Transgenic inhibition of astroglial NF-κB leads to increased axonal sparing and sprouting following spinal cord injury

Roberta Brambilla, Andres Hurtado, Trikaldarshi Persaud, Kim Esham, Damien D. Pearse, Martin Oudega, John R. Bethea

Research output: Contribution to journalArticle

Abstract

We previously showed that Nuclear Factor κB (NF-κB) inactivation in astrocytes leads to improved functional recovery following spinal cord injury (SCI). This correlated with reduced expression of pro-inflammatory mediators and chondroitin sulfate proteoglycans, and increased white matter preservation. Hence we hypothesized that inactivation of astrocytic NF-κB would create a more permissive environment for axonal sprouting and regeneration. We induced both contusive and complete transection SCI in GFAP-Inhibitor of κB-dominant negative (GFAP-IκBα-dn) and wild-type (WT) mice and performed retrograde [fluorogold (FG)] and anterograde [biotinylated dextran amine (BDA)] tracing 8 weeks after injury. Following contusive SCI, more FG-labeled cells were found in motor cortex, reticular formation, and raphe nuclei of transgenic mice. Spared and sprouting BDA-positive corticospinal axons were found caudal to the lesion in GFAP-IκBα-dn mice. Higher numbers of FG-labeled neurons were detected immediately rostral to the lesion in GFAP-IκBα-dn mice, accompanied by increased expression of synaptic and axonal growth-associated molecules. After transection, however, no FG-labeled neurons or BDA-filled axons were found rostral and caudal to the lesion, respectively, in either genotype. These data demonstrated that inhibiting astroglial NF-κB resulted in a growth-supporting terrain promoting sparing and sprouting, rather than regeneration, of supraspinal and propriospinal circuitries essential for locomotion, hence contributing to the improved functional recovery observed after SCI in GFAP-IκBα-dn mice.

Original languageEnglish (US)
Pages (from-to)765-778
Number of pages14
JournalJournal of Neurochemistry
Volume110
Issue number2
DOIs
StatePublished - Jul 2009

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Keywords

  • Anterograde tracing
  • Astrocytes
  • GAP-43
  • Neuroprotection
  • Retrograde tracing
  • Transgenic mice

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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