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Handbook of Neurochemistry and Molecular Neurobiology pp 33–45Cite as

iNOS and COX‐2 in Ischemic Stroke

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Abstract:

Stroke remains a leading cause for mortality and morbidity in the world despite the intense effort in research and development for remedies. Although the detailed mechanisms leading to brain tissue damage after ischemic stroke are not totally known, it is clear that inflammation plays a key role in the development of such damage. Research over the years indicates that the major players in the postischemic inflammation are inducible nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX‐2). iNOS is expressed de novo after ischemic stroke and participates in the late phase of tissue damage. Inhibition of iNOS activity or iNOS gene deletion in rodent models of ischemic stroke provides neuroprotection. COX‐2 is induced in response to ischemic and neuroexcitotoxic injuries. COX‐2 inhibition with specific inhibitors reduces brain injury caused by focal ischemia. COX‐2 gene deletion provides similar protection. Although iNOS and COX‐2 are deleterious after stroke, recent evidence indicates that these enzymes can also be beneficial. Therefore, therapeutic approaches based on iNOS and COX‐2 inhibition have to target the neurotoxic effects, while sparing the beneficial effects of the enzymes.

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Abbreviations

CBF:

cerebral blood flow

C/EBP:

CCAAT/Enhancer Binding Protein

COX‐1:

cyclooxygenase‐1

COX‐2:

cyclooxygenase‐2

COX‐3:

cyclooxygenase‐3

HMG CoA:

(3‐hydroxy‐3‐methylglutary1)‐coenzyme A

JNK:

c‐jun N‐terminal kinase

IPC:

ischemic preconditioning

LPS:

lipopolysaccharide

MAPK:

mitogen activated protein kinase

MCA:

middle cerebral artery

NF‐IL6:

nuclear factor interleukin‐6

NMDA:

N‐methyl‐D‐aspartic acid

NO:

nitric oxide

NOS:

nitric oxide synthase

iNOS:

inducible NOS

nNOS:

neuronal NOS

eNOS:

endothelial NOS

PARP:

poly(ADP‐ribose) polymerase

PGH2:

prostaglandin H2

PGG2:

prostaglandin G2

PGE2:

prostaglandin E2

PGI2:

prostaglandin I2

PGD2:

prostaglandin D2

PGF2α:

prostaglandin F2α

RNA:

ribonucleic acid

ROS:

reactive oxygen species

SOD:

superoxide dismutase

tPA:

tissue plasminogen activator

UTR:

untranslated region

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Authors
  1. P. Zhou
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  2. C. Iadecola
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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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Zhou, P., Iadecola, C. (2007). iNOS and COX‐2 in Ischemic Stroke. 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_3

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