Preliminary results in the analysis of the immune response after aneurysmal subarachnoid hemorrhage
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...
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| description | 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. |
| doi_str_mv | 10.1038/s41598-020-68861-y |
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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.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-020-68861-y</identifier><identifier>PMID: 32678268</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/250 ; 631/250/127 ; 631/250/2152 ; 631/250/2504 ; 631/250/256 ; 631/250/262 ; 631/250/98 ; 692/617 ; 692/617/375 ; Adaptive Immunity ; Adult ; Aged ; Aged, 80 and over ; Aneurysm ; Aneurysm, Ruptured - complications ; Aneurysms ; Angiography ; Biomarkers ; CD3 antigen ; CD45 antigen ; CD8 antigen ; Cerebrospinal fluid ; Cognition ; Computed tomography ; Cytokines - metabolism ; Enzyme-linked immunosorbent assay ; Female ; Flow cytometry ; Gelatinase B ; Hemorrhage ; Humanities and Social Sciences ; Humans ; Immune response ; Immunity ; Immunity, Innate ; Immunohistochemistry ; Inflammation ; Inflammation Mediators ; Lymphocytes ; Male ; Microglia ; Middle Aged ; multidisciplinary ; Neuroimaging ; Perfusion ; Peripheral blood ; Science ; Science (multidisciplinary) ; Subarachnoid hemorrhage ; Subarachnoid Hemorrhage - etiology ; Subarachnoid Hemorrhage - metabolism ; Subarachnoid Hemorrhage - pathology ; T-Lymphocyte Subsets - immunology ; T-Lymphocyte Subsets - metabolism ; T-Lymphocyte Subsets - pathology ; Variance analysis ; Vascular endothelial growth factor ; Vasoconstriction ; Vasospasm, Intracranial - etiology ; Vasospasm, Intracranial - metabolism</subject><ispartof>Scientific reports, 2020-07, Vol.10 (1), p.11809-11809, Article 11809</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). 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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. 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Roa, Jorge A.</au><au>Sarkar, Deepon</au><au>Zanaty, Mario</au><au>Ishii, Daizo</au><au>Lu, Yongjun</au><au>Karandikar, Nitin J.</au><au>Hasan, David M.</au><au>Ortega, Sterling B.</au><au>Samaniego, Edgar A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Preliminary results in the analysis of the immune response after aneurysmal subarachnoid hemorrhage</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2020-07-16</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>11809</spage><epage>11809</epage><pages>11809-11809</pages><artnum>11809</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32678268</pmid><doi>10.1038/s41598-020-68861-y</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 631/250 631/250/127 631/250/2152 631/250/2504 631/250/256 631/250/262 631/250/98 692/617 692/617/375 Adaptive Immunity Adult Aged Aged, 80 and over Aneurysm Aneurysm, Ruptured - complications Aneurysms Angiography Biomarkers CD3 antigen CD45 antigen CD8 antigen Cerebrospinal fluid Cognition Computed tomography Cytokines - metabolism Enzyme-linked immunosorbent assay Female Flow cytometry Gelatinase B Hemorrhage Humanities and Social Sciences Humans Immune response Immunity Immunity, Innate Immunohistochemistry Inflammation Inflammation Mediators Lymphocytes Male Microglia Middle Aged multidisciplinary Neuroimaging Perfusion Peripheral blood Science Science (multidisciplinary) Subarachnoid hemorrhage Subarachnoid Hemorrhage - etiology Subarachnoid Hemorrhage - metabolism Subarachnoid Hemorrhage - pathology T-Lymphocyte Subsets - immunology T-Lymphocyte Subsets - metabolism T-Lymphocyte Subsets - pathology Variance analysis Vascular endothelial growth factor Vasoconstriction Vasospasm, Intracranial - etiology Vasospasm, Intracranial - metabolism |
| title | Preliminary results in the analysis of the immune response after aneurysmal subarachnoid hemorrhage |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T12%3A56%3A28IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Preliminary%20results%20in%20the%20analysis%20of%20the%20immune%20response%20after%20aneurysmal%20subarachnoid%20hemorrhage&rft.jtitle=Scientific%20reports&rft.au=Roa,%20Jorge%20A.&rft.date=2020-07-16&rft.volume=10&rft.issue=1&rft.spage=11809&rft.epage=11809&rft.pages=11809-11809&rft.artnum=11809&rft.issn=2045-2322&rft.eissn=2045-2322&rft_id=info:doi/10.1038/s41598-020-68861-y&rft_dat=%3Cproquest_pubme%3E2424994420%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2424342397&rft_id=info:pmid/32678268&rfr_iscdi=true |