Inhibition of astroglial NF-kB regulates oligogenesis following spinal cord injury

Astrocytes are taking the center stage in neurotrauma and neurological disease as they appear to play a dominant role in the inflammatory processes associated with these conditions. Previously, we reported that inhibiting nuclear factor kappa B (NF-kB) activation in astrocytes, by using a transgenic mouse model (GFAP-IκBα-dn mice), results in improved functional recovery following spinal cord injury (SCI), with increased white matter preservation and axonal sparing. In the present study we sought to determine whether this improvement, due to inhibiting NF-k-B activation in astrocytes, could be the result of enhanced oligogenesis in our GFAP-IκBα-dn mice. To gain insight into the underlying molecular mechanisms, we performed microarray analysis in naïve and 3 days, 3 and 6 weeks following SCI in GFAP-IκBα-dn and wild type (WT) littermate mice. Surprisingly, we found the largest number of genes differentially regulated between GFAP-IκBα-dn and WT mice 6 weeks post-injury. Interestingly, the data suggested that inhibiting astroglial NF-kB alters the inflammatory environment to support oligogenesis. Furthermore, confirmation of microarray data with qPCR and western blotting analysis and using BrdU labeling along with cell specific immunohistochemistry, confocal microscopy and quantitative cell counts, we demonstrate a significant increase in oligogenesis in GFAP-IκBα-dn following SCI. These studies suggest that therapeutic strategies targeting NF-kB activation in the CNS following SCI may promote oligogenesis and remyelination. Wild type (WT) mice - time points naïve, 3 days, 3 weeks, 6 weeks. Transgenic mice (TG) - time points naïve, 3 days, 3 weeks, 6 weeks.