title: The Effects of Hypoxia and Inflammation on Synaptic Signaling in the CNS.
abstract: Normal brain function is highly dependent on oxygen and nutrient supply and when the demand for oxygen exceeds its supply, hypoxia is induced. Acute episodes of hypoxia may cause a depression in synaptic activity in many brain regions, whilst prolonged exposure to hypoxia leads to neuronal cell loss and death. Acute inadequate oxygen supply may cause anaerobic metabolism and increased respiration in an attempt to increase oxygen intake whilst chronic hypoxia may give rise to angiogenesis and erythropoiesis in order to promote oxygen delivery to peripheral tissues. The effects of hypoxia on neuronal tissue are exacerbated by the release of many inflammatory agents from glia and neuronal cells. Cytokines, such as TNF-α, and IL-1β are known to be released during the early stages of hypoxia, causing either local or systemic inflammation, which can result in cell death. Another growing body of evidence suggests that inflammation can result in neuroprotection, such as preconditioning to cerebral ischemia, causing ischemic tolerance. In the following review we discuss the effects of acute and chronic hypoxia and the release of pro-inflammatory cytokines on synaptic transmission and plasticity in the central nervous system. Specifically we discuss the effects of the pro-inflammatory agent TNF-α during a hypoxic event.
authors.affiliation: UCD School of Biomolecular and Biomedical Science, UCD Conway Institute of Biomolecular and Biomedical Research, Belfield, Dublin 4, Ireland. Gatambwa.mukandala@ucdconnect.ie.
authors.forename: Gatambwa
authors.initials: G
authors.lastname: Mukandala
authors.affiliation: UCD School of Biomolecular and Biomedical Science, UCD Conway Institute of Biomolecular and Biomedical Research, Belfield, Dublin 4, Ireland. ronan.tynan@ucdconnect.ie.
authors.forename: Ronan
authors.initials: R
authors.lastname: Tynan
authors.affiliation: UCD School of Biomolecular and Biomedical Science, UCD Conway Institute of Biomolecular and Biomedical Research, Belfield, Dublin 4, Ireland. sinead.lanigan@ucdconnect.ie.
authors.forename: Sinead
authors.initials: S
authors.lastname: Lanigan
authors.affiliation: UCD School of Biomolecular and Biomedical Science, UCD Conway Institute of Biomolecular and Biomedical Research, Belfield, Dublin 4, Ireland. john.oconnor@ucd.ie.
authors.forename: John J
authors.initials: JJ
authors.lastname: O'Connor
keywords: HIF-1α; TNF-α; adenosine; hippocampus; hypoxia; long-term potentiation; prolyl hydroxylase inhibitor