Book contents
- Frontmatter
- Contents
- List of contributors
- Preface
- Acknowledgments
- Part I Special lectures
- Part II Oxidative stress
- 3 Peroxynitrite and injury to the vasculature and central nervous system in stroke and neurodegeneration
- 4 Interaction between inducible nitric oxide and cyclooxygenase-2 in ischemic brain injury
- 5 Mechanisms of ischemic tolerance
- 6 Clinically tolerated NMDA receptor antagonists and newly cloned NMDA receptor subunits that mimic them
- Part III Apoptosis
- Part IV Hot topics
- Part V Hemorrhage, edema and secondary injury
- Part VI Inflammation
- Part VII Gene transfer and therapy
- Part VIII Neurogenesis and plasticity
- Part IX Magnetic resonance imaging in clinical stroke
- Part X Risk factors, clinical trials and new therapeutic horizons
- Index
- Plate section
4 - Interaction between inducible nitric oxide and cyclooxygenase-2 in ischemic brain injury
from Part II - Oxidative stress
Published online by Cambridge University Press: 02 November 2009
- Frontmatter
- Contents
- List of contributors
- Preface
- Acknowledgments
- Part I Special lectures
- Part II Oxidative stress
- 3 Peroxynitrite and injury to the vasculature and central nervous system in stroke and neurodegeneration
- 4 Interaction between inducible nitric oxide and cyclooxygenase-2 in ischemic brain injury
- 5 Mechanisms of ischemic tolerance
- 6 Clinically tolerated NMDA receptor antagonists and newly cloned NMDA receptor subunits that mimic them
- Part III Apoptosis
- Part IV Hot topics
- Part V Hemorrhage, edema and secondary injury
- Part VI Inflammation
- Part VII Gene transfer and therapy
- Part VIII Neurogenesis and plasticity
- Part IX Magnetic resonance imaging in clinical stroke
- Part X Risk factors, clinical trials and new therapeutic horizons
- Index
- Plate section
Summary
Introduction
Cerebral ischemic injury is the end product of a multitude of pathogenic factors acting in a coordinated fashion. Thus ionic and chemical changes, initiated by ischemia-induced energy failure, lead to a wide variety of biochemical and genomic effects that ultimately result in tissue damage (Figure 4.1) (reviewed by ref. 2). These biochemical and molecular events are associated with marked cellular changes (reviewed by ref. 3). While neurons and glia develop swelling, circulating white cells adhere to cerebral endothelial cells and invade the brain parenchyma. Furthermore, astrocytes and microglia become activated, while macrophages accumulate in the injured areas. Invasion of the brain tissue by blood-borne white cells and the activation of microglia contribute to the development of brain damage. However, the mechanisms by which these inflammatory cells exert their deleterious effects are not well understood. Evidence accumulated over the past several years suggests that nitric oxide (NO) and cyclooxygenase (COX) products are involved in the mechanisms by which postischemic inflammation contributes to ischemic brain injury. In this chapter, this evidence will be reviewed and discussed in the context of the interactions between NO produced by inducible nitric oxide synthase (iNOS) and COX-2.
Neuromodulatory and neurotoxic actions of nitric oxide
NO is a molecular mediator that is synthesized by the enzyme NOS from l-arginine. Three isoforms of NOS have been described: neuronal NOS (nNOS), endothelial NOS (eNOS), and iNOS.
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- Information
- Cerebrovascular Disease22nd Princeton Conference, pp. 47 - 57Publisher: Cambridge University PressPrint publication year: 2002
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