Astrocytes perform important and varied roles in the brain. The location of these glial cells in and around neurons, and their close contact via specialized 'end-feet' with the cerebral vasculature, implicates astrocytes in bi-directional signalling processes. The realization that astrocytes secrete a number of neuroactive amino acids and peptides, together with vasoactive prostanoids and nitrosyl compounds, reinforces this proposition. The long term objective of this research is to study such proposed roles for astrocytes in patho-physiological CNS function; in particular, to determine the significance of their demonstrated ability to synthesize and release a labile, non-prostanoid vasodilator with properties similar to nitric oxide. Well-characteized astroglial cell cultures derived from the neonatal rat forebrain will be used to: 1. Investigate the regulation and control of the enzyme (nitric oxide synthase) predicted to be responsible for the synthesis of the astrocyte-derived relaxing factor. 2. Isolate and purify the enzyme in order to define, and so compare, its biochemical properties with similar enzymes expressed in other cell types of neural and extra-neural origin. This investigation will (a) reveal how synthesis of nitrosyl compounds and their release from astrocytes are regulated, (b) suggest probable interactions between astrocytes, neurons and cells of the vasculature, and (c) lead to predictions about the involvement of astroglial cells in pathologies concerning the cerebral vasculature which can then be experimentally verified.
| 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 |
| 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 |
| Gibson, Claire L; Coughlan, Teresa C; Murphy, Sean P (2005) Glial nitric oxide and ischemia. Glia 50:417-26 |
| Gibson, Claire L; Jones, Nigel C; Prior, Malcolm J W et al. (2005) G-CSF suppresses edema formation and reduces interleukin-1beta expression after cerebral ischemia in mice. J Neuropathol Exp Neurol 64:763-9 |
| 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 |
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