Introduction:
Decreased mortality and improved functional outcome in female compared to male mice after experimental intracerebral hemorrhage (ICH) has been demonstrated. We postulate that sex-specific differences in post-ICH gene expression may provide mechanistic insight.
Methods:
Ten to 12 week old C57/Bl6 male (M) and female in low estrus (LE-F) or high estrous state (HE-F) mice (n=3/group) underwent ICH induction via left intrastriatal collagenase injection. Whole brain samples were collected at baseline, immediately after sham injury and 6 hours after injury. Genome-wide expression profiling was performed with Affymetrix GeneChip Mouse Genome 2.0 to identify genes differentially expressed between baseline and 6 hours in males and females. Probes showing expression levels greater than log2 (10) for all samples were selected for differential analysis. Comparisons were made between baseline and 6-hour time points to determine significant differential gene expression in both sexes. An adjusted p < 0.05 was considered significant.
Results:
A total of 12136 probes qualified for our filtering criteria, representing 9830 genes. Of the genes tested, 119 in M, 76 in LE-F, and 420 in HE-F were expressed differently at 6 hours as compared to baseline. Of these genes, a total of 37 were shared in M and HE-F groups, 32 in M and LE-F groups, and 42 in HE-F and LE-F groups. Several pathways were identified based on the top list of genes in each group comparison, including coagulation and inflammatory mediator signaling.
Conclusions:
Sex-specific differential gene expression exists at 6 hours after experimental ICH. Further experiments will be designed to test whether these observed differences in gene expression are associated with outcome after experimental ICH and, thus, may yield novel therapeutic targets for translation into the human disease.
Genome-Wide Analysis of Differential Gene Expression and Splicing in Excitatory Neurons and Interneuron Subtypes
