Activation of NF-kappa B Mediates Astrocyte Swelling and Brain Edema in Traumatic Brain Injury

作者：Jayakumar Arumugam R; Tong Xiao Y; Ruiz Cordero Roberto; Bregy Amade; Bethea John R; Bramlett Helen M; Norenberg Michael D^*

来源：Journal of Neurotrauma, 2014, 31(14): 1249-1257.

DOI：10.1089/neu.2013.3169

• astrocyte swelling
• NF-kappa B
• traumatic brain injury
• transgenic mice

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-kappa B (NF-kappa B). Because this factor has been implicated in the mechanism of cell swelling/brain edema in other neurological conditions, we examined whether NF-kappa B might also be involved in the mediation of post-traumatic astrocyte swelling/brain edema. Here we show an increase in NF-kappa B activation in cultured astrocytes at 1 and 3 h after trauma (fluid percussion injury, FPI), and that BAY 11-7082, an inhibitor of NF-kappa B, 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-kappa B in the mechanism of cell swelling by using astrocyte cultures derived from transgenic (Tg) mice with a functional inactivation of astrocytic NF-kappa B. Exposure of cultured astrocytes from wild-type mice to in vitro trauma (3 h) caused a significant increase in cell swelling. By contrast, traumatized astrocyte cultures derived from NF-kappa B Tg mice showed no swelling. We also found increased astrocytic NF-kappa B 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-kappa B represents a key element in the process by which cytotoxic brain edema occurs after TBI.

• 出版日期2014-7-15