Delayed changes in the transcriptomic profile of cerebral arteries in a rat model of subarachnoid hemorrhage

Abstract

Aneurismal subarachnoid hemorrhage (aSAH) is a neurovascular disease characterized by blood released into the subarachnoid space due to rupture of the cerebral arteries. After the onset of bleeding, secondary associated vasospasm (VSP) remains a dramatic side effect that causes severe comorbidities. We analyzed alterations in the expression profiles of arteries from a rat model of SAH using microarray and bioinformatics approaches. A single injection autologous blood rat model, previously characterized in our laboratory, was used. We performed a total RNA extraction and a microarray analysis of cerebral arteries from animals 7 days after surgery to study the delayed transcriptional changes induced by SAH. To assess the functional relationship between differently expressed genes, we run a combination of gene enrichment tools: GSEA, ClueGO, and ClusterProfiler. Our results showed that in SAH animals, the gene sets related to inflammation and immune system activation were up-regulated; genes related to the pathways involved in the regulation of muscle contraction had their expression disturbed; and the gene categories associated with DNA damage and repair were overrepresented. In conclusion, our results suggest that, after the SAH insult, multiple mechanisms, rather than a single cause, are activated at the same time in the cerebral vessels to trigger vascular alterations.