Ficolin-3–mediated lectin complement pathway activation in patients with subarachnoid hemorrhage

Zanier, Elisa R.; Zangari, Rosalia; Munthe-Fog, Lea; Hein, Estrid; Zoerle, Tommaso; Conte, V.; Orsini, Franca; Tettamanti, Mauro; Stocchetti, Nino; Garred, Peter; Simoni, Maria Grazia De

doi:10.1212/wnl.0000000000000020

Cited by 32 publications

(40 citation statements)

References 40 publications

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“…Follow-up studies have extended these observations, documenting an increase in C3 and C3a plasma levels in patients with small vessel disease or cardioembolic stroke when compared to controls, and additionally demonstrating a positive correlation between their levels and unfavorable outcome in cardioembolic stroke (Stokowska et al, 2013). Acute (day 1–2) plasma sC5b-9 levels in patients with either ischemic or hemorrhagic stroke have been shown to be significantly increased when compared to non-stroke controls (Széplaki et al, 2009; Zanier et al, 2014) and shown to increase over time during post-stroke recovery (Pedersen et al, 2004). In a cohort of mild stroke patients, Mocco et al (2006b), observed decreased plasma sC5b-9 levels when compared to non-stroke controls.…”

Section: The Disruptive Overwhelming Power Of Complement In Acute Neumentioning

confidence: 99%

Versatility of the complement system in neuroinflammation, neurodegeneration and brain homeostasis

Orsini

Blasio

Zangari

et al. 2014

Front. Cell. Neurosci.

178

162

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The immune response after brain injury is highly complex and involves both local and systemic events at the cellular and molecular level. It is associated to a dramatic over-activation of enzyme systems, the expression of proinflammatory genes and the activation/recruitment of immune cells. The complement system represents a powerful component of the innate immunity and is highly involved in the inflammatory response. Complement components are synthesized predominantly by the liver and circulate in the bloodstream primed for activation. Moreover, brain cells can produce complement proteins and receptors. After acute brain injury, the rapid and uncontrolled activation of the complement leads to massive release of inflammatory anaphylatoxins, recruitment of cells to the injury site, phagocytosis and induction of blood brain barrier (BBB) damage. Brain endothelial cells are particularly susceptible to complement-mediated effects, since they are exposed to both circulating and locally synthesized complement proteins. Conversely, during neurodegenerative disorders, complement factors play distinct roles depending on the stage and degree of neuropathology. In addition to the deleterious role of the complement, increasing evidence suggest that it may also play a role in normal nervous system development (wiring the brain) and adulthood (either maintaining brain homeostasis or supporting regeneration after brain injury). This article represents a compendium of the current knowledge on the complement role in the brain, prompting a novel view that complement activation can result in either protective or detrimental effects in brain conditions that depend exquisitely on the nature, the timing and the degree of the stimuli that induce its activation. A deeper understanding of the acute, subacute and chronic consequences of complement activation is needed and may lead to new therapeutic strategies, including the ability of targeting selective step in the complement cascade.

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Section: The Disruptive Overwhelming Power Of Complement In Acute Neumentioning

confidence: 99%

Versatility of the complement system in neuroinflammation, neurodegeneration and brain homeostasis

Orsini

Blasio

Zangari

et al. 2014

Front. Cell. Neurosci.

178

162

View full text Add to dashboard Cite

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“…Complement activation has been demonstrated to be associated with some acute brain injury diseases including aSAH (2,3). In this study, functional MBL deficiency was defined as serum levels ≤100 ng/ml, as this cutoff has been shown to discriminate reasonably well between individuals with or without homozygosity for MBL variant alleles (34).…”

Section: Discussionmentioning

confidence: 99%

Serum mannose-binding lectin levels after aneurysmal subarachnoid hemorrhage

Cai

Sun

2016

Acta Neurol Scand

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“…[61][62][63][64] In SAH in particular, complement activation has been associated with poorer functional outcomes and even vasospasm. [60,[65][66][67] Dysregulation of any of the above processes, deficiencies in the complement proteins, and activation by various molecules can lead to a pathological over-or under-activation of the complement system. These complement disorders [ Table 1] include paroxysmal nocturnal hemoglobulinuria (PNH), hereditary angioedema, and atypical hemolytic uremic syndrome.…”

Section: Function Of the Complement Systemmentioning

confidence: 99%

“…Indeed, as mentioned, there is evidence that the complement system is upregulated in patients with SAH. [60,65,66] In response to this concern, Tulamo et al [84,100,101] have argued that the increased density of macrophage infiltration in ruptured versus unruptured aneurysms argues for a more chronic inflammatory process, as dense accumulation of macrophages typically occurs over days to weeks following an acute injury. In addition, they point out that although less concentrated, complement deposits were found in unruptured aneurysms.…”

Section: Role Of Complement In Aneurysmsmentioning

confidence: 99%

Role of the complement cascade in cerebral aneurysm formation, growth, and rupture

Taylor¹,

Appelboom²,

Zilinyi³

et al. 2015

Neuroimmunol Neuroinflammation

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A B S T R A C TRupture of intracranial aneurysms is the most common cause of nontraumatic subarachnoid hemorrhage, but the intricate neuroinflammatory processes which contribute to aneurysm pathophysiology are not well-understood. Mounting evidence has implicated the complement cascade in the progression of aneurysms from their formation to rupture. In this article, we identify and review studies that have sought to determine the role of the complement system in the aneurysm pathogenesis. The studies were generally conducted by immunhistological analyses on aneurysm tissue collected intraoperatively, and multiple components of the complement cascade and its modulators were identified in specific regions of the aneurysm wall. The results of the studies suggest that the complement cascade is locally upregulated and disinhibited in the perianeurysmal environment, and that it contributes to chronic as well as acute immunological damage to the aneurysm wall. In the future, understanding the mechanisms at work in complement-mediated damage is necessary to leading the development of novel therapies.

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Ficolin-3–mediated lectin complement pathway activation in patients with subarachnoid hemorrhage

Cited by 32 publications

References 40 publications

Versatility of the complement system in neuroinflammation, neurodegeneration and brain homeostasis

Versatility of the complement system in neuroinflammation, neurodegeneration and brain homeostasis

Serum mannose-binding lectin levels after aneurysmal subarachnoid hemorrhage

Role of the complement cascade in cerebral aneurysm formation, growth, and rupture

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