Dataset Information

Circulating microRNA Profiles in Acute Spinal Cord Injury: Evidence for Distinct Plasma Signatures Compared with Polytrauma Patients

ABSTRACT: Background: Traumatic spinal cord injury (SCI) is a devastating complication of trauma, causing long-term disability and significant socioeconomic burden. Beyond the primary mechanical insult, secondary injury cascades involving apoptosis, oxidative stress, and inflammation amplify tissue damage. MicroRNAs (miRNAs) regulate these processes at the post-transcriptional level, yet data on circulating miRNAs in human SCI remain scarce. Objective: This study aimed to characterize acute plasma miRNA expression patterns in isolated SCI that may indicate SCI-specific signatures. Methods: Plasma was collected from five SCI patients at admission and 48 h post-injury and five healthy controls (HC) and Next-generation sequencing (NGS) was performed on plasma RNAs. Differentially expressed miRNAs were identified and selected candidate miRNAs were validated by droplet digital PCR (ddPCR) in an expanded cohort of SCI patients, polytrauma patients without neurotrauma (PT), and HC (each n=8). Pathway enrichment and validated target analysis were performed to assess biological relevance of candidate miRNAs. Results: At emergency room admission, 46 miRNAs were differentially expressed in SCI plasma (18 upregulated, 28 downregulated). By 48 h, a global downregulation was observed, with 47 miRNAs significantly decreased compared with HC. ddPCR validation revealed markedly stronger suppression of miR-182-5p, miR-190a-5p, miR-144-5p, and miR-30c-5p expression levels in SCI compared with PT, suggesting a neurogenic rather than trauma-related regulation. Pathway analysis indicated enrichment of mitochondrial oxidative phosphorylation pathways, and target prediction suggested that the identified miRNAs may be linked to neuroprotective and regenerative functions. Conclusion: Our findings demonstrate early and profound alterations in circulating miRNAs after acute SCI. The downregulation of the identified miRNAs may reflect maladaptive changes that promote neuroinflammation and hinder axonal regeneration, although the exact functional consequences remain to be clarified. These data suggest that circulating miRNAs could hold promise as diagnostic and prognostic biomarkers and, potentially, as therapeutic targets to influence secondary injury processes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE309413 | GEO | 2025/10/03

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Purpose: Post-traumatic epilepsy (PTE) is an epilepsy that develops after traumatic brain injury (TBI), and it comprises 10-20% of structural epilepsies and 5% of all epilepsies. The lack of prognostic biomarkers for PTE hinders the development of anti-epileptogenic treatments. In this preclinical multicenter study, plasma samples collected from a rat model of PTE were analyzed by small RNA sequencing to reveal the post-TBI expression profile of circulating microRNAs and to identify potential miRNA biomarkers for PTE development. Methods: The animal experiments were conducted at 3 different study sites: University of Eastern Finland (Finland), Monash University (Australia), and University of California, Los Angeles (USA). Severe TBI was induced in adult male Sprague-Dawley rats by the lateral fluid-percussion injury (LFPI) method. Rats that developed PTE were identified by video-EEG monitoring during the 7th post-injury month (TBI rats with epilepsy, TBIE; TBI rats without epilepsy, TBIN). Small RNA sequencing was conducted with plasma samples collected 48 hours after TBI or sham operation (craniotomy). Following the primary quantification, DESeq2 (v. 1.42.0) was used to identify differentially expressed miRNAs between the experiment groups. Results were further validated in a larger sample cohort by droplet digital PCR (ddPCR). Results: Small RNA sequencing detected a total of 754 miRNAs that were expressed in at least one sample. DESeq2 detected 23 differentially expressed (DE) miRNAs between the TBI and sham groups, 12 between the TBIE and sham groups, and 5 between the TBIN and sham groups. In contrast, no DE miRNAs were detected between the TBIE and TBIN groups. From the list of 23 DE miRNAs between the TBI and sham groups, 3 upregulated miRNAs (rno-miR-183-5p, rno-miR-323-3p, and miR-434-3p) were selected for further ddPCR validation. The list of miRNAs for validation was further complemented by 4 miRNAs (rno-miR-9a-3p, rno-miR-124-3p, rno-miR-132-3p, and rno-miR-212-3p), which were not differentially expressed in the DESeq2 analysis, but which we have previously detected to be acutely upregulated in TBI rat plasma. The validation was conducted with samples from the entire EpiBioS4Rx cohort [26 baseline samples, 45 sham, 164 TBI (32 TBIE, 132 TBIN)]. DdPCR analysis revealed that all 7 investigated miRNAs were upregulated in the TBI rats compared with the sham controls. No differences were detected between the rats with (TBIE) or without epilepsy (TBIN). In contrast, TBIE rats that had seizure clusters (severe PTE) had lower levels of plasma miR-212-3p compared with other TBI rats. Furthermore, elastic net regularized logistic regression (glmnet) analysis identified miR-212-3p and miR-132-3p as the optimal set to differentiate TBIE rats with seizure clusters from other TBI rats. Conclusions: The profile of circulating plasma microRNAs differed between TBI rats and sham controls. MiR-212-3p alone or in combination with miR-132-3p showed potential as prognostic biomarkers for development of severe PTE.

Dataset Information

Circulating microRNA Profiles in Acute Spinal Cord Injury: Evidence for Distinct Plasma Signatures Compared with Polytrauma Patients

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets