Activation of NF-κB mediates astrocyte swelling and brain edema in traumatic brain injury

Arumugam R. Jayakumar, Xiao Y. Tong, Roberto Ruiz-Cordero, Amade Bregy, John R Bethea, Helen M. Bramlett, Michael D. Norenberg

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Brain edema and associated increased intracranial pressure are major consequences of traumatic brain injury (TBI). While astrocyte swelling (cytotoxic edema) represents a major component of the brain edema in the early phase of TBI, its mechanisms are unclear. One factor known to be activated by trauma is nuclear factor-κB (NF-κB). Because this factor has been implicated in the mechanism of cell swelling/brain edema in other neurological conditions, we examined whether NF-κB might also be involved in the mediation of post-traumatic astrocyte swelling/brain edema. Here we show an increase in NF-κB activation in cultured astrocytes at 1 and 3h after trauma (fluid percussion injury, FPI), and that BAY 11-7082, an inhibitor of NF-κB, significantly blocked the trauma-induced astrocyte swelling. Increased activities of nicotinamide adenine dinucleotide phosphate-oxidase and the Na+, K+, 2Cl- cotransporter were also observed in cultured astrocytes after trauma, and BAY 11-7082 reduced these effects. We also examined the role of NF-κB in the mechanism of cell swelling by using astrocyte cultures derived from transgenic (Tg) mice with a functional inactivation of astrocytic NF-κB. Exposure of cultured astrocytes from wild-type mice to in vitro trauma (3h) caused a significant increase in cell swelling. By contrast, traumatized astrocyte cultures derived from NF-κB Tg mice showed no swelling. We also found increased astrocytic NF-κB activation and brain water content in rats after FPI, while BAY 11-7082 significantly reduced such effects. Our findings strongly suggest that activation of astrocytic NF-κB represents a key element in the process by which cytotoxic brain edema occurs after TBI.

Original languageEnglish (US)
Pages (from-to)1249-1257
Number of pages9
JournalJournal of neurotrauma
Volume31
Issue number14
DOIs
StatePublished - Jul 15 2014

Keywords

  • Astrocyte swelling
  • NF-jB
  • Transgenic mice
  • Traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology

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