Inhibition of astroglial nuclear factor κB reduces inflammation and improves functional recovery after spinal cord injury

Roberta Brambilla, Valerie Bracchi-Ricard, Wen Hui Hu, Beata Frydel, Annmarie Bramwell, Shaffiat Karmally, Edward J. Green, John R. Bethea

Research output: Contribution to journalArticle

337 Citations (Scopus)

Abstract

In the central nervous system (CNS), the transcription factor nuclear factor (NF)-κB is a key regulator of inflammation and secondary injury processes. After trauma or disease, the expression of NF-κB-dependent genes is highly activated, leading to both protective and detrimental effects on CNS recovery. We demonstrate that selective inactivation of astroglial NF-κB in transgenic mice expressing a dominant negative (dn) form of the inhibitor of κBα under the control of an astrocyte-specific promoter (glial fibrillary acidic protein [GFAP]-dn mice) leads to a dramatic improvement in functional recovery 8 wk after contusive spinal cord injury (SCI). Histologically, GFAP mice exhibit reduced lesion volume and substantially increased white matter preservation. In parallel, they show reduced expression of proinflammatory chemokines and cytokines, such as CXCL10, CCL2, and transforming growth factor-β2, and of chondroitin sulfate proteoglycans participating in the formation of the glial scar. We conclude that selective inhibition of NF-κB signaling in astrocytes results in protective effects after SCI and propose the NF-κB pathway as a possible new target for the development of therapeutic strategies for the treatment of SCI. JEM

Original languageEnglish
Pages (from-to)145-156
Number of pages12
JournalJournal of Experimental Medicine
Volume202
Issue number1
DOIs
StatePublished - Jul 4 2005

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Spinal Cord Injuries
Glial Fibrillary Acidic Protein
Inflammation
Astrocytes
Central Nervous System
Chondroitin Sulfate Proteoglycans
Wounds and Injuries
Transforming Growth Factors
Chemokines
Neuroglia
Transgenic Mice
Cicatrix
Transcription Factors
Cytokines
Genes
Therapeutics

ASJC Scopus subject areas

  • Immunology

Cite this

Inhibition of astroglial nuclear factor κB reduces inflammation and improves functional recovery after spinal cord injury. / Brambilla, Roberta; Bracchi-Ricard, Valerie; Hu, Wen Hui; Frydel, Beata; Bramwell, Annmarie; Karmally, Shaffiat; Green, Edward J.; Bethea, John R.

In: Journal of Experimental Medicine, Vol. 202, No. 1, 04.07.2005, p. 145-156.

Research output: Contribution to journalArticle

Brambilla, Roberta ; Bracchi-Ricard, Valerie ; Hu, Wen Hui ; Frydel, Beata ; Bramwell, Annmarie ; Karmally, Shaffiat ; Green, Edward J. ; Bethea, John R. / Inhibition of astroglial nuclear factor κB reduces inflammation and improves functional recovery after spinal cord injury. In: Journal of Experimental Medicine. 2005 ; Vol. 202, No. 1. pp. 145-156.
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