Abstract
Objectives
Neuroinflammation and secondary injury play a central role in the pathophysiology
of intracerebral hemorrhage. The dual endothelin-1/VEGFsignal-peptide receptor (DEspR)
has been reported to mediate the inflammatory response after acute brain injury in
a rodent model. We performed a pilot study to assess the expression of DEspR on circulating
leukocytes in patients who presented with spontaneous intracerebral hemorrhage (ICH).
Materials and methods
We performed a prospective observational study of patients presenting to two academic
medical centers with ICH. Normal healthy volunteers (NHV) were also recruited for
sample analysis. Whole blood was obtained, and flow cytometry was performed to examine
DEspR expression on neutrophils, monocytes, and lymphocytes.
Results
A total of 19 patients were included in analysis. Median ICH volume was 39 cm3 [IQR 19 cm3, 73 cm3] and median ICH score was 2 [IQR 2, 3]. DEspR expression was more abundant on neutrophils
(median 2.4% [IQR 0.5%, 5.8%], p = 0.0064) and monocytes (median 4.4% [IQR 1.7%, 15.8%], p = 0.003) relative to lymphocytes (median 0.9% [IQR 0.2%, 3.3%]). ICH patients had
higher DEspR expression in all leukocytes relative to NHV (p < 0.05 for all). Among ICH patients, those with a medical history of hypertension
showed higher DEspR expression on neutrophils and monocytes (p = 0.018) compared to those without hypertension.
Conclusions
In this pilot study, DEspR is expressed on circulating neutrophils and monocytes in
humans after ICH, with higher levels of expression in those with hypertension. Future
work in larger cohorts should examine the relationship of DEspR expression with neuroinflammatory
endpoints and long-term outcome.
Keywords
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References
- Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American heart association/American stroke association.Stroke. 2015; 46: 2032-2060
- New mechanistic insights, novel treatment paradigms, and clinical progress in cerebrovascular diseases.Front Aging Neurosci. 2021; 13: 1-15
- Stages of the inflammatory response in pathology and tissue repair after intracerebral hemorrhage.Semin Neurol. 2016; 36: 288-297
- Mannitol and hypertonic saline reduce swelling and modulate inflammatory markers in a rat model of intracerebral hemorrhage.Neurocrit Care. 2018; 29: 253-263
- Organ- and cell-specific immune responses are associated with the outcomes of intracerebral hemorrhage.FASEB J. 2018; 32: 220-229
- TREM2 activation attenuates neuroinflammation and neuronal apoptosis via PI3K/Akt pathway after intracerebral hemorrhage in mice.J Neuroinflammation. 2020; 17: 1-16
- Molecular correlates of hemorrhage and edema volumes following human intracerebral hemorrhage implicate inflammation, autophagy, mRNA splicing, and T cell receptor signaling.Transl Stroke Res. 2020; 12: 754-777
- Inhibition of NOX4/ROS suppresses neuronal and blood-brain barrier injury by attenuating oxidative stress after intracerebral hemorrhage.Front Cell Neurosci. 2020; 14: 1-16
- Confirmation of translatability and functionality certifies the dual endothelin1/VEGFsp receptor (DEspR) protein.BMC Mol Biol. 2016; 17: 1
- Molecular characterization of a dual endothelin-1/angiotensin II receptor.Mol Med. 1998; 4: 1-13
- Anti-DEspR antibody treatment after spontaneous intracerebral hemorrhage (ICH) in ICH-prone dahl salt-sensitive hypertensive rate model increases overall survival, while pre-emptive treatment delays ICH onset.Eur Stroke J. 2021; 6: 9
- Humanized anti-DEspR IgG4S228P antibody increases overall survival in a pancreatic cancer stem cell-xenograft peritoneal carcinomatosis ratnu/nu model.BMC Cancer. 2021; 21: 1-21
- Computed tomographic diagnosis of intraventricular hemorrhage. Etiology and prognosis.Radiology. 1982; 143: 91-96
- The ICH score: a simple, reliable grading scale for intracerebral hemorrhage.Stroke. 2001; 32: 891-897
- Embryonic lethality in dear gene-deficient mice: new player in angiogenesis.Physiol Genom. 2005; 23: 257-268
- DEspR roles in tumor vasculo-angiogenesis, invasiveness, CSC-survival and anoikis resistance: a “common receptor coordinator” paradigm.PLoS One. 2014; 9: 1
- Increased neutrophil-subset associated with severity/mortality in ARDS and COVID19-ARDS expresses the dual endothelin-1/VEGFsignal-Peptide Receptor (DEspR): an actionable therapeutic target.Res Sq. 2021;
- DEspRhigh neutrophils are associated with critical illness in COVID-19.Sci Rep. 2021; 11: 22463
- Role and mechanisms of cytokines in the secondary brain injury after intracerebral hemorrhage.Prog Neurobiol. 2019; 178: 101610
- Targeting secondary injury in intracerebral haemorrhage–perihaematomal oedema.Nat Rev Neurol. 2015; 11: 111-122
- Disability-adjusted life-years associated with intracerebral hemorrhage and secondary injury.JAMA Netw Open. 2021; 4: e2115859
- Peak perihemorrhagic edema correlates with functional outcome in intracerebral hemorrhage.Neurology. 2018; 90: 5-12
- Abstract TP331: Plasma IL-6 Levels are Independently Associated With Functional Outcome and Markers of Secondary Injury in Spontaneous Intracerebral Hemorrhage.Stroke. 2018; 49: 15
- DEspR T/CATAAAA-box promoter variant decreases DEspR transcription and is associated with increased BP in Sardinian males.Physiol Genom. 2011; 43: 1219-1225
Article info
Publication history
Published online: September 01, 2022
Accepted:
July 24,
2022
Received:
March 16,
2022
Identification
DOI: https://doi.org/10.1016/j.jstrokecerebrovasdis.2022.106685
Copyright
© 2022 Elsevier Inc. All rights reserved.