Multiple classes of small RNAs (sRNAs) are expressed in the blood and are 
involved in the regulation of pivotal cellular processes. We aimed to elucidate 
the expression patterns and functional roles of sRNAs in the systemic response 
to intracranial aneurysm (IA) rupture. We used next-generation sequencing to 
analyze the expression of sRNAs in patients in the acute phase of IA rupture 
(first 72 h), in the chronic phase (3-15 months), and controls. The patterns of 
alterations in sRNA expression were analyzed in the context of clinically 
relevant information regarding the biological consequences of IA rupture. We 
identified 542 differentially expressed sRNAs (108 piRNAs, 99 rRNAs, 90 miRNAs, 
43 scRNAs, 36 tRNAs, and 32 snoRNAs) among the studied groups with notable 
differences in upregulated and downregulated sRNAs between the groups and sRNAs 
categories. piRNAs and rRNAs showed a substantial decrease in RNA abundance that 
was sustained after IA rupture, whereas miRNAs were largely upregulated. 
Downregulated sRNA genes included piR-31080, piR-57947, 5S rRNA, LSU-rRNA, and 
SSU-rRNA s. Remarkable enrichment in the representation of transcription factor 
binding sites was revealed in genomic locations of the regulated sRNA. We found 
strong overrepresentation of glucocorticoid receptor, retinoid x receptor alpha, 
and estrogen receptor alpha binding sites at the locations of downregulated 
piRNAs, tRNAs, and rRNAs. This report, although preliminary and largely 
proof-of-concept, is the first to describe alterations in sRNAs abundance levels 
in response to IA rupture in humans. The obtained results indicate novel 
mechanisms that may constitute another level of control of the inflammatory 
response. KEY MESSAGES: A total of 542 sRNAs were differentially expressed after 
aneurysmal SAH comparing with controls piRNAs and rRNAs were upregulated and 
miRNAs were downregulated after IA rupture The regulated sRNA showed an 
enrichment in the representation of some transcription factor binding sites 
piRNAs, tRNAs, and rRNAs showed an overrepresentation for GR, RXRA, and ERALPHA 
binding sites.