Complement C5 Contributes to Brain Injury After Subarachnoid Hemorrhage.

Abstract:

:Previous 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.

journal_name

Transl Stroke Res

authors

van Dijk BJ,Meijers JCM,Kloek AT,Knaup VL,Rinkel GJE,Morgan BP,van der Kamp MJ,Osuka K,Aronica E,Ruigrok YM,van de Beek D,Brouwer M,Pekna M,Hol EM,Vergouwen MDI

doi

10.1007/s12975-019-00757-0

subject

Has Abstract

pub_date

2020-08-01 00:00:00

pages

678-688

issue

4

eissn

1868-4483

issn

1868-601X

pii

10.1007/s12975-019-00757-0

journal_volume

11

pub_type

杂志文章
  • A Brain-Targeted Orally Available ROCK2 Inhibitor Benefits Mild and Aggressive Cavernous Angioma Disease.

    abstract::Cavernous angioma (CA) is a vascular pathology caused by loss of function in one of the 3 CA genes (CCM1, CCM2, and CCM3) that result in rho kinase (ROCK) activation. We investigated a novel ROCK2 selective inhibitor for the ability to reduce brain lesion formation, growth, and maturation. We used genetic methods to e...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-019-00725-8

    authors: McKerracher L,Shenkar R,Abbinanti M,Cao Y,Peiper A,Liao JK,Lightle R,Moore T,Hobson N,Gallione C,Ruschel J,Koskimäki J,Girard R,Rosen K,Marchuk DA,Awad IA

    更新日期:2020-06-01 00:00:00

  • Human Ischaemic Cascade Studies Using SH-SY5Y Cells: a Systematic Review and Meta-Analysis.

    abstract::Low translational yield for stroke may reflect the focus of discovery science on rodents rather than humans. Just how little is known about human neuronal ischaemic responses is confirmed by systematic review and meta-analysis revealing that data for the most commonly used SH-SY5Y human cells comprises only 84 papers....

    journal_title:Translational stroke research

    pub_type: 杂志文章,meta分析,评审

    doi:10.1007/s12975-018-0620-4

    authors: Liu Y,Eaton ED,Wills TE,McCann SK,Antonic A,Howells DW

    更新日期:2018-12-01 00:00:00

  • CCL11 (Eotaxin-1) Levels Predict Long-Term Functional Outcomes in Patients Following Ischemic Stroke.

    abstract::Circulating levels of the pro-inflammatory cytokine C-C motif chemokine 11 (CCL11, also known as eotaxin-1) are increased in several animal models of neuroinflammation, including traumatic brain injury and Alzheimer's disease. Increased levels of CCL11 have also been linked to decreased neurogenesis in mice. We hypoth...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-017-0545-3

    authors: Roy-O'Reilly M,Ritzel RM,Conway SE,Staff I,Fortunato G,McCullough LD

    更新日期:2017-12-01 00:00:00

  • P2X7 receptor inhibition increases CNTF in the subventricular zone, but not neurogenesis or neuroprotection after stroke in adult mice.

    abstract::Increasing endogenous ciliary neurotrophic factor (CNTF) expression with a pharmacological agent might be beneficial after stroke as CNTF both promotes neurogenesis and, separately, is neuroprotective. P2X7 purinergic receptor inhibition is neuroprotective in rats and increases CNTF release in rat CMT1A Schwann cells....

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-013-0265-2

    authors: Kang SS,Keasey MP,Hagg T

    更新日期:2013-10-01 00:00:00

  • Acute Multi-modal Neuroimaging in a Porcine Model of Endothelin-1-Induced Cerebral Ischemia: Defining the Acute Infarct Core.

