Deficiency of Factor VII activating protease alters the outcome of ischemic stroke in mice

Abstract Factor VII activating protease (FSAP) is a circulating protease with a putative role in hemostasis, remodeling and inflammation. A polymorphism giving rise to low proteolytic activity has been associated with an increased risk of stroke and carotid stenosis. To date, no in vivo studies or mechanistic information is available to explain these results. Based on the polymorphism data we hypothesize that a lack of endogenous FSAP will increase the severity of stroke. Stroke was induced by applying thrombin in the middle cerebral artery in wild‐type (WT) and FSAP−/− mice. Increased stroke volume and worsened neurological deficit were observed in FSAP−/− mice. Raised levels of FSAP protein were detected in the infarcted area of WT mice together with enhanced leukocyte infiltration and apoptosis in FSAP−/− mice. There was a concomitant increase in the activation of the NFκB pathway and decrease in expression of the PI3K/AKT pathway proteins. At a cellular level, FSAP increased cell survival and decreased apoptosis in primary cortical neurons and astrocytes exposed to tPA/NMDA excitotoxicity or oxygen glucose deprivation (OGD)/reoxygenation, respectively. This was mediated via the PI3K/AKT pathway with involvement of the protease activated receptor‐1. To corroborate the human epidemiological data, which link FSAP with stroke, we now show that the lack of FSAP in mice worsens the outcome of stroke. In the absence of FSAP there was...
Source: European Journal of Neuroscience - Category: Neuroscience Authors: Tags: Research Report Source Type: research

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Conclusions: Stroke education in China should focus on patients' poor understanding of the importance for sustained antihypertensive medication adherence to improve blood pressure control and prevent stroke.
Source: Journal of Cardiovascular Nursing - Category: Nursing Tags: Feature Article/Online Only Source Type: research
Abstract Nicotinamide adenine dinucleotide phosphate oxidase (NOX) is a multisubunit enzyme complex that utilizes nicotinamide adenine dinucleotide phosphate to produce superoxide anions and other reactive oxygen species. Under normal circumstances, reactive oxygen species mediate a number of important cellular functions, including the facilitation of adaptive immunity. In pathogenic circumstances, however, excess reactive oxygen species generated by NOX promotes apoptotic cell death. In ischemic stroke, in particular, it has been shown that both NOX activation and derangements in glucose metabolism result in incr...
Source: Cell Research - Category: Cytology Authors: Tags: Neural Regen Res Source Type: research
Publication date: Available online 14 February 2019Source: Journal of NeuroradiologyAuthor(s): Fabrizio Sallustio, Caterina Motta, Stefano Merolla, Giacomo Koch, Francesco Mori, Fana Alemseged, Daniele Morosetti, Valerio Ros Da, Roberto Gandini, Marina DiomediABSTRACTBackground and purpose: the effect of intravenous heparin during mechanical thrombectomy for acute ischemic stroke is not clear. We aimed to study efficacy and safety of heparin use during endovascular stroke treatment in a real-world setting.Materials and Methods: patients with anterior circulation stroke were divided, based on the use of intraprocedural hepa...
Source: Journal of Neuroradiology - Category: Radiology Source Type: research
Authors: Ercoli T, Dagostino S, Pierri V, Cannas A, Solla P, Uselli S, Scapin E, Saba L, Defazio G Abstract PMID: 30758162 [PubMed - as supplied by publisher]
Source: Journal of Sports Medicine and Physical Fitness - Category: Sports Medicine Tags: J Sports Med Phys Fitness Source Type: research
Publication date: Available online 14 February 2019Source: Biocybernetics and Biomedical EngineeringAuthor(s): G.B. Praveen, Anita Agrawal, Ponraj Sundaram, Sanjay SardesaiAbstractDetection of ischemic stroke lesions plays a vital role in the assessment of stroke treatments such as thrombolytic therapy and embolectomy. Manual detection and quantification of stroke lesions is a time-consuming and cumbersome process. In this paper, we present a novel automatic method to detect acute ischemic stroke lesions from Magnetic Resonance Image (MRI) volumes using textural and unsupervised learned features. The proposed method profic...
Source: Biocybernetics and Biomedical Engineering - Category: Biomedical Engineering Source Type: research
Publication date: Available online 10 February 2019Source: NeuroImageAuthor(s): Enfeng Wang, Yin Wu, Jerry S. Cheung, Takahiro Igarashi, Limin Wu, Xiaoan Zhang, Phillip Zhe SunAbstractpH-weighted amide proton transfer (APT) MRI is sensitive to tissue pH change during acute ischemia, complementing conventional perfusion and diffusion stroke imaging. However, the currently used pH-weighted magnetization transfer (MT) ratio asymmetry (MTRasym) analysis is of limited pH specificity. To overcome this, MT and relaxation normalized APT (MRAPT) analysis has been developed that to homogenizes the background signal, thus providing h...
Source: NeuroImage - Category: Neuroscience Source Type: research
This study aimed to determine the body mass index (BMI) of fatal stroke cases amongst young adults, their clinical characteristics and the association with BMI with risk factors. All cases aged 15-44 years where death was attributed to stroke for whom BMI was available were retrieved from the National Coronial Information System (1/1/2009-31/12/2016). 179 cases were identified: haemorrhagic (165), ischaemic (5), thrombotic (6), mycotic (3), embolic (0). Proportions in each BMI category were: underweight (5.6%), normal weight (37.4%), overweight (27.4%), obese (29.6%). There was a significant linear trend in the proportion ...
Source: Journal of Forensic and Legal Medicine - Category: Forensic Medicine Source Type: research
In conclusion, de-escalation of antiplatelet therapy is associated with nonsignificant differences in both ischemic events and major bleeding compared with standard potent antiplatelet therapy in patients undergoing percutaneous coronary intervention. The feasibility and even superiority of this strategy need to be elucidated by further randomized trials. PMID: 30759033 [PubMed - as supplied by publisher]
Source: Platelets - Category: Hematology Tags: Platelets Source Type: research
Conditions:   Stroke, Ischemic;   Healthy Intervention:   Other: stochastic resonance electrical stimulation Sponsors:   National Yang Ming University;   Taipei Veterans General Hospital, Taiwan Recruiting
Source: - Category: Research Source Type: clinical trials
Conclusions: Patients with RD and acute vertebrobasilar stroke should be thoroughly monitored to prevent ICH after thrombectomy. Our results support performing mechanical thrombectomy in acute stroke patients with large vessel occlusions of the posterior circulation, irrespective of their renal function.Cerebrovasc Dis 2019;47:48 –56
Source: Cerebrovascular Diseases - Category: Neurology Source Type: research
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