Plasma and CSF miRNA dysregulations in subarachnoid hemorrhage reveal clinical courses and underlying pathways

Abstract

Background: Subarachnoid hemorrhage (SAH) is fatal and detrimental to quality of life. Clinically, options for monitoring are often limited, potentially missing subtle neurological changes especially in low-grade patients. This article reviewed miRNA dysregulation in SAH and analyzed their functional and clinical relevance. Methods: With adherence to PRISMA guideline, PubMed, EMBASE, GEO and ArrayExpress were searched comprehensively for relevant clinical and animal models. Datasets were analyzed and enriched by experimentally validated targets and multiple databases using R v3.4.2, Ingenuity Pathway Analysis, and miRPath v3.0. Results: Among 1926 search results, 18 studies were screened for full-text assessment. The 8 included studies revealed a marked miRNA dysregulation after SAH. 2 datasets were retrieved. In both serum and CSF, different miRNA profiles were associated with Early Brain Injury, Delayed Cerebral Infarction, vasospasm and prognosis. In CSF, a dramatic restructure of inter-miRNA correlation matrix was observed. Enrichment analysis revealed strong association (1) BBB instability, with adherens, extra-cellular matrix, actin cytoskeleton, integrin, TGF-β Wnt/β-catenin etc; (2) autophagy, with MTORC1, HIF-1, ULK2, and FoxO etc; (3) apoptosis, with PI3K-Akt, p53, and AMPK. We analyzed common miRNAs across SAH and cerebral ischemia. They were related to neuronal differentiation, oxidation stress, apoptosis, angiogenesis, Alzheimer's disease, NMDA-induced calcium influx, excitotoxicity and NO production. Conclusions: Clinical progression of SAH is associated with different miRNA fingerprints. They carry neuro-pathological relevance and can be a potential biomarker which compliments SAH management.