Effect of recombinant ADAMTS‐13 on microthrombosis and brain injury after experimental subarachnoid hemorrhage

Vergouwen, Mervyn D.I.; Knaup, Véronique L.; Roelofs, Joris J. T. H.; Boer, Onno J. de; Meijers, Joost C. M.

doi:10.1111/jth.12574

Cited by 28 publications

(31 citation statements)

References 26 publications

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“…In in vivo studies, ADAMTS‐13 was defined to play a protective role in ischemia‐reperfusion brain damage . In addition to this, in mice with subarachnoid hemorrhages, treatment with recombinant ADAMTS‐13 induces statistically significant reductions in the areas of microthrombi and damaged brain tissue . In addition to this information, in the experimental stroke models, ADAMTS‐13 deficiency was shown to exacerbate neuronal damage and addition of exogenous ADAMTS‐13 attenuates the condition and elevates the healing process .…”

Section: Discussionsupporting

confidence: 54%

Increased expressions of ADAMTS‐13 and apoptosis contribute to neuropathology during Toxoplasma gondii encephalitis in mice

Dinçel

Atmaca

2015

Neuropathology

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Toxoplasma gondii (T. gondii) is a protozoan parasite with the potential of causing severe encephalitis among immunocompromised humans and animals. Our previous study showed that T. gondii induces high nitric oxide (NO) production, high glial activation (GFAP) and neurofilament expressions, leading to severe neurodegeneration in toxoplasma encephalitis (TE) in the central nervous system (CNS). The aim of this experimental study was to investigate ADAMTS-13 expression and apoptosis in CNS and to identify whether they have any correlation with toxoplasmosis neuropathology and neurodegeneration. Mice were infected with ME49 strain T. gondii and the levels of ADAMTS-13, caspase 3, caspase 8, caspase 9, TNFR1 and Bcl-xL expressions were examined in brain tissues by immunohistochemistry, during the development and establishment of chronic infections at 10, 30 and 60 days post-infection. Results of the study revealed that the levels of ADAMTS-13 (P < 0.005), caspase 3 (P < 0.05), caspase 8 (P < 0.05), caspase 9 (P < 0.005) and TNFR1 (P < 0.05) expressions in the brain markedly increased while Bcl-xL expression decreased (P < 0.005). The most prominent finding from our study was that 10, 30 and 60 days post-infection ADAMTS-13 increased significantly and this may play an important role in the regulation and protection of the blood-brain barrier integrity and CNS microenvironment in TE. These results also suggest that T. gondii-mediated apoptosis might play a pivotal role and a different type of role in the mechanism of neurodegeneration and neuropathology in the process of TE. Furthermore, expression of ADAMTS-13 might give an idea of the progress and is critical for diagnosis of this disease. To the best of the authors' knowledge, this is the first report on ADAMTS-13 expression in the CNS of T. gondii-infected mice.

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Section: Discussionsupporting

confidence: 54%

Increased expressions of ADAMTS‐13 and apoptosis contribute to neuropathology during Toxoplasma gondii encephalitis in mice

Dinçel

Atmaca

2015

Neuropathology

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“…Two recent studies showed that recombinant ADAMTS13 reduces microthrombosis and brain injury after experimental SAH. [40][41] ADAMTS13 rapidly cleaves ultralarge vWF multimers, reduces platelet adhesion and aggregation, and downregulates inflammation and thrombus formation. [42][43][44][45] In stroke models, recombinant ADAMTS13 did not affect bleeding rates.…”

Section: Discussionmentioning

confidence: 99%

Hemostasis and Fibrinolysis in Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage: A Systematic Review

Boluijt

Meijers

Rinkel

et al. 2015

J Cereb Blood Flow Metab

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Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) has been associated with microthrombosis, which can result from activated hemostasis, inhibited fibrinolysis, or both. We systematically searched the PUBMED and EMBASE databases to identify hemostatic or fibrinolytic parameters that can be used for the prediction or diagnosis of DCI, or that inform on the pathogenesis of DCI and may serve as treatment targets. We included 24 studies that fulfilled predefined criteria and described 39 biomarkers. Only one study fulfilled predefined criteria for high quality. Since no parameter on admission was associated with DCI and in none of the included studies blood was drawn at the time of clinical deterioration, none of the studied parameters can presently be used for the prediction or diagnosis of DCI. Regarding the pathogenesis of DCI, it was shown that compared with patients without DCI those with DCI had higher levels of von Willebrand factor and platelet activating factor in plasma 5 to 9 days after aSAH, membrane tissue factor in cerebrospinal fluid 5 to 9 days after aSAH, and D-dimer in plasma 11 to 14 days after aSAH. Confirmation in high-quality studies is needed to investigate whether these parameters can serve as targets for new intervention studies.

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“…Although only a few studies have been performed evaluating ADAMTS13 levels in patients with ischemic stroke, a meta-analysis of 616 patients demonstrated a clear association between reduced ADAMTS13 levels and increased risk of stroke [OR 2.72; 95% CI (1.52 – 4.86)] (2). Experimental murine models of SAH demonstrate that Adamts13 −/− mice sustain larger areas of microvascular thrombosis than do wild-type mice, but that with recombinant ADAMTS13 treatment, the knock out mice can experience smaller thrombosis areas, similar to wild type mice (45). Therefore, recombinant ADAMTS13 may be a putative treatment option in SAH patients at risk for DCI.…”

Section: Discussionmentioning

confidence: 99%

Plasma ADAMTS13 activity and von Willebrand factor antigen and activity in patients with subarachnoid haemorrhage

Kumar¹,

Cao²,

McDaniel³

et al. 2017

Thromb Haemost

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Summary Background Increased von Willebrand factor (VWF) and reduced ADAMTS13 activity are associated with arterial thrombosis. This may also be the culprit mechanism implicated in delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage (SAH). Objective To determine plasma VWF and ADAMTS13 in patients with SAH and healthy subjects; and to explore the levels of those markers and outcome after SAH. Methods 40 consecutive patients were enrolled between September 2007 and April 2014 in a pilot study. Plasma samples were collected from SAH patients on post-bleed day (PBD) 0, 1, 3, 5, 7 and 10 and healthy controls. VWF antigen (VWFAg) and VWF activity (VWFAc) were determined by enzyme-linked immunoassay and collagen binding assay, respectively. ADAMTS13 activity was determined by the cleavage of a fluorescent substrate. Univariate descriptive statistics and cluster analyses were performed based on outcomes in the group with SAH only. Results Mean age of SAH patients was 52.4 years (26–84 years) and 30 (75%) were women. 12/40 (30%) had a high Hunt and Hess grade (IV–V) and 25 (62.5%) were treated with coil embolization. Plasma VWFAg and VWFAc were significantly higher in SAH patients than those in healthy subjects on each PBD (p<0.0001). Concurrently, plasma ADAMTS13 activity in SAH patients was significantly lower than that in healthy subjects (p<0.0001). Among those with SAH, cluster analysis demonstrated that patients with higher VWFAg and VWFAc and/or lower ADAMTS13 activity might be at risk of increased mortality. Conclusions The relative deficiency of plasma ADAMTS13 activity in SAH patients may associate with worse outcome.

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Effect of recombinant ADAMTS‐13 on microthrombosis and brain injury after experimental subarachnoid hemorrhage

Cited by 28 publications

References 26 publications

Increased expressions of ADAMTS‐13 and apoptosis contribute to neuropathology during Toxoplasma gondii encephalitis in mice

Increased expressions of ADAMTS‐13 and apoptosis contribute to neuropathology during Toxoplasma gondii encephalitis in mice

Hemostasis and Fibrinolysis in Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage: A Systematic Review

Plasma ADAMTS13 activity and von Willebrand factor antigen and activity in patients with subarachnoid haemorrhage

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