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POTENTIAL ROLE OF CIRCULATING EXTRACELLULAR VESICLES IN RECOVERY AFTER INTRACEREBRAL HEMORRHAGE

ABSTRACT: The aim is to evaluate the potential role of circulating exosomes in endogenous mechanisms of cerebral repair after an intracerebral haemorrhage (ICH). We designed a a prospective observational study including patients suffering ICH. EVs were isolated from blood samples at 24 hours and 7 days after onset of symptoms. After a 6-month follow up period, patients were dichotomized in poor and good outcome, defining good outcome as an improvement of >10 points or >50% in NIHSS score and a modified Rankin Score 0-2. Protein cargo was analysed by quantitative mass spectrometry and the changes over time were compared according to outcomes.

INSTRUMENT(S): TripleTOF 6600

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Extracellular Vesicle, Blood Serum

DISEASE(S): Intracerebral Hemorrhage

SUBMITTER: Susana Bravo

LAB HEAD: Susana Bravo

PROVIDER: PXD048138 | Pride | 2025-04-13

REPOSITORIES: Pride

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Project description:Introduction: Intracerebral hemorrhage (ICH) is a severe neurological disorder with no proven treatment. microRNA (miRNA) are short, noncoding nucleic acids that are critical regulators gene expression and promising novel therapeutic targets. Our prior research of mRNA-seq in swine demonstrated that ICH increased inflammatory gene expression within six hours of onset. We now present findings from an integrated analysis of miRNA-seq and mRNA-seq in peripheral blood mononuclear cells (PBMCs) from swine ICH. We tested the hypothesis that ICH would induce miRNA within six hours and that differentially expressed (DE) inflammatory genes would be targets of the DE miRNA. Methods: In 10 pigs, one PBMC sample was collected immediately prior to ICH induction and a second six hours later; miRNA-seq and mRNA-seq were performed. To determine the miRNA that primarily regulated the DE mRNA, an aggregate score was calculated for each miRNA of interest that incorporated the combined summary statistics of its DE target mRNA. Networks of molecular interactions were generated for the target mRNA and the combined miRNA/target mRNA. Results: A total of 227 miRNA were identified with alignment to the Sus scrofa (swine) genome, and 46 were DE (FDR <0.05). When analyzed with the aggregate scoring calculation, the miRNA that were most essential for regulating the DE mRNA included the following, all of which were downregulated post-ICH: miR-29a, miR-29b, miR-31, miR-34c, miR-125a, miR-132, miR-142, miR-150, miR-151a, miR-181a, and miR-186. A highly connected network of interactions was generated from these miRNA and their target mRNA. Conclusion: ICH strongly induced numerous miRNA/mRNA targets in swine PBMCs within six hours of onset. To our knowledge, this is the first integrated analysis of miRNA-seq and mRNA-seq in any study of ICH and the first report of miRNA in swine ICH. Further research is needed to determine whether these miRNA are potential therapeutic targets, including analyzing interventions such as miRNA overexpression or inhibition

			Action	DRS
	24h_00001.wiff	Wiff
	24h_00001.wiff.scan	Wiff
	24h_000010.wiff	Wiff
	24h_000010.wiff.scan	Wiff
	24h_000011.wiff	Wiff

Dataset Information

POTENTIAL ROLE OF CIRCULATING EXTRACELLULAR VESICLES IN RECOVERY AFTER INTRACEREBRAL HEMORRHAGE

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