Production of nitric oxide by glial cells: Regulation and potential roles in the CNS

Abstract

Roles proposed for nitric oxide (NO) in CNS pathophysiology are increasingly diverse and range from intercellular signaling, through necrotic killing of cells and invading pathogens, to the involvement of NO in apoptosis and tissue remodeling. In vitro evidence and observations from experimental animal models of a variety of human neuropathologies, including stroke, indicate that glial cells can produce NO. Regulation of at least one of the NO synthase genes (NOS‐2) in glia has been well described; however, apart from hints emerging out of co‐culture studies and extrapolation based upon the reactivity of NO, we are a long way from identifying functions for glial‐derived NO in the CNS. Although the assumption is that NO is very often cytotoxic, it is evident that NO production does not always equate with tissue damage, and that both the cellular source of NO and the timing of NO production are important factors in terms of its effects. With the development of strategies to transfer or manipulate expression of the NOS genes in specific cells in situ, the ability to deliver NO into the CNS via long‐lived chemical donors, and the emergence of more selective NOS inhibitors, an appreciation of the significance of glial‐derived NO will change. GLIA 29:1–13, 2000. © 2000 Wiley‐Liss, Inc.

Calcitonin gene-related peptide stimulation of nitric oxide synthesis and release from trigeminal ganglion glial cells

“…Recently, studies of CNS diseases have demonstrated the importance of glial cells in the pathogenesis of inflammation and pain (DeLeo and Yezierski, 2001;Meller et al, 1994;Watkins et al, 2001a,b). Activation of glial cells associated with the CNS causes the release of a number of cytokines and chemokines as well as nitric oxide (NO) (Murphy, 2000).…”

Mechanisms Involved in the Remyelinating Effect of Sildenafil

“…As said before NOS-2 is induced under pro-inflammatory conditions, LPC demyelination in organotypic cultures leave axons exposed, myelin debris and microglia activation, characteristics of neuroinflammation (Zhang H. et al 2011). NOS-2 produces higher and longerlasting amounts of NO after induction and can be expressed primarily in microglia and astrocytes cells (Brown and Neher 2010, García 2004, Maarsingh et al 2009, Murphy 2000 suggesting that LPC treatment may be responsible of cGMP and NO increase, which can be in part promoting sildenafil effects.…”

“…It can act as a 24 neurotransmitter/neuromodulator or as an inflammatory response mediator, low concentrations of NO mediate physiological signaling and can also be neuroprotective and it has shown to be essential for synaptic plasticity, control of cerebral blood flow, neurogenesis and synaptogenesis (Manucha 2016, Zhang J. andSnyder 1995). However, in high concentrations is a neuropathological agent responsible for excitotoxic cell death and neuroinflammatory cell damage in many neurological disorders (Duncan and Heales 2005, Manucha 2016, Murphy 2000 .…”

“…In peripheral tissues this enzyme is mainly, but not exclusively, expressed in macrophages. In the CNS, NOS-2 is 25 expressed in microglia and astroglia, and its generation of NO has been implicated in the pathogenesis of various insults as well as in neurological disorders (Brown and Neher 2010, Murphy 2000, Steinert et al 2011. Upregulation of iNOS has been implicated in tissue damage in MS and EAE (Raivich and Banati 2004).…”

Estudo da distribuição da proteína S100b em encéfalo de ratos.

“…Essa situação somente aparece em disfunções do SNC, onde seu conteúdo aumentado é verificado no soro ou no líquor (Aurell et al, 1991;Hu et al, 1996Hu et al, , 1997Murphy, 2000). De fato, S100β não apresenta as mesmas propriedades de GFAP, como marcadora, mas desempenha ação direta sobre diferentes proteínas do citoesqueleto, respectivamente, filamentos intermediários, microtúbulos e GFAP, no interir das glias (Bianchi et al, 1993;Donato et al, 1999;Whitaker-Azmitia, 2001;Donato, 2003).…”