Strain-dependent variation in the early transcriptional response to CNS injury using a cortical explant system

Background: while it is clear that inbred strains of mice have variations in immunological responsiveness,the influence of genetic background following tissue damage in the central nervous system is not fully understood. a cortical explant system was employed as a model for injury to determine whether the immediate transcriptional response to tissue resection revealed differences among three mouse strains.methods: immunological mrnas were measured in cerebral cortex from sjl/j,c57bl/6j,and balb/cj mice using real time rt-pcr. freshly isolated cortical tissue and cortical sections incubated in explant medium were examined. levels of mrna,normalized to β-actin,were compared using one way analysis of variance with pooled samples from each mouse strain.results: in freshly isolated cerebral cortex,transcript levels of many pro-inflammatory mediators were not significantly different among the strains or too low for comparison. constitutive,baseline amounts of cd74 and antisecretory factor (asf) mrnas,however,were higher in sjl/j and c57bl/6j,respectively. when sections of cortical tissue were incubated in explant medium,increased message for a number of pro-inflammatory cytokines and chemokines occurred within five hours. message for chemokines,il-1α,and cox-2 transcripts were higher in c57bl/6j cortical explants relative to sjl/j and balb/cj. il-1β,il-12/23 p40,and tnf-α were lower in balb/cj explants relative to sjl/j and c57bl/6j. similar to observations in freshly isolated cortex,cd74 mrna remained higher in sjl/j explants. the asf mrna in sjl/j explants,however,was now lower than levels in both c57bl/6j and balb/cj explants.conclusions: the short-term cortical explant model employed in this study provides a basic approach to evaluate an early transcriptional response to neurological damage,and can identify expression differences in genes that are influenced by genetic background. © 2011 graber et al; licensee biomed central ltd.