1077. Effects Of Subarachnoid Hemorrhage (SAH) On Mouse Hippocampal Transcriptome.

Authors: Gavin W. Britz, MD, FAANS; Angelique Regnier-Golanov, PhD; Leif Peterson, PhD; Evgueniy Bovshik; Eugene Golanov, MD, PhD (Houston, TX)

Introduction: SAH survivors present long-term neurocognitive impairment with signs of depression and anxiety. These disabilities are sufficiently significant that 44% of the SAH patients are unable to continue with their professional activities. SAH is often followed by general brain atrophy including the temporomesial area. The latter correlates with neurocognitive disorders. These observations are suggestive of hippocampal abnormalities following SAH. While hippocampal abnormalities have been demonstrated, the underlying molecular and cellular mechanisms of neurocognitive outcome remain not completely understood. To identify leading processes in the hippocampus following SAH we used RNA next-generation sequencing to explore the changes in gene expression at the transcriptional level 4 days after SAH. Methods: SAH was induced in anesthetized male C56BL/6J mice by monofilament perforation of the circle of Willis. In sham-operated mice the filament was advanced to the perforation point and withdrawn without puncture. RNA of the whole hippocampus of SAH (n=4), Sham (n=3) and Naïve (n=3) group was extracted using Quiazol, and only RNA with RIN>9.0 were further sequenced. Reads alignment (20-30.10 6 /samples), fragments count and differential expression gene (DEG) analysis were done using Partek Genomic Suite 7.0. Results: Differential expression analysis showed 449 genes significantly altered between Sham and SAH (-1.51.5; p<0.05) with 70% of the DEG being upregulated. Functional analysis (DAVID 6.8) showed an overrepresentation of the DEG in the immune processes, angiogenesis, antigen processing and presentation, and extracellular matrix (false discovery rate [FDR]<10 -4 ). Gene set enrichment analysis with all genes sequenced (GSEA, FDR <0.15) revealed enrichment in complement, astroglial phenotype, interferon gamma and alpha, and depletion in the oligodendrocyte’s phenotype. Conclusion: Prevalent transcriptome changes in the hippocampus in the subacute period (4 days) following SAH suggest that processes related to inflammatory and defense responses mostly localized to the extracellular domain are dominant in the hippocampus following the subarachnoid hemorrhage.