Abstract

This research program will continue to investigate the regulation of nitric oxide (NO) synthesis in astroglial cells and the role of astrocyte- derived NO in the CNS. During the current funding period the investigators have described the transcriptional induction of a NO synthase (iNOS) in astrocytes in response to endotoxin and cytokines. Experiments planned for the next project period will continue to study the regulation of this inducible NO synthase in vitro and importantly will examine the role of NO in animal neuropathological models. The proposed experiments continue their investigations of the role of astrocyte-derived NO in CNS function, and will specifically examine the conditions that regulate the production of NO mRNA, protein and its activity in vitro and relate these in vitro findings to in vivo conditions in which iNOS is induced.
The specific aims are to: (1) determine the various post receptor mechanisms by which inducing agents activate iNOS gene transcription, (2) investigate whether iNOS and associated enzyme activity can be regulated post-induction by receptor- activated protein kinases, and (3) to examine the expression of astrocyte iNOS mRNA in situ in selected animal neuropathological models of trauma, hyperalgesia, ischemia, and viral infection. These studies should shed light on the role of glial-derived NO in nervous system injuries.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS029226-04A1
Application #
2267462
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1991-08-01
Project End
1999-05-31
Budget Start
1995-06-01
Budget End
1996-05-31
Support Year
4
Fiscal Year
1995
Total Cost
Indirect Cost

  Institution

Name
University of Iowa
Department
Pharmacology
Type
Schools of Medicine
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242

  Publications

Gibson, Claire L; Bath, Philip M W; Murphy, Sean P (2010) G-CSF administration is neuroprotective following transient cerebral ischemia even in the absence of a functional NOS-2 gene. J Cereb Blood Flow Metab 30:739-43
Coughlan, Teresa; Gibson, Claire; Murphy, Sean (2009) Progesterone, BDNF and neuroprotection in the injured CNS. Int J Neurosci 119:1718-40
Gibson, Claire L; Gray, Laura J; Bath, Philip M W et al. (2008) Progesterone for the treatment of experimental brain injury;a systematic review. Brain 131:318-28
Gibson, Claire L; Gray, Laura J; Murphy, Sean P et al. (2006) Estrogens and experimental ischemic stroke: a systematic review. J Cereb Blood Flow Metab 26:1103-13
Constantinescu, Cris S; Tani, Marie; Ransohoff, Richard M et al. (2005) Astrocytes as antigen-presenting cells: expression of IL-12/IL-23. J Neurochem 95:331-40
Coughlan, Teresa; Gibson, Claire; Murphy, Sean (2005) Modulatory effects of progesterone on inducible nitric oxide synthase expression in vivo and in vitro. J Neurochem 93:932-42
Gibson, Claire L; Constantin, Despina; Prior, Malcolm J W et al. (2005) Progesterone suppresses the inflammatory response and nitric oxide synthase-2 expression following cerebral ischemia. Exp Neurol 193:522-30
Willmot, Mark; Gray, Laura; Gibson, Claire et al. (2005) A systematic review of nitric oxide donors and L-arginine in experimental stroke; effects on infarct size and cerebral blood flow. Nitric Oxide 12:141-9
Gibson, Claire L; Bath, Philip M W; Murphy, Sean P (2005) G-CSF reduces infarct volume and improves functional outcome after transient focal cerebral ischemia in mice. J Cereb Blood Flow Metab 25:431-9
Willmot, Mark; Gibson, Claire; Gray, Laura et al. (2005) Nitric oxide synthase inhibitors in experimental ischemic stroke and their effects on infarct size and cerebral blood flow: a systematic review. Free Radic Biol Med 39:412-25

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