Dataset Information

Inflammation in delayed ischemia and functional outcomes after subarachnoid hemorrhage.

ABSTRACT:

Background

Inflammatory mechanism has been implicated in delayed cerebral ischemia (DCI) and poor functional outcomes after subarachnoid hemorrhage (SAH). Identification of cytokine patterns associated with inflammation in acute SAH will provide insights into underlying biological processes of DCI and poor outcomes that may be amenable to interventions.

Methods

Serum samples were collected from a prospective cohort of 60 patients with acute non-traumatic SAH at four time periods (ResultsOf the 60 patients enrolled in the study, 14 (23.3%) developed DCI and 16 (26.7%) had poor functional outcomes at 3?months. DCI was associated with increased levels of PDGF-ABBB and CCL5 and decreased levels of IP-10 and MIP-1?. Poor functional outcome was associated with increased levels of IL-6 and MCP-1?. Network analysis identified distinct cytokine clusters associated with DCI and functional outcomes.

Conclusions

Serum cytokine patterns in early SAH are associated with poor functional outcomes and DCI. The significant cytokines primarily modulate the inflammatory response. This supports earlier SAH studies linking inflammation and poor outcomes. In particular, this study identifies novel cytokine patterns over time that may indicate impending DCI.

SUBMITTER: Ahn SH

PROVIDER: S-EPMC6849179 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Publications

Inflammation in delayed ischemia and functional outcomes after subarachnoid hemorrhage.

Ahn Sung-Ho SH Savarraj Jude P J JPJ Parsha Kaushik K Hergenroeder Georgene W GW Chang Tiffany R TR Kim Dong H DH Kitagawa Ryan S RS Blackburn Spiros L SL Choi H Alex HA

Journal of neuroinflammation 20191111 1

<h4>Background</h4>Inflammatory mechanism has been implicated in delayed cerebral ischemia (DCI) and poor functional outcomes after subarachnoid hemorrhage (SAH). Identification of cytokine patterns associated with inflammation in acute SAH will provide insights into underlying biological processes of DCI and poor outcomes that may be amenable to interventions.<h4>Methods</h4>Serum samples were collected from a prospective cohort of 60 patients with acute non-traumatic SAH at four time periods ( ...[more]

PMID: 31711504

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Project description:Delayed cerebral ischemia (DCI) is a common secondary complication and an important cause of disability and mortality among patients who survive aneurysmal subarachnoid hemorrhage (aSAH). Knowledge on DCI pathogenesis, risk factors, and biomarkers are essential for early detection and improved prognosis. To investigate the role of DNA methylation in DCI risk, we conducted an epigenome-wide association study (EWAS) in 68 patients followed up to 1 year after the initial aneurysm rupture. Blood samples were collected within 48 h post hemorrhage and used for DNA methylation profiling at ~ 450k CpG sites. A separate cohort of 175 patients was sequenced for the top CpG sites from the discovery analysis for a replication of the EWAS findings. EWAS did not identify any epigenome-wide significant CpGs. The top signal, cg18031596, was annotated to ANGPT1, a gene with critical functions in angiogenesis after vascular injury. Post hoc power calculations indicated a well-powered discovery analysis for cg18031596. Analysis of the replication cohort showed that four out of the five CpG sites sequenced at the ANGPT1 locus passed a Bonferroni-adjusted significance threshold. In a pooled analysis of the entire sample, three out of five yielded a significant p-value, and the top association signal (p-value = 0.004) was seen for a CpG that was not originally measured in the discovery EWAS. However, four ANGPT1 CpG sites had an opposite effect direction in the replication analysis compared to the discovery EWAS, marking a failure of replication. We carefully examined this observed flip in directions and propose several possible explanations in addition to that it was a random chance that ANGPT1 ranked at the top in the discovery EWAS. We failed to demonstrate a significant and consistent effect of ANGPT1 methylation in DCI risk in two cohorts. Though the replication attempt to weaken the overall support of this gene, given its relevant function and top rank of significance in the EWAS, our results call for future studies of larger aSAH cohorts to determine its relevance for the occurrence of DCI.

Dataset Information

Inflammation in delayed ischemia and functional outcomes after subarachnoid hemorrhage.

Background

Methods

Conclusions

Publications

Inflammation in delayed ischemia and functional outcomes after subarachnoid hemorrhage.

Similar Datasets

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