Abstract

Subarachnoid hemorrhage (SAH) patients’ surgery is performed to prevent extravasation of blood into the subarachnoid space. Cerebral vasospasm (CVS; narrowing of cerebral arteries) occurs following SAH and represents a major cause of associated mortality and morbidity. To improve postsurgery care of SAH patients and their prognosis, the ability to predict CVS onset is critical. We report a long noncoding RNA (lncRNA) signature to distinguish SAH patients with CVS from SAH patients without CVS. Cerebrospinal fluid (CSF) was obtained from SAH patients without CVS (n = 10) and SAH patients with CVS (n = 10). lncRNAs ZFAS1 and MALAT1 were significantly upregulated (p < 0.05), whereas lncRNAs LINC00261 and LINC01619 were significantly downregulated in SAH patients with CVS (p < 0.05) compared to SAH patients without CVS. We applied this lncRNA signature to retrospectively predict CVS in SAH patients (n = 38 for SAH patients without CVS, and n = 27 for SAH patients with CVS). The 4-lncRNA signature was found to be predictive in >40% of samples and the 2-lncRNA comprising MALAT1 and LINC01619 accurately predicted CVS in ∼90% cases. These results are initial steps toward personalized management of SAH patients in clinics and provide novel CSF biomarkers that can substantially improve the clinical management of SAH patients.

Highlights

  • Subarachnoid hemorrhage (SAH) is a condition that is marked by bleeding into a subarachnoid space, the area surrounding brain in between the arachnoid membrane and the pia mater.[1,2] It is a condition with a high rate of fatality and permanent disability.[3]

  • Expressed long noncoding RNA (lncRNA) in Pooled Samples We screened for differentially expressed lncRNAs in patient samples to be able to predict Cerebral vasospasm (CVS) in SAH patients

  • The screening for lncRNAs was conducted in pooled samples

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Summary

Introduction

Subarachnoid hemorrhage (SAH) is a condition that is marked by bleeding into a subarachnoid space, the area surrounding brain in between the arachnoid membrane and the pia mater.[1,2] It is a condition with a high rate of fatality and permanent disability.[3] The spontaneous occurrence of SAH is about one in 10,000 individuals per year, and the risk includes factors, such as high blood pressure, family history, smoking, etc.[1] A population study in China recruited 512,891 adults (41% men and 59% women) to study the occurrence and risk factors for SAH.[4] It found an annual incidence rate of 12.9 per 100,000 individuals or 1.29 per 10,000 individuals. The incidence of SAH in China is quite comparable to the numbers in Western countries. The Chinese study found a connection between higher blood pressure and SAH—an average of 10 mmHg higher systolic blood pressure and an average of 5 mmHg higher diastolic blood pressure in individuals suffering with SAH.[4]

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