Inactivation of astroglial NF-κB promotes survival of retinal neurons following ischemic injury

Galina Dvoriantchikova, David Barakat, Roberta Brambilla, Christian Agudelo, Eleut Hernandez, John R. Bethea, Valery I. Shestopalov, Dmitry Ivanov

Research output: Contribution to journalArticle

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Abstract

Reactive astrocytes have been implicated in neuronal loss following ischemic stroke. However, the molecular mechanisms associated with this process are yet to be fully elucidated. In this work, we tested the hypothesis that astroglial NF-κB, a key regulator of inflammatory responses, is a contributor to neuronal death following ischemic injury. We compared neuronal survival in the ganglion cell layer (GCL) after retinal ischemia-reperfusion in wild-type (WT) and in GFAP-IκBα-dn transgenic mice, where the NF-κB classical pathway is suppressed specifically in astrocytes. The GFAP-IκBα-dn mice showed significantly increased survival of neurons in the GCL following ischemic injury as compared with WT littermates. Neuroprotection was associated with significantly reduced expression of pro-inflammatory genes, encoding Tnf-α, Ccl2 (Mcp1), Cxcl10 (IP10), Icam1, Vcam1, several subunits of NADPH oxidase and NO-synthase in the retinas of GFAP-IκBα-dn mice. These data suggest that certain NF-κB-regulated pro-inflammatory and redox-active pathways are central to glial neurotoxicity induced by ischemic injury. The inhibition of these pathways in astrocytes may represent a feasible neuroprotective strategy for retinal ischemia and stroke.

Original languageEnglish (US)
Pages (from-to)175-185
Number of pages11
JournalEuropean Journal of Neuroscience
Volume30
Issue number2
DOIs
StatePublished - Jul 1 2009

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Keywords

  • Astrocytes
  • Inflammation
  • Ischemia
  • Retinal pathology
  • Transgenic mice

ASJC Scopus subject areas

  • Neuroscience(all)

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