Chapter 18 Expression of nitric oxide synthase-2 in glia associated with CNS pathology

This chapter discusses the expression of nitric oxide synthase-2 (NOS-2) in glia associated with central nervous system (CNS) pathology. The production of nitric oxide (NO) in the nervous system is catalyzed by three, highly homologous isoforms of NO synthase (NOS). NOS-2, the dimeric, heme-containing, soluble protein whose activity is independent of a rise in intracellular calcium, is variously termed ‘inducible,’ ‘immunologic,’ and ‘macrophage NOS (macNOS).’ Nitric oxide inhibits not only NOS-2 activity but also regulates the level of NOS-2 messenger RNA (mRNA) expression through a mechanism involving NF-(K) B. There is specific evidence for the glial expression of NOS-2 associated with neuronal injury and infection of the CNS and in neurodegenerative and demyelinating diseases. Direct injury in the CNS results in a reactive gliosis, characterized by the induction of the glial fibrillary acidic protein gene and changes in astrocyte morphology.