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van Dijk, Bart J.; Meijers, Joost C.M.; Kloek, Anne T.; Knaup, Veronique L.; Rinkel, Gabriel J.E.; Morgan, B. Paul; van der Kamp, Marije J.; Osuka, Koji; Aronica, Eleonora; Ruigrok, Ynte M.; van de Beek, Diederik; Brouwer, Matthijs; Pekna, Marcela; Hol, Elly M.; Vergouwen, Mervyn D.I.

Complement C5 Contributes to Brain Injury After Subarachnoid Hemorrhage

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  • Media type: E-Article
  • Title: Complement C5 Contributes to Brain Injury After Subarachnoid Hemorrhage
  • Contributor: van Dijk, Bart J.; Meijers, Joost C.M.; Kloek, Anne T.; Knaup, Veronique L.; Rinkel, Gabriel J.E.; Morgan, B. Paul; van der Kamp, Marije J.; Osuka, Koji; Aronica, Eleonora; Ruigrok, Ynte M.; van de Beek, Diederik; Brouwer, Matthijs; Pekna, Marcela; Hol, Elly M.; Vergouwen, Mervyn D.I.
  • Published: Springer Science and Business Media LLC, 2020
  • Published in: Translational Stroke Research, 11 (2020) 4, Seite 678-688
  • Language: English
  • DOI: 10.1007/s12975-019-00757-0
  • ISSN: 1868-4483; 1868-601X
  • Origination:
  • Footnote:
  • Description: AbstractPrevious studies showed that complement activation is associated with poor functional outcome after aneurysmal subarachnoid hemorrhage (SAH). We investigated whether complement activation is underlying brain injury after aneurysmal SAH (n = 7) and if it is an appropriate treatment target. We investigated complement expression in brain tissue of aneurysmal SAH patients (n = 930) and studied the role of common genetic variants in C3 and C5 genes in outcome. We analyzed plasma levels (n = 229) to identify the functionality of a single nucleotide polymorphism (SNP) associated with outcome. The time course of C5a levels was measured in plasma (n = 31) and CSF (n = 10). In an SAH mouse model, we studied the extent of microglia activation and cell death in wild-type mice, mice lacking the C5a receptor, and in mice treated with C5-specific antibodies (n = 15 per group). Brain sections from aneurysmal SAH patients showed increased presence of complement components C1q and C3/C3b/iC3B compared to controls. The complement component 5 (C5) SNP correlated with C5a plasma levels and poor disease outcome. Serial measurements in CSF revealed that C5a was > 1400-fold increased 1 day after aneurysmal SAH and then gradually decreased. C5a in plasma was 2-fold increased at days 3–10 after aneurysmal SAH. In the SAH mouse model, we observed a ≈ 40% reduction in both microglia activation and cell death in mice lacking the C5a receptor, and in mice treated with C5-specific antibodies. These data show that C5 contributes to brain injury after experimental SAH, and support further study of C5-specific antibodies as novel treatment option to reduce brain injury and improve prognosis after aneurysmal SAH.