Biomaterial Database

NADPH-diaphorase activity in activated astrocytes represents inducible nitric oxide synthase. 1994

M N Wallace, and S K Bisland

Department of Biomedical Sciences, Marischal College, University of Aberdeen, U.K.

In paraformaldehyde-fixed sections of healthy brain, glial cells at the light-microscope level do not contain measurable levels of NADPH-diaphorase. However, after a variety of lesions in the mouse brain, some reactive astrocytes express varying amounts of this enzyme. Following stab wounds, activated astrocytes or related glial cells surrounding the lesion, contained moderate to high levels of NADPH-diaphorase in the cerebellum, midbrain, thalamus, striatum, hippocampal formation and neocortex. Double-labelling experiments confirmed that this corresponds to an inducible form of nitric oxide synthase, similar to that found in activated macrophages. Within the lesion there were large numbers of macrophages which also contained NADPH-diaphorase. After 10 min of global hypoxic ischaemia, some reactive astrocytes also contained NADPH-diaphorase. These cells were confined to the dorsal part of the hippocampal formation (the dentate fascia and CA1 areas) and to the anterolateral striatum. More focal ischaemic damage, produced by dividing an arterial branch, also produced a rim of reactive astrocytes containing NADPH-diaphorase, that surrounded the area of necrosis. Low levels of NADPH-diaphorase were induced within one day of a stab wound and the enzyme activity reached near maximal levels by two days postlesion. Moderate NADPH-diaphorase activity was still present at 63 days postlesion, but only a small number of astrocytes were stained in the immediate vicinity of the lesion. These experiments confirm that NADPH-diaphorase activity represents inducible nitric oxide synthase in activated astrocytes and probably in inflammatory macrophages. We conclude that a high proportion of activated astrocytes and a small proportion of invading macrophages are induced to express moderate to high levels of nitric oxide synthase following neuronal damage. Our results indicate that following a variety of lesions reactive astrocytes are synthesizing significant levels of nitric oxide within 24 h. This nitric oxide may be involved in modulating the likelihood of epileptic seizures.

UI	MeSH Term	Description	Entries
D008264	Macrophages	The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)	Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D008297	Male		Males
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009252	NADPH Dehydrogenase	A flavoprotein that reversibly oxidizes NADPH to NADP and a reduced acceptor. EC 1.6.99.1.	NADP Dehydrogenase,NADP Diaphorase,NADPH Diaphorase,Old Yellow Enzyme,TPN Diaphorase,Dehydrogenase, NADP,Dehydrogenase, NADPH,Diaphorase, NADP,Diaphorase, NADPH,Diaphorase, TPN,Enzyme, Old Yellow
D009419	Nerve Tissue Proteins		Proteins, Nerve Tissue,Tissue Proteins, Nerve
D001930	Brain Injuries	Acute and chronic (see also BRAIN INJURIES, CHRONIC) injuries to the brain, including the cerebral hemispheres, CEREBELLUM, and BRAIN STEM. Clinical manifestations depend on the nature of injury. Diffuse trauma to the brain is frequently associated with DIFFUSE AXONAL INJURY or COMA, POST-TRAUMATIC. Localized injuries may be associated with NEUROBEHAVIORAL MANIFESTATIONS; HEMIPARESIS, or other focal neurologic deficits.	Brain Lacerations,Acute Brain Injuries,Brain Injuries, Acute,Brain Injuries, Focal,Focal Brain Injuries,Injuries, Acute Brain,Injuries, Brain,Acute Brain Injury,Brain Injury,Brain Injury, Acute,Brain Injury, Focal,Brain Laceration,Focal Brain Injury,Injuries, Focal Brain,Injury, Acute Brain,Injury, Brain,Injury, Focal Brain,Laceration, Brain,Lacerations, Brain
D002534	Hypoxia, Brain	A reduction in brain oxygen supply due to ANOXEMIA (a reduced amount of oxygen being carried in the blood by HEMOGLOBIN), or to a restriction of the blood supply to the brain, or both. Severe hypoxia is referred to as anoxia and is a relatively common cause of injury to the central nervous system. Prolonged brain anoxia may lead to BRAIN DEATH or a PERSISTENT VEGETATIVE STATE. Histologically, this condition is characterized by neuronal loss which is most prominent in the HIPPOCAMPUS; GLOBUS PALLIDUS; CEREBELLUM; and inferior olives.	Anoxia, Brain,Anoxic Encephalopathy,Brain Hypoxia,Cerebral Anoxia,Encephalopathy, Hypoxic,Hypoxic Encephalopathy,Anoxia, Cerebral,Anoxic Brain Damage,Brain Anoxia,Cerebral Hypoxia,Hypoxia, Cerebral,Hypoxic Brain Damage,Anoxic Encephalopathies,Brain Damage, Anoxic,Brain Damage, Hypoxic,Damage, Anoxic Brain,Damage, Hypoxic Brain,Encephalopathies, Anoxic,Encephalopathies, Hypoxic,Encephalopathy, Anoxic,Hypoxic Encephalopathies
D002540	Cerebral Cortex	The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulci. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions.	Allocortex,Archipallium,Cortex Cerebri,Cortical Plate,Paleocortex,Periallocortex,Allocortices,Archipalliums,Cerebral Cortices,Cortex Cerebrus,Cortex, Cerebral,Cortical Plates,Paleocortices,Periallocortices,Plate, Cortical
D002545	Brain Ischemia	Localized reduction of blood flow to brain tissue due to arterial obstruction or systemic hypoperfusion. This frequently occurs in conjunction with brain hypoxia (HYPOXIA, BRAIN). Prolonged ischemia is associated with BRAIN INFARCTION.	Cerebral Ischemia,Ischemic Encephalopathy,Encephalopathy, Ischemic,Ischemia, Cerebral,Brain Ischemias,Cerebral Ischemias,Ischemia, Brain,Ischemias, Cerebral,Ischemic Encephalopathies
D004790	Enzyme Induction	An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.	Induction, Enzyme