Inhibition of astroglial NF-kappaB enhances oligodendrogenesis following spinal cord injury

Background: astrocytes are taking the center stage in neurotrauma and neurological diseases as they appear to play a dominant role in the inflammatory processes associated with these conditions. previously,we reported that inhibiting nf-κb activation in astrocytes,using a transgenic mouse model (gfap-iκbα-dn mice),results in improved functional recovery,increased white matter preservation and axonal sparing following spinal cord injury (sci). in the present study,we sought to determine whether this improvement,due to inhibiting nf-κb activation in astrocytes,could be the result of enhanced oligodendrogenesis in our transgenic mice.methods: to assess oligodendrogenesis in gfap-iκbα-dn compared to wild-type (wt) littermate mice following sci,we used bromodeoxyuridine labeling along with cell-specific immuno-histochemistry,confocal microscopy and quantitative cell counts. to further gain insight into the underlying molecular mechanisms leading to increased white matter,we performed a microarray analysis in naïve and 3 days,3 and 6 weeks following sci in gfap-iκbα-dn and wt littermate mice.results: inhibition of astroglial nf-κb in gfap-iκbα-dn mice resulted in enhanced oligodendrogenesis 6 weeks following sci and was associated with increased levels of myelin proteolipid protein compared to spinal cord injured wt mice. the microarray data showed a large number of differentially expressed genes involved in inflammatory and immune response between wt and transgenic mice. we did not find any difference in the number of microglia/leukocytes infiltrating the spinal cord but did find differences in their level of expression of toll-like receptor 4. we also found increased expression of the chemokine receptor cxcr4 on oligodendrocyte progenitor cells and mature oligodendrocytes in the transgenic mice. finally tnf receptor 2 levels were significantly higher in the transgenic mice compared to wt following injury.conclusions: these studies suggest that one of the beneficial roles of blocking nf-κb in astrocytes is to promote oligodendrogenesis through alteration of the inflammatory environment. © 2013 bracchi-ricard et al.; licensee biomed central ltd.