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Complement Inhibition in Chronic Subdural Hematoma Fluid

Marklund, Niklas LU orcid ; Zolfaghari, Shaian LU orcid ; Westerberg, Gustaf LU ; Ruscher, Karsten LU ; Englund, Elisabet LU orcid and Redebrandt, Henrietta Nittby LU (2024) In Inflammation
Abstract

Background: Emerging data suggest a complex pathophysiology of chronic subdural hematoma (CSDH) to which an inflammatory response might contribute. The complement system is activated in acute traumatic setting, although its role in CSDH is unknown. To investigate the complement system in CSDH pathophysiology, we analyzed blood and hematoma fluid biomarkers, as well as immunohistochemistry of the CSDH membrane and dura. Materials and Methods: We simultaneously collected CSDH fluid and peripheral blood from 20 CSDH patients at the time of surgery. Biopsies of the dura mater and the CSDH capsule were obtained and analyzed by immunohistochemistry for C5b-C9 or C5a deposition. Biomarkers of inflammation and complement activation were... (More)

Background: Emerging data suggest a complex pathophysiology of chronic subdural hematoma (CSDH) to which an inflammatory response might contribute. The complement system is activated in acute traumatic setting, although its role in CSDH is unknown. To investigate the complement system in CSDH pathophysiology, we analyzed blood and hematoma fluid biomarkers, as well as immunohistochemistry of the CSDH membrane and dura. Materials and Methods: We simultaneously collected CSDH fluid and peripheral blood from 20 CSDH patients at the time of surgery. Biopsies of the dura mater and the CSDH capsule were obtained and analyzed by immunohistochemistry for C5b-C9 or C5a deposition. Biomarkers of inflammation and complement activation were analyzed by a 21-multiplex assay, including Adiponectin, Clusterin, Complement factor C9 and CRP. Complement factor C5a was analyzed separately by a commercial R-plex electrochemiluminescence assay. Results: Ten biomarkers differed significantly between peripheral blood and paired CSDH of which two were significantly increased in CSDH fluid (Clusterin and Cystatin C). Eight of the significantly altered biomarkers were significantly decreased in CSDH fluid, including C5a, Complement 9 and Adiponectin. There was no immunoreactivity for C5a or the C5b-C9 membrane attack complex in the dura or CSDH membrane. Conclusions: In CSDH levels of the complement inhibitor Clusterin were increased, whereas levels of C5a and C9 were decreased. Membrane attack complex C5b-C9 was not detected in the membrane or dura surrounding the CSDH. Inhibition of complement could lead to reduced clearance of debris in the CSDH as well as secondary inflammatory reactions.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
Biomarker, Chronic Subdural Hematoma, Complement Factor
in
Inflammation
publisher
Springer
external identifiers
  • pmid:39652217
  • scopus:85211783622
ISSN
0360-3997
DOI
10.1007/s10753-024-02210-3
language
English
LU publication?
yes
id
3e65db3d-a90a-46bf-8980-736c674420ae
date added to LUP
2025-01-31 14:18:20
date last changed
2025-07-05 03:00:48
@article{3e65db3d-a90a-46bf-8980-736c674420ae,
  abstract     = {{<p>Background: Emerging data suggest a complex pathophysiology of chronic subdural hematoma (CSDH) to which an inflammatory response might contribute. The complement system is activated in acute traumatic setting, although its role in CSDH is unknown. To investigate the complement system in CSDH pathophysiology, we analyzed blood and hematoma fluid biomarkers, as well as immunohistochemistry of the CSDH membrane and dura. Materials and Methods: We simultaneously collected CSDH fluid and peripheral blood from 20 CSDH patients at the time of surgery. Biopsies of the dura mater and the CSDH capsule were obtained and analyzed by immunohistochemistry for C5b-C9 or C5a deposition. Biomarkers of inflammation and complement activation were analyzed by a 21-multiplex assay, including Adiponectin, Clusterin, Complement factor C9 and CRP. Complement factor C5a was analyzed separately by a commercial R-plex electrochemiluminescence assay. Results: Ten biomarkers differed significantly between peripheral blood and paired CSDH of which two were significantly increased in CSDH fluid (Clusterin and Cystatin C). Eight of the significantly altered biomarkers were significantly decreased in CSDH fluid, including C5a, Complement 9 and Adiponectin. There was no immunoreactivity for C5a or the C5b-C9 membrane attack complex in the dura or CSDH membrane. Conclusions: In CSDH levels of the complement inhibitor Clusterin were increased, whereas levels of C5a and C9 were decreased. Membrane attack complex C5b-C9 was not detected in the membrane or dura surrounding the CSDH. Inhibition of complement could lead to reduced clearance of debris in the CSDH as well as secondary inflammatory reactions.</p>}},
  author       = {{Marklund, Niklas and Zolfaghari, Shaian and Westerberg, Gustaf and Ruscher, Karsten and Englund, Elisabet and Redebrandt, Henrietta Nittby}},
  issn         = {{0360-3997}},
  keywords     = {{Biomarker; Chronic Subdural Hematoma; Complement Factor}},
  language     = {{eng}},
  publisher    = {{Springer}},
  series       = {{Inflammation}},
  title        = {{Complement Inhibition in Chronic Subdural Hematoma Fluid}},
  url          = {{http://dx.doi.org/10.1007/s10753-024-02210-3}},
  doi          = {{10.1007/s10753-024-02210-3}},
  year         = {{2024}},
}