    abstract::In a porcine ischemic stroke model, we sought to compare the acute predicted infarct core volume (PIV) defined by CT perfusion (CTP)-hemodynamic parameters and MR-diffusion-weighted imaging (MR-DWI)/apparent diffusion coefficient (ADC), with the true infarct core volume (TIV) as defined by histology. Ten Duroc-cross p...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-015-0394-x

    authors: d'Esterre CD,Aviv RI,Morrison L,Fainardi E,Lee TY

    更新日期:2015-06-01 00:00:00

  • Large Vessel Vasospasm Is Not Associated with Cerebral Cortical Hypoperfusion in a Murine Model of Subarachnoid Hemorrhage.

    abstract::Clinical studies on subarachnoid hemorrhage (SAH) have shown discrepancies between large vessel vasospasm, cerebral perfusion, and clinical outcome. We set out to analyze the contribution of large vessel vasospasm to impaired cerebral perfusion and neurological impairment in a murine model of SAH. SAH was induced in C...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-018-0647-6

    authors: Neulen A,Meyer S,Kramer A,Pantel T,Kosterhon M,Kunzelmann S,Goetz H,Thal SC

    更新日期:2018-07-12 00:00:00

  • Subarachnoid hemorrhage: a review of experimental studies on the microcirculation and the neurovascular unit.

    abstract::Increasingly, experimental research in subarachnoid hemorrhage (SAH) has investigated early brain injury and the microcirculation. A number of pathophysiological changes occur in the cerebral microvessels after SAH including altered vasoreactivity, vasoconstriction, inflammation, blood-brain barrier impairment, increa...

    journal_title:Translational stroke research

    pub_type: 杂志文章,评审

    doi:10.1007/s12975-014-0323-4

    authors: Tso MK,Macdonald RL

    更新日期:2014-04-01 00:00:00

  • Beneficial Effects of Delayed P7C3-A20 Treatment After Transient MCAO in Rats.

    abstract::Despite ischemic stroke being the fifth leading cause of death in the USA, there are few therapeutic options available. We recently showed that the neuroprotective compound P7C3-A20 reduced brain atrophy, increased neurogenesis, and improved functional recovery when treatment was initiated immediately post-reperfusion...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-017-0565-z

    authors: Loris ZB,Hynton JR,Pieper AA,Dietrich WD

    更新日期:2018-04-01 00:00:00

  • Role of Exosomes as a Treatment and Potential Biomarker for Stroke.

    abstract::Approximately, 16 million strokes occur worldwide each year, causing 6 million deaths and considerable disability, implying an enormous social, individual health, and economic burden. Due to this high incidence, strategies to promote stroke recovery are urgently needed. Research into new therapeutic approaches for str...

    journal_title:Translational stroke research

    pub_type: 杂志文章,评审

    doi:10.1007/s12975-018-0654-7

    authors: Otero-Ortega L,Laso-García F,Gómez-de Frutos M,Fuentes B,Diekhorst L,Díez-Tejedor E,Gutiérrez-Fernández M

    更新日期:2019-06-01 00:00:00

  • Inflammation of the choroid plexus and ependymal layer of the ventricle following intraventricular hemorrhage.

    abstract::Intraventricular hemorrhage (IVH), which afflicts thousands of people of all ages every year, frequently results in the development of communicating hydrocephalus. Classically, IVH-induced hydrocephalus has been attributed to reduced resorption of cerebrospinal fluid (CSF) due to dysfunction of arachnoid granulations,...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-011-0070-8

    authors: Simard PF,Tosun C,Melnichenko L,Ivanova S,Gerzanich V,Simard JM

    更新日期:2011-06-01 00:00:00

  • Intracerebral hemorrhage: clinical overview and pathophysiologic concepts.

    abstract::Intracerebral hemorrhage is by far the most destructive form of stroke. Apart from the management in a specialized stroke or neurological intensive care unit (NICU), no specific therapies have been shown to consistently improve outcomes after ICH. Current guidelines endorse early aggressive optimization of physiologic...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-012-0175-8

    authors: Rincon F,Mayer SA

    更新日期:2012-07-01 00:00:00

  • Magnesium sulfate treatment improves outcome in patients with subarachnoid hemorrhage: a meta-analysis study.

