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Neurocritical Care
Published in: Neurocritical Care 3/2023

28-12-2022 | Subarachnoid Hemorrhage | Original Work

Leucine-Rich Alpha-2-Glycoprotein 1 is a Systemic Biomarker of Early Brain Injury and Delayed Cerebral Ischemia After Subarachnoid Hemorrhage

Authors: Jude P. J. Savarraj, Devin W. McBride, Eunsu Park, Sarah Hinds, Atzhiry Paz, Aaron Gusdon, Ren Xuefang, Sheng Pan, Hilda Ahnstedt, Gabriela Delevati Colpo, Eunhee Kim, Zhongming Zhao, Louise McCullough, Huimahn Alex Choi

Published in: Neurocritical Care | Issue 3/2023

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Abstract

Background

After subarachnoid hemorrhage (SAH), early brain injury (EBI) and delayed cerebral ischemia (DCI) lead to poor outcomes. Discovery of biomarkers indicative of disease severity and predictive of DCI is important. We tested whether leucine-rich alpha-2-glycoprotein 1 (LRG1) is a marker of severity, DCI, and functional outcomes after SAH.

Methods

We performed untargeted proteomics using mass spectrometry in plasma samples collected at < 48 h of SAH in two independent discovery cohorts (n = 27 and n = 45) and identified LRG1 as a biomarker for DCI. To validate our findings, we used enzyme-linked immunosorbent assay and confirmed this finding in an internal validation cohort of plasma from 72 study participants with SAH (22 DCI and 50 non-DCI). Further, we investigated the relationship between LRG1 and markers of EBI, DCI, and poor functional outcomes (quantified by the modified Rankin Scale). We also measured cerebrospinal fluid (CSF) levels of LRG1 and investigated its relationship to EBI, DCI, and clinical outcomes.

Results

Untargeted proteomics revealed higher plasma LRG1 levels across EBI severity and DCI in both discovery cohorts. In the validation cohort, the levels of LRG1 were higher in the DCI group compared with the non-DCI group (mean (SD): 95 [44] vs. 72 [38] pg/ml, p < 0.05, Student’s t-test) and in study participants who proceeded to have poor functional outcomes (84 [39.3] vs. 72 [43.2] pg/ml, p < 0.05). Elevated plasma LRG1 levels were also associated with markers of EBI. However, CSF levels of LRG1 were not associated with EBI severity or the occurrence of DCI.

Conclusions

Plasma LRG1 is a biomarker for EBI, DCI, and functional outcomes after SAH. Further studies to elucidate the role of LRG1 in the pathophysiology of SAH are needed.
Appendix
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Metadata
Title
Leucine-Rich Alpha-2-Glycoprotein 1 is a Systemic Biomarker of Early Brain Injury and Delayed Cerebral Ischemia After Subarachnoid Hemorrhage
Authors
Jude P. J. Savarraj
Devin W. McBride
Eunsu Park
Sarah Hinds
Atzhiry Paz
Aaron Gusdon
Ren Xuefang
Sheng Pan
Hilda Ahnstedt
Gabriela Delevati Colpo
Eunhee Kim
Zhongming Zhao
Louise McCullough
Huimahn Alex Choi
Publication date
28-12-2022
Publisher
Springer US
Published in
Neurocritical Care / Issue 3/2023
Print ISSN: 1541-6933
Electronic ISSN: 1556-0961
DOI
https://doi.org/10.1007/s12028-022-01652-7

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