The miRNA transcriptome of cerebrospinal fluid in preterm infants reveals the signaling pathways that promote reactive gliosis following cerebral hemorrhage

Introduction Germinal Matrix-Intraventricular Haemorrhage (GM-IVH) is one of the most common neurological complications in preterm infants, which can lead to accumulation cerebrospinal fluid (CSF) and a major cause severe neurodevelopmental impairment infants. However, pathophysiological mechanisms triggered by GM-IVH are poorly understood. Analyzing CSF that accumulates following IVH may allow molecular signaling intracellular communication contributes pathogenesis be elucidated. Growing evidence suggests miRs, due their key role gene expression, have significant utility as new therapeutics biomarkers. Methods The levels 2,083 microRNAs (miRs) 15 samples from 10 infants with were measured using miRNA whole transcriptome sequencing. Gene ontology (GO) miR family analysis used uncover dysregulated signalling then validated vitro human foetal neural progenitor cells treated IVH-CSF. Results Five hundred eighty-seven miRs differentially expressed extracted at least 2 months after injury, compared within first month injury. GO uncovered pathways targeted including MAPK cascade JAK/STAT pathway. Astrogliosis known occur we hypothesized this could abnormal CSF-miR resulting dysregulation pathway – controller astrocyte differentiation. We confirmed treatment IVH-CSF promotes differentiation fetal NPCs effect prevented inhibition. Taken together, our results provide novel insights into CSF/NPCs crosstalk perinatal brain injury reveal targets improve outcomes