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

Savarraj, Jude P.J.; McBride, Devin W.; Park, Eunsu; Hinds, Sarah; Paz, Atzhiry; Gusdon, Aaron M.; Ren, Xuefang; Pan, Sheng; Ahnstedt, Hilda; Colpo, Gabriela Delevati; Kim, Eun‐Hee; Zhao, Zhongming; McCullough, Louise D.; Choi, H. Alex

doi:10.1007/s12028-022-01652-7

Cited by 4 publications

(2 citation statements)

References 41 publications

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“…A role for LRG1 has been reported to be part of the repair mechanism in cerebral damage due to ischaemic injury. Interestingly, high circulating LRG1 levels have been found positively associated with stroke severity and poor functional outcomes ( 104 – 106 ), as well as with poor cognitive impairment and neurological function ( 107 ). In the brain, following ischemic stroke injury a single cell transcriptomics study revealed the emergence of a LRG1-positive endothelial cell subpopulation in the brain infarct area, the expression profile of which suggests its involvement in the complex regulation of angiogenesis, with both pro- and anti-angiogenic factors expressed ( 108 ).…”

Section: Lrg1 Ischemia and Strokementioning

confidence: 99%

The disruptive role of LRG1 on the vasculature and perivascular microenvironment

Dritsoula,

Camilli,

Moss

et al. 2024

Front. Cardiovasc. Med.

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The establishment of new blood vessels, and their subsequent stabilization, is a critical process that facilitates tissue growth and organ development. Once established, vessels need to diversify to meet the specific needs of the local tissue and to maintain homeostasis. These processes are tightly regulated and fundamental to normal vessel and tissue function. The mechanisms that orchestrate angiogenesis and vessel maturation have been widely studied, with signaling crosstalk between endothelium and perivascular cells being identified as an essential component. In disease, however, new vessels develop abnormally, and existing vessels lose their specialization and function, which invariably contributes to disease progression. Despite considerable research into the vasculopathic mechanisms in disease, our knowledge remains incomplete. Accordingly, the identification of angiocrine and angiopathic molecules secreted by cells within the vascular microenvironment, and their effect on vessel behaviour, remains a major research objective. Over the last decade the secreted glycoprotein leucine-rich α-2 glycoprotein 1 (LRG1), has emerged as a significant vasculopathic molecule, stimulating defective angiogenesis, and destabilizing the existing vasculature mainly, but not uniquely, by altering both canonical and non-canonical TGF-β signaling in a highly cell and context dependent manner. Whilst LRG1 does not possess any overt homeostatic role in vessel development and maintenance, growing evidence provides a compelling case for LRG1 playing a pleiotropic role in disrupting the vasculature in many disease settings. Thus, LRG1 has now been reported to damage vessels in various disorders including cancer, diabetes, chronic kidney disease, ocular disease, and lung disease and the signaling processes that drive this dysfunction are being defined. Moreover, therapeutic targeting of LRG1 has been widely proposed to re-establish a quiescent endothelium and normalized vasculature. In this review, we consider the current status of our understanding of the role of LRG1 in vascular pathology, and its potential as a therapeutic target.

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Section: Lrg1 Ischemia and Strokementioning

confidence: 99%

The disruptive role of LRG1 on the vasculature and perivascular microenvironment

Dritsoula,

Camilli,

Moss

et al. 2024

Front. Cardiovasc. Med.

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“…One-third of the patients usually die at the time, and the other one-third develop permanent disability, which seriously affects the patient's quality of life. [1][2][3] Studies 4,5 have found that early brain injury (EBI) is one of the pivotal factors causing this outcome after SAH. EBI involves a variety of physiological disorders, including neuroinflammatory injury, blood-brain barrier disruption, nerve cell apoptosis, etc.…”

Section: Introductionmentioning

confidence: 99%

NAD-Dependent Protein Deacetylase Sirtuin-1 Mediated Mitophagy Regulates Early Brain Injury After Subarachnoid Hemorrhage

Wang,

Lin

2024

JIR

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Background This study focuses on the role of SIRT1 in neuroinflammation caused by early brain injury (EBI) after subarachnoid hemorrhage (SAH), and explores its mechanism in mitophagy after SAH. Methods C57BL/6J mice and primary microglia SAH in vivo and in vitro models were constructed to explore the expression level of SIRT1 in neuroinflammation after SAH. Subsequently, the brain edema content, blood–brain barrier (BBB) damage and neurological function scores of the mice were observed after using the SIRT1 inhibitor EX-527. q-PCR and Western blot were used to detect relevant genes and proteins, and enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of IL-6, IL-1β, and TNF-α inflammatory factors. Immunofluorescence staining was used to observe the positive level of SIRT1 and the degree of mitochondria-lysosome fusion, and transmission electron microscopy was used to observe mitochondrial damage and autophagosome levels. Results In in vivo and in vitro experiments, we found that SIRT1 expression increased after SAH, and neurological deficits, brain edema, and blood–brain barrier damage after SAH were aggravated. Inhibiting SIRT1 further aggravates the aforementioned damage. In addition, EX-527 can also inhibit the level of mitophagy and aggravate neuroinflammation after SAH. Conclusion Our results indicated that SIRT1 promotes mitophagy and alleviates neuroinflammation after SAH.

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Cerebrospinal Fluid Leucine Rich Alpha-2 Glycoprotein in Children with Tubercular Meningitis with their Diagnostic and Prognostic Significance: A Prospective Study: Correspondence

Finsterer

2024

Indian J Pediatr

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

Cited by 4 publications

References 41 publications

The disruptive role of LRG1 on the vasculature and perivascular microenvironment

The disruptive role of LRG1 on the vasculature and perivascular microenvironment

NAD-Dependent Protein Deacetylase Sirtuin-1 Mediated Mitophagy Regulates Early Brain Injury After Subarachnoid Hemorrhage

Cerebrospinal Fluid Leucine Rich Alpha-2 Glycoprotein in Children with Tubercular Meningitis with their Diagnostic and Prognostic Significance: A Prospective Study: Correspondence

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