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Transgenic inhibition of astroglial NF-κB improves functional recovery in EAE by suppressing chronic neuroinflammation. (50.7)
Journal article   Peer reviewed

Transgenic inhibition of astroglial NF-κB improves functional recovery in EAE by suppressing chronic neuroinflammation. (50.7)

John R Bethea, Roberta Brambilla, Valery I Shestopalov and Scott R Barnum
The Journal of immunology (1950), v 182(1_Supplement), pp 50-50.7
01 Apr 2009
DOI: https://doi.org/10.4049/jimmunol.182.Supp.50.7

Abstract

Abstract In the CNS the transcription factor NF-κB is a key regulator of inflammation and secondary injury processes. Following trauma or disease, the expression of NF-κB-dependent genes is activated, leading to both protective and detrimental effects. Here we show that transgenic inactivation of astroglial NF-κB (GFAP-IκBα-dn mice) resulted in reduced disease severity and improved functional recovery following experimental autoimmune encephalomyelitis (EAE). At the chronic stage of the disease, transgenic mice exhibited an overall higher presence of leukocytes in spinal cord and brain, and a markedly higher percentage of CD8+CD122+ T regulatory cells compared to WT, which correlated with the timing of clinical recovery. We also observed that expression of proinflammatory genes in both spinal cord and cerebellum was delayed and reduced, while the loss of neuronal-specific molecules essential for synaptic transmission was limited compared to WT mice. Furthermore, death of retinal ganglion cells in affected retinas was almost abolished, suggesting the activation of neuroprotective mechanisms. Our data indicate that inhibiting NF-κB in astrocytes results in neuroprotective effects following EAE, directly implicating astrocytes in the pathophysiology of this disease.

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