Preliminary results in the analysis of the immune response after aneurysmal subarachnoid hemorrhage

Jorge A Roa; Deepon Sarkar; Mario Zanaty; Daizo Ishii; Yongjun Lu; Nitin J Karandikar; David M Hasan; Sterling B Ortega; Edgar A Samaniego

doi:10.1038/s41598-020-68861-y

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Preliminary results in the analysis of the immune response after aneurysmal subarachnoid hemorrhage

Journal article

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Peer reviewed

Preliminary results in the analysis of the immune response after aneurysmal subarachnoid hemorrhage

Jorge A Roa, Deepon Sarkar, Mario Zanaty, Daizo Ishii, Yongjun Lu, Nitin J Karandikar, David M Hasan, Sterling B Ortega and Edgar A Samaniego

Scientific reports, Vol.10(1), pp.11809-11809

07/16/2020

DOI: 10.1038/s41598-020-68861-y

PMCID: PMC7367262

PMID: 32678268

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Abstract

Cerebral vasospasm (VSP) is a common phenomenon after aneurysmal subarachnoid hemorrhage (aSAH) and contributes to neurocognitive decline. The natural history of the pro-inflammatory immune response after aSAH has not been prospectively studied in human cerebrospinal fluid (CSF). In this pilot study, we aimed to identify specific immune mediators of VSP after aSAH. Peripheral blood (PB) and CSF samples from patients with aSAH were prospectively collected at different time-points after hemorrhage: days 0-1 (acute); days 2-4 (pre-VSP); days 5-9 (VSP) and days 10 + (post-VSP peak). Presence and severity of VSP was assessed with computed tomography angiography/perfusion imaging and clinical examination. Cytokine and immune mediators' levels were quantified using ELISA. Innate and adaptive immune cells were characterized by flow cytometry, and cell counts at different time-points were compared with ANOVA. Confocal immunostaining was used to determine the presence of specific immune cell populations detected in flow cytometry. Thirteen patients/aneurysms were included. Five (38.5%) patients developed VSP after a mean of 6.8 days from hemorrhage. Flow cytometry demonstrated decreased numbers of CD45+ cells during the acute phase in PB of aSAH patients compared with healthy controls. In CSF of VSP patients, NK cells (CD3-CD161 +) were increased during the acute phase and progressively declined, whereas CD8+CD161+ lymphocytes significantly increased at days 5-9. Microglia cells (CD45dimCD11b +) increased over time after SAH. This increase was particularly significant in patients with VSP. Levels of VEGF and MMP-9 were consistently higher in VSP patients, with the highest difference occurring at the acute phase. Confocal immunostaining demonstrated the presence of CD8+CD161+ lymphocytes in the arterial wall of two unruptured intracranial aneurysms. In this preliminary study, human CSF showed active presence of innate and adaptive immune cells after aSAH. CD8+CD161+ lymphocytes may have an important role in the inflammatory response after aneurysmal rupture and were identified in the aneurysmal wall of unruptured brain aneurysms. Microglia activation occurs 6 + days after aSAH.

Adaptive Immunity

Immunohistochemistry

T-Lymphocyte Subsets - immunology

Vasospasm, Intracranial - etiology

Inflammation Mediators

Cytokines - metabolism

Humans

Middle Aged

Male

Immunity, Innate

Subarachnoid Hemorrhage - pathology

Immunity

Aneurysm, Ruptured - complications

Subarachnoid Hemorrhage - metabolism

T-Lymphocyte Subsets - pathology

T-Lymphocyte Subsets - metabolism

Aged, 80 and over

Biomarkers

Subarachnoid Hemorrhage - etiology

Vasospasm, Intracranial - metabolism

Adult

Female

Aged

Details

Title: Subtitle: Preliminary results in the analysis of the immune response after aneurysmal subarachnoid hemorrhage
Creators: Jorge A Roa - Department of Neurosurgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
Deepon Sarkar - Department of Neurology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
Mario Zanaty - Department of Neurosurgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
Daizo Ishii - Department of Neurosurgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
Yongjun Lu - Department of Neurosurgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
Nitin J Karandikar - Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
David M Hasan - Department of Neurosurgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
Sterling B Ortega - Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
Edgar A Samaniego - Department of Radiology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA. edgarsama@gmail.com
Resource Type: Journal article
Publication Details: Scientific reports, Vol.10(1), pp.11809-11809
DOI: 10.1038/s41598-020-68861-y
PMID: 32678268
PMCID: PMC7367262
NLM abbreviation: Sci Rep
ISSN: 2045-2322
eISSN: 2045-2322
Publisher: England
Grant note: T32 HL007344 / NHLBI NIH HHS
Language: English
Date published: 07/16/2020
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Neurology; Radiology; Critical Care; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Neurosurgery; Otolaryngology
Record Identifier: 9984070705202771

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