postischemic angiogenesis. Finally, potential therapeutic strategies such as statins, ischemic preconditioning (IPC) or LPS preconditioning, and prostaglandins that have been shown to exert protective effects in the settings of cerebral ischemia via mechanisms involving endothelial functions are emphasized.

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Abbreviations

AIF:

apoptosis‐inducing factor

AP‐1:

activator protein‐1

Ang‐1:

angiopoietin‐1

ATM:

ataxia telangectasia

BBB:

blood‐brain barrier

BDNF:

brain‐derived neutrophic factor

CEC:

cerebral endothelial cells

CNS:

central nervous system

COX‐1:

cycloxygenase‐1

CRP:

C‐reactive protein

Cu/Zn‐SOD:

copper/zinc superoxide dismutase

eNOS:

endothelial nitric oxide synthase

EPO:

erythropoietin

ERK:

extracellular signal‐regulated kinase

ET‐1:

endothelin‐1

FRA:

Fos‐related antigen

GC:

guanylate cyclase

GR:

glucocorticoid receptor

GSNO:

S‐nitrosoglutathione

HIF:

hypoxia‐inducible factor

HMG:

3‐hydroxy‐3‐methylglutaryl

HO‐1:

heme oxygenase‐1

HRE:

hypoxia‐response element

ICAM‐1:

intercellular adhesion molecule‐1

iNOS:

inducible nitric oxide synthase

IPC:

ischemic preconditioning

JNK:

c‐Jun N‐terminal kinase

L‐NA:

N(omega)‐nitro‐L‐arginine

L‐NAME:

N(G)‐nitro‐L‐arginine methyl ester

LPS:

lipopolysaccharide

MAPK:

mitogen‐activated protein kinase

MCAO:

middle cerebral artery occlusion

MMP:

matrix metalloproteinase

Mn‐SOD:

manganese superoxide dismutase

NAC:

N‐acetylcysteine

NAD:

nicotinamide adenine dinucleotide

NADPH:

reduced form of nicotinamide adenine dinucleotide phosphate

NF‐κB:

nuclear factor kappa‐B

nNOS:

neuronal nitric oxide synthase

NO:

nitric oxide

NOS:

nitric oxide synthase

OGD:

oxygen‐glucose deprivation

PARP‐1:

poly(ADP‐ribose) polymerase‐1

PGI2 :

prostacyclin

PGIS:

prostacyclin synthase

PI3K:

phosphatidylinositol 3‐kinase

PPAR‐γ:

peroxisome proliferators‐activated receptor‐gamma

rhVEGF:

recombinant human vascular endothelial growth factor

RNS:

reactive nitrogen species

ROS:

reactive oxygen species

SOD:

superoxide dismutase

Stat:

signal transducer and activator of transcription

tPA:

tissue plasminogen activator

TSP‐1:

thrombospondin‐1

TWEAK:

tumor necrosis factor‐like weak inducer of apoptosis

VCAM‐1:

vascular cell adhesion molecule‐1

VEGF:

vascular endothelial growth factor

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Authors
  1. D.‐I Yang
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  2. T.‐N. Lin
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  3. K.‐J. Yin
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  4. C.‐J. Hu
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  5. S.‐D. Chen
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  6. J. Xu
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  7. C. Y. Hsu
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Editor information

Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, 10962, Orangeburg, Newyork, USA

    Abel Lajtha (Director) (Director)

  2. Department of Neurosurgery, Department of Neurology and Neurological Sciences, and Program in Neurosciences, Stanford University School of Medicine, Stanford, California, 94305-5487, USA

    Pak H. Chan (Director Neurosurgical Labouratories) (Director Neurosurgical Labouratories)

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© 2007 Springer Science+Business Media, LLC

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Yang, D. et al. (2007). Cerebral Endothelial Cell Reaction to Ischemic Insults. In: Lajtha, A., Chan, P.H. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, New York, NY. https://doi.org/10.1007/978-0-387-30383-3_10

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