Background and Aims: Surgical management of intracerebral (ICH) remains controversial due to unclear benefit. In this study, we analyzed temporal changes in expression of proinflammatory and anti-inflammatory survival genes to discern the molecular differences between favorable and unfavorable outcomes after surgery. Methods: Venous blood collected in Paxgene Blood RNA from ICH patients before surgery at ‘early’ (Day 0-2) and at ‘delayed’ (Day 3-5) timepoints. Extracted total RNA was used for real-time Taqman PCR analysis for anti-inflammatory, survival genes superoxide dismutase 1(SOD1), COX-2, IL-10, peroxisome proliferator activated receptor gamma (PPARG), TGF-B1, and IL-10. The pro-inflammatory genes included arginase-1 (ARG1), TNF, IL-1B, monocyte/macrophage activity markers (CD36, CD163) and NF-kB members (NFKB1, NFKB2, RELA, RELB, REL, NFKBIA). Relative fold changes were determined after normalizing to GAPDH. 90-day Modified Rankin Score (mRS) were collected and classified as favorable, mRS 0-3 (n=4) and unfavorable, mRS 4-6 (n=8). Statistical analysis was carried out by Welch’s ANOVA test (p<0.05). Results: Mean age was 56.25yrs (SD 19.7). ICH location was 10 deep nuclei (thalamus or basal ganglia), 1 cerebellum, and 1 lobar. ICH volume was lower in the mRS 0-3 group (24.15ml SD21.2 vs 35.8ml SD 31.7 p=0.68). All patients had a decompressive hemicraniectomy and 7 included hematoma evacuation. Overall, the NFkB family gene expression was increased at ‘delayed’ relative to the early time points in both groups. However, RELB expression was significantly higher at the early time point of mRS 0-3 compared to mRS 4-6 group. Expression of ARG1, SOD1, COX2, IL-1B, IL-10, TGF-B1, PPARG and CD36 increased significantly at the delayed compared to the early time point. In the unfavorable outcome group (mRS 4-6), TNF expression increased significantly at the delayed timepoints compared to mRS 0-3 which was unchanged. Conclusions: The studied genes were highly expressed and differed significantly between time points. TNF was significantly expressed at the delayed time point in the mRS 4-6 group but unchanged in the mRS 0-3 group. Further studies will explore the role of TNF and related genes in patient selection and outcomes for surgical management of ICH.
Introduction: microRNAs (miRNAs) profiles in plasma and cerebrospinal fluid change in relation to cerebrovascular diseases and may serve as biomarkers or therapeutic targets of intracerebral hemorrhage (ICH). In this study, we examined the expression of novel and previously unreported miRNAs in ICH in plasma and cerebrospinal fluid (CSF) identified from miRNA sequencing. Methods: Patients with acute spontaneous ICH (n=8) were consented and peripheral whole blood were collected within 48 hours of ICH onset and processed for plasma and peripheral blood mononuclear cells (PBMC). CSF was obtained from an external ventricular drain (EVD). Six novel miRNAs were selected from miR-Seq analysis and further validated for their expression in ICH plasma/CSF, PBMC RNA and normal control plasma/CSF. Total RNA was used for real-time PCR validation of novel miRNAs using custom locked-nucleic acid (LNA) assay. Demographic and clinical data were collected. Results: miRNA-seq comparison between ICH plasma and CSF identified 19 and 30 differentially expressed miRNA (p<0.05), of which 9 and 7 novel miRNAs were identified in plasma and CSF, respectively. PC-5p-218_26568 was identified in ICH CSF, ICH PBMC and weakly in ICH plasma and normal plasma, but not in normal CSF. PC-5p-585_8337 was identified in ICH CSF and plasma, but not in normal CSF, plasma or ICH PBMC. PC-3p-4244_570 was found in CSF and plasma ICH patients and normal controls, exhibiting a 4-fold and 11-fold higher in ICH CSF and plasma than normal controls. It was also identified in ICH PBMC. PC-5p-1115_3460 was detected in normal plasma but not in ICH plasma, whereas PC-5p-6497_338 was found in ICH plasma but not in normal plasma and CSF. Lastly, PC-3p-3144_857 was found in ICH plasma and ICH PBMC and not in CSF. Conclusion: We identified distinct differences in miRNAs expression in healthy and ICH plasma and CSF. Further studies are underway on the gene targets and utility of these miRNAs as therapeutic targets or biomarkers of ICH.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.