    abstract:OBJECTIVE:To elucidate the role of magnesium sulfate in patients with subarachnoid hemorrhagic (SAH) brain injury METHOD:Studies for the meta-analysis were identified from PubMed (1966 to 2009), Embase (1980 to 2009), and two Chinese journals (1989 to 2009). Paper selection was based on randomized controlled trials co...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-010-0022-8

    authors: Huang B,Khatibi NH,Tong L,Yan P,Xie P,Zhang JH

    更新日期:2010-06-01 00:00:00

  • Vasoconstriction and Impairment of Neurovascular Coupling after Subarachnoid Hemorrhage: a Descriptive Analysis of Retinal Changes.

    abstract::Impaired cerebral autoregulation and neurovascular coupling (NVC) contribute to delayed cerebral ischemia after subarachnoid hemorrhage (SAH). Retinal vessel analysis (RVA) allows non-invasive assessment of vessel dimension and NVC hereby demonstrating a predictive value in the context of various neurovascular disease...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-017-0585-8

    authors: Conzen C,Albanna W,Weiss M,Kürten D,Vilser W,Kotliar K,Zäske C,Clusmann H,Schubert GA

    更新日期:2018-06-01 00:00:00

  • Validity of bone marrow stromal cell expansion by animal serum-free medium for cell transplantation therapy of cerebral infarct in rats-a serial MRI study.

    abstract::This study was aimed to test the hypothesis that human bone marrow stromal cells (hBMSC) expanded in fetal calf serum (FCS)-free, platelet lysate (PL)-containing medium would retain their capacity of migration, survival, and neural differentiation when transplanted into the infarct brain, using serial in vivo magnetic...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-011-0098-9

    authors: Ito M,Kuroda S,Sugiyama T,Shichinohe H,Takeda Y,Nishio M,Koike T,Houkin K

    更新日期:2011-09-01 00:00:00

  • Activation of Sigma-1 Receptor Enhanced Pericyte Survival via the Interplay Between Apoptosis and Autophagy: Implications for Blood-Brain Barrier Integrity in Stroke.

    abstract::Stroke is a cerebrovascular disorder that affects many people worldwide. Pericytes play an important role in stroke progression and recovery. The sigma-1 receptor (σ-1R) signaling pathway has been suggested as having promising neuroprotective potential in treating stroke; however, whether σ-1R activation regulates per...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-019-00711-0

    authors: Zhang Y,Zhang X,Wei Q,Leng S,Li C,Han B,Bai Y,Zhang H,Yao H

    更新日期:2020-04-01 00:00:00

  • Correction to: Safety of Early Administration of Apixaban on Clinical Outcomes in Patients with Acute Large Vessel Occlusion.

    abstract::There was an error in Fig. 2d. The correct Fig. 2d is shown below. ...

    journal_title:Translational stroke research

    pub_type: 已发布勘误

    doi:10.1007/s12975-020-00871-4

    authors: Yoshimura S,Uchida K,Sakai N,Imamura H,Yamagami H,Tanaka K,Ezura M,Nonaka T,Matsumoto Y,Shibata M,Ohta H,Morimoto M,Fukawa N,Hatano T,Enomoto Y,Takeuchi M,Ota T,Shimizu F,Kimura N,Kamiya Y,Shimamura N,Morimoto T

    更新日期:2020-10-22 00:00:00

  • Sport-related concussion: "how many is too many?".

    abstract::The long-term effects of multiple sport-related concussions are currently at the center of debate in the popular press and scientific community. The question, "How many concussions are too many," is frequently asked in the competitive sport environment by parents, athletes, and coaches. While research suggests that a ...

    journal_title:Translational stroke research

    pub_type: 杂志文章,评审

    doi:10.1007/s12975-012-0237-y

    authors: Elbin RJ,Covassin T,Henry L,Whalen DJ,Wedge J,Kontos AP

    更新日期:2013-08-01 00:00:00

  • Polymorphonuclear neutrophil in brain parenchyma after experimental intracerebral hemorrhage.

    abstract::Polymorphonuclear neutrophils (PMNs) infiltration into brain parenchyma after cerebrovascular accidents is viewed as a key component of secondary brain injury. Interestingly, a recent study of ischemic stroke suggests that after ischemic stroke, PMNs do not enter brain parenchyma and as such may cause no harm to the b...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-014-0341-2

    authors: Zhao X,Sun G,Zhang H,Ting SM,Song S,Gonzales N,Aronowski J

    更新日期:2014-10-01 00:00:00

  • Infections Up to 76 Days After Stroke Increase Disability and Death.

    abstract::Early infection after stroke is associated with a poor outcome. We aimed to determine whether delayed infections (up to 76 days post-stroke) are associated with poor outcome at 90 days. Data came from the international Efficacy of Nitric Oxide Stroke (ENOS, ISRCTN99414122) trial. Post hoc data on infections were obtai...

    journal_title:Translational stroke research

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1007/s12975-017-0553-3

    authors: Learoyd AE,Woodhouse L,Shaw L,Sprigg N,Bereczki D,Berge E,Caso V,Christensen H,Collins R,Czlonkowska A,El Etribi A,Farr TD,Gommans J,Laska AC,Ntaios G,Ozturk S,Pocock SJ,Prasad K,Wardlaw JM,Fone KC,Bath PM,Truem

    更新日期:2017-12-01 00:00:00

  • A New Angiographic Collateral Grading System for Acute Basilar Artery Occlusion Treated with Endovascular Therapy.

    abstract::Poor clinical outcomes despite endovascular therapy (EVT) are common in patients with acute basilar artery occlusion (BAO). We aimed to develop a new angiographic collateral grading system for predicting 90-day functional outcomes of acute BAO after EVT. A prospectively registered consecutive cohort of acute BAO patie...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-020-00856-3

    authors: Gao F,Tong X,Sun X,Miao Z

    更新日期:2020-09-28 00:00:00

  • A brief history of behavioral assessment following experimental traumatic brain injury in juveniles.

    abstract::This review focuses on assessment of behavioral outcomes following traumatic brain injury in juvenile animal models. In the 15 years since the first publication in this field, the majority of studies have used rats roughly equivalent to human toddlers in terms of brain development. Few studies have tested ages closer ...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-011-0132-y

    authors: Hartman RE

    更新日期:2011-12-01 00:00:00

  • Treatment with the iron chelator, deferoxamine mesylate, alters serum markers of oxidative stress in stroke patients.

    abstract::The iron chelator, deferoxamine mesylate (DFO), has shown neuroprotective effects, mediated via suppression of iron-induced hydroxyl radical formation, in various animal models of ischemic and hemorrhagic stroke. Therefore, the objective of this study was to investigate whether DFO can exert similar actions in stroke ...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-009-0001-0

    authors: Selim M

    更新日期:2010-03-01 00:00:00

  • Tissue plasminogen activator induced delayed edema in experimental porcine intracranial hemorrhage: reduction with plasminogen activator inhibitor-1 administration.

    abstract::Hematoma puncture and subsequent clot lysis with recombinant tissue plasminogen activator (rtPA) emerged as an alternative therapy for spontaneous intracerebral hemorrhage (ICH) and is associated with delayed edema possibly counteracting the beneficial effects of hematoma volume reduction. We hypothesized that immedia...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-012-0188-3

    authors: Keric N,Maier GS,Samadani U,Kallenberg K,Dechent P,Brueck W,Heuer J,Rohde V

    更新日期:2012-07-01 00:00:00

  • Epigenetics and the environment: in search of the "toleroasome" vital to execution of ischemic preconditioning.

    abstract::Activation and repression of gene expression are key features of ischemic tolerance. Converging lines of inquiry from several groups suggests that epigenetic proteins may transduce sublethal stresses, including bioenergetic or oxidative stress into durable (2-3 days) changes in gene expression that mediate ischemic to...

    journal_title:Translational stroke research

    pub_type: 杂志文章,评审

    doi:10.1007/s12975-012-0235-0

    authors: Brand D,Ratan RR

    更新日期:2013-02-01 00:00:00

  • Proposed Definition of Experimental Secondary Ischemia for Mouse Subarachnoid Hemorrhage.

    abstract::Inconsistency in outcome parameters for delayed cerebral ischemia (DCI) makes it difficult to compare results between mouse studies, in the same way inconsistency in outcome parameters in human studies has for long obstructed adequate comparison. The absence of an established definition may in part be responsible for ...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-020-00796-y

    authors: van Lieshout JH,Marbacher S,Muhammad S,Boogaarts HD,Bartels RHMA,Dibué M,Steiger HJ,Hänggi D,Kamp MA

    更新日期:2020-10-01 00:00:00

  • Intra-operative Video Characterization of Carotid Artery Pulsation Patterns in Case Series with Post-endarterectomy Hypertension and Hyperperfusion Syndrome.

    abstract::Cerebral hyperperfusion syndrome (CHS) is a complication that can occur after carotid endarterectomy (CEA), the treatment of choice to decrease the subsequent risk of fatal or disabling stroke for patients with symptomatic severe stenosis of the carotid artery. Because of its rarity and complexity, the mechanism of th...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-017-0605-8

    authors: Xiao Y,Rivaz H,Kasuya H,Yokosako S,Mindru C,Teitelbaum J,Sirhan D,Sinclair D,Angle M,Lo BWY

    更新日期:2018-10-01 00:00:00

  • Neuroimaging of stroke and ischemia in animal models.

    abstract::Magnetic resonance imaging (MRI) has dramatically changed our ability to diagnose and treat stroke as well as follow its evolution and response to treatment. Early stroke and ischemia can be visualized using diffusion-weighted imaging that utilizes water diffusion within tissues as a reporter for evolving neuropatholo...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-011-0139-4

    authors: Obenaus A,Ashwal S

    更新日期:2012-03-01 00:00:00

  • Chronic Systemic Immune Dysfunction in African-Americans with Small Vessel-Type Ischemic Stroke.

    abstract::The incidence of small vessel-type (lacunar) ischemic strokes is greater in African-Americans compared to whites. The chronic inflammatory changes that result from lacunar stroke are poorly understood. To elucidate these changes, we measured serum inflammatory and thrombotic biomarkers in African-Americans at least 6 ...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-015-0424-8

    authors: Brown CM,Bushnell CD,Samsa GP,Goldstein LB,Colton CA

    更新日期:2015-12-01 00:00:00

  • The Pathophysiology of Intracerebral Hemorrhage Formation and Expansion.

    abstract::Intracerebral hemorrhage is a devastating disease. Despite its clinical importance, the pathophysiology of intracerebral hemorrhage is not well understood. Hematoma expansion occurs in a large subset of patients and is a predictor of poor outcomes. Since hematoma growth provides a potential opportunity for therapeutic...

    journal_title:Translational stroke research

    pub_type: 杂志文章,评审

    doi:10.1007/s12975-015-0410-1

    authors: Schlunk F,Greenberg SM

    更新日期:2015-08-01 00:00:00

  • Noninvasive Measurements of Cerebral Blood Flow, Oxygen Extraction Fraction, and Oxygen Metabolic Index in Human with Inhalation of Air and Carbogen using Magnetic Resonance Imaging.

    abstract::Noninvasive magnetic resonance (MR) methods have been explored to provide quantitative measurements of cerebral blood flow (CBF), oxygen extraction fraction (OEF), and oxygen metabolic index (OMI = CBF × OEF). In this study, we sought to evaluate whether MR measured OEF, CBF, and OMI can consistently detect the expect...

    journal_title:Translational stroke research

    pub_type: 杂志文章

    doi:10.1007/s12975-011-0142-9

    authors: An H,Sen S,Chen Y,Powers WJ,Lin W

    更新日期:2012-06-01 00:00:00