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Accepted (AM)Open Access (License Unspecified), Open
Journal article
Transgenic inhibition of astroglial NF-kappa B leads to increased axonal sparing and sprouting following spinal cord injury
Journal of neurochemistry, v 110(2), pp 765-778
01 Jul 2009
PMID: 19522780
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
We previously showed that Nuclear Factor kappa B (NF-kappa B) 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-kappa B would create a more permissive environment for axonal sprouting and regeneration. We induced both contusive and complete transection SCI in GFAP-Inhibitor of kappa B-dominant negative (GFAP-I kappa B alpha-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-I kappa B alpha-dn mice. Higher numbers of FG-labeled neurons were detected immediately rostral to the lesion in GFAP-I kappa B alpha-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-kappa B 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-I kappa B alpha-dn mice.
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Details
- Title
- Transgenic inhibition of astroglial NF-kappa B leads to increased axonal sparing and sprouting following spinal cord injury
- Creators
- Roberta Brambilla - University of MiamiAndres Hurtado - Kennedy Krieger InstituteTrikaldarshi Persaud - University of MiamiKim Esham - University of MiamiDamien D. Pearse - University of MiamiMartin Oudega - University of PittsburghJohn R. Bethea - University of Miami
- Publication Details
- Journal of neurochemistry, v 110(2), pp 765-778
- Publisher
- Wiley
- Number of pages
- 14
- Grant note
- NS051709 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01NS051709 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) Miami Project to Cure Paralysis
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology; College of Arts and Sciences; Drexel University
- Web of Science ID
- WOS:000267426700030
- Scopus ID
- 2-s2.0-67649506550
- Other Identifier
- 991020100064704721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Neurosciences