Abstract:
BACKGROUND AND PURPOSE:A ruptured intracranial aneurysm (IA) is the leading cause of a subarachnoid hemorrhage. This study seeks to define a specific gene whose mutation leads to disease. METHODS:More than 500 IA probands and 100 affected families were enrolled and clinically characterized. Whole exome sequencing was performed on a large family, revealing a segregating THSD1 (thrombospondin type 1 domain containing protein 1) mutation. THSD1 was sequenced in other probands and controls. Thsd1 loss-of-function studies in zebrafish and mice were used for in vivo analyses and functional studies performed using an in vitro endothelial cell model. RESULTS:A nonsense mutation in THSD1 was identified that segregated with the 9 affected (3 suffered subarachnoid hemorrhage and 6 had unruptured IA) and was absent in 13 unaffected family members (LOD score 4.69). Targeted THSD1 sequencing identified mutations in 8 of 507 unrelated IA probands, including 3 who had suffered subarachnoid hemorrhage (1.6% [95% confidence interval, 0.8%-3.1%]). These THSD1 mutations/rare variants were highly enriched in our IA patient cohort relative to 89 040 chromosomes in Exome Aggregation Consortium (ExAC) database (P<0.0001). In zebrafish and mice, Thsd1 loss-of-function caused cerebral bleeding (which localized to the subarachnoid space in mice) and increased mortality. Mechanistically, THSD1 loss impaired endothelial cell focal adhesion to the basement membrane. These adhesion defects could be rescued by expression of wild-type THSD1 but not THSD1 mutants identified in IA patients. CONCLUSIONS:This report identifies THSD1 mutations in familial and sporadic IA patients and shows that THSD1 loss results in cerebral bleeding in 2 animal models. This finding provides new insight into IA and subarachnoid hemorrhage pathogenesis and provides new understanding of THSD1 function, which includes endothelial cell to extracellular matrix adhesion.
journal_name
Strokejournal_title
Strokeauthors
Santiago-Sim T,Fang X,Hennessy ML,Nalbach SV,DePalma SR,Lee MS,Greenway SC,McDonough B,Hergenroeder GW,Patek KJ,Colosimo SM,Qualmann KJ,Hagan JP,Milewicz DM,MacRae CA,Dymecki SM,Seidman CE,Seidman JG,Kim DHdoi
10.1161/STROKEAHA.116.014161subject
Has Abstractpub_date
2016-12-01 00:00:00pages
3005-3013issue
12eissn
0039-2499issn
1524-4628pii
STROKEAHA.116.014161journal_volume
47pub_type
杂志文章相关文献
STROKE文献大全abstract:BACKGROUND AND PURPOSE:Transcranial Doppler ultrasonography (TCD) is the standard technique for monitoring emboli in the cerebral circulation. Embolic signals have been detected with the use of this technique in most patients undergoing coronary artery bypass surgery. We previously reported that the majority of emboli ...
journal_title:Stroke
pub_type: 杂志文章
doi:10.1161/01.str.27.1.87
更新日期:1996-01-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Sonothrombolysis is a new treatment approach in acute ischemic stroke. The results of a monocenter, randomized clinical study are presented. METHODS:Subjects with acute middle cerebral artery main stem occlusion were randomized into a target group receiving 1-hour transcranial continuous insonat...
journal_title:Stroke
pub_type: 杂志文章,随机对照试验
doi:10.1161/STROKEAHA.107.503870
更新日期:2008-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Body mass index has been associated with ischemic stroke in older populations, but its association with stroke in younger populations is not known. In light of the current obesity epidemic in the United States, the potential impact of obesity on stroke risk in young adults deserves attention. ME...
journal_title:Stroke
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1161/STROKEAHA.115.008940
更新日期:2015-06-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Although the cause of stroke among patients with patent foramen ovale (PFO) may be due to paradoxical cerebral embolism (PCE), this mechanism is often difficult to prove. The aim of our study was to evaluate the association between brain imaging findings suggestive of embolism and PFO among ische...
journal_title:Stroke
pub_type: 杂志文章
doi:10.1161/01.str.29.5.944
更新日期:1998-05-01 00:00:00
abstract::Patients with infarctions in the territory of the right middle cerebral artery (RMCA) sometimes present with an agitated confusional state. We reviewed clinical data on 46 patients with RMCA infarcts and compared neurologic findings in patients with and without agitated confusion. Neither of the two patients presentin...
journal_title:Stroke
pub_type: 杂志文章
doi:10.1161/01.str.15.5.883
更新日期:1984-09-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Transient ischemic attacks (TIA) are not well described in children. We assessed the prevalence of risk factors for TIA requiring hospitalization in children in a large national database. METHODS:Using the Healthcare Cost and Utilization Project Kids' Inpatient Database, children aged 1 to 18 ye...
journal_title:Stroke
pub_type: 杂志文章
doi:10.1161/STROKEAHA.113.004526
更新日期:2014-03-01 00:00:00
abstract:BACKGROUND AND PURPOSE:If it could be determined whether cerebral blood flow can be maintained (autoregulated) during transient falls in arterial blood pressure, we might be able to identify patients with carotid stenosis who are at risk of stroke. However, conventional methods of determining autoregulation in such pat...
journal_title:Stroke
pub_type: 杂志文章
doi:10.1161/01.str.28.7.1340
更新日期:1997-07-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Emergency medical services routing of patients with acute stroke to designated centers may increase the proportion of patients receiving care at facilities meeting national standards and augment recruitment for prehospital stroke research. METHODS:We analyzed consecutive patients enrolled within...
journal_title:Stroke
pub_type: 杂志文章
doi:10.1161/STROKEAHA.115.010264
更新日期:2015-10-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Although a lower serum homocysteine concentration is associated with a reduced risk of stroke in epidemiologic studies, randomized, controlled trials have yielded mixed findings regarding the effect of therapeutic homocysteine lowering on stroke prevention. We performed a meta-analysis of randomi...
journal_title:Stroke
pub_type: 杂志文章,meta分析
doi:10.1161/STROKEAHA.109.573410
更新日期:2010-06-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Systemic administration of Toll-like receptor (TLR) 4 and TLR9 agonists before cerebral ischemia have been shown to reduce ischemic injury by reprogramming the response of the brain to stroke. Our goal was to explore the mechanism of TLR-induced neuroprotection by determining whether a TLR7 agoni...
journal_title:Stroke
pub_type: 杂志文章
doi:10.1161/STROKEAHA.111.641522
更新日期:2012-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:MRI characterization of carotid plaque has been studied recently as a potential tool to predict stroke caused by carotid atherosclerosis. We performed a systematic review and meta-analysis to summarize the association of MRI-determined intraplaque hemorrhage, lipid-rich necrotic core, and thinnin...
journal_title:Stroke
pub_type: 杂志文章,meta分析,评审
doi:10.1161/STROKEAHA.113.002551
更新日期:2013-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:We aimed to determine if ischemia involving Broca area predicts Broca aphasia more reliably in acute or chronic stroke. METHODS:We included consecutive right-hand-dominant patients with left hemisphere ischemic stroke (<48 hours from onset for acute stroke or >6 months after stroke for chronic s...
journal_title:Stroke
pub_type: 杂志文章
doi:10.1161/STROKEAHA.109.570374
更新日期:2010-02-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The effect of flow diverter (FD) on hemodynamic changes observed in aneurysms is inevitably affected by the actual structural configuration of deployed FD. We studied the resultant hemodynamic changes after implantation of FDs using computational fluid dynamic simulations based on micro-computed ...
journal_title:Stroke
pub_type: 杂志文章
doi:10.1161/STROKEAHA.113.001202
更新日期:2013-07-01 00:00:00
abstract::In patients with subarachnoid hemorrhage, particularly hemorrhage due to aneurysmal rupture, there was a positive significant relation between angiographic vessel constriction and vessel pathology (angiopathy). Furthermore, there was a positive relationship between post-hemorrhage survival time and the severity of ang...