Dataset Information

Substantially elevated serum glutamate and CSF GOT-1 levels associated with cerebral ischemia and poor neurological outcomes in subarachnoid hemorrhage patients.

ABSTRACT: Brain injury and cerebral vasospasm during the 14 days after the subarachnoid hemorrhage (SAH) are considered the leading causes of poor outcomes. The primary injury induces a cascade of events, including increased intracranial pressure, cerebral vasospasm and ischemia, glutamate excitotoxicity, and neuronal cell death. The objective of this study was to monitor the time course of glutamate, and associated enzymes, such as glutamate-oxaloacetate transaminase (GOT1), glutamate-pyruvate transaminase (GPT) in cerebrospinal fluid (CSF) and serum, shortly after SAH, and to assess their prognostic value. A total of 74 participants participated in this study: 45 participants with SAH and 29 controls. Serum and CSF were sampled up to 14 days after SAH. SAH participants' clinical and neurological status were assessed at hospitalization, at discharge from the hospital, and 3 months after SAH. Furthermore, a logistic regression analysis was carried out to evaluate the ability of GOT1 and glutamate levels to predict neurological outcomes. Our results demonstrated consistently elevated serum and CSF glutamate levels after SAH. Furthermore, serum glutamate level was significantly higher in patients with cerebral ischemia and poor neurological outcome. CSF GOT1 was significantly higher in patients with uncontrolled intracranial hypertension and cerebral ischemia post-SAH, and independently predicted poor neurological outcomes.

SUBMITTER: Snider S

PROVIDER: S-EPMC10066256 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Substantially elevated serum glutamate and CSF GOT-1 levels associated with cerebral ischemia and poor neurological outcomes in subarachnoid hemorrhage patients.

Snider Silvia S Albano Luigi L Gagliardi Filippo F Comai Stefano S Roncelli Francesca F De Domenico Pierfrancesco P Pompeo Edoardo E Panni Pietro P Bens Nicole N Calvi Maria Rosa MR Mortini Pietro P Ruban Angela A

Scientific reports 20230331 1

Brain injury and cerebral vasospasm during the 14 days after the subarachnoid hemorrhage (SAH) are considered the leading causes of poor outcomes. The primary injury induces a cascade of events, including increased intracranial pressure, cerebral vasospasm and ischemia, glutamate excitotoxicity, and neuronal cell death. The objective of this study was to monitor the time course of glutamate, and associated enzymes, such as glutamate-oxaloacetate transaminase (GOT1), glutamate-pyruvate transamina ...[more]

PMID: 37002262

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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

Substantially elevated serum glutamate and CSF GOT-1 levels associated with cerebral ischemia and poor neurological outcomes in subarachnoid hemorrhage patients.

Publications

Substantially elevated serum glutamate and CSF GOT-1 levels associated with cerebral ischemia and poor neurological outcomes in subarachnoid hemorrhage patients.

Similar Datasets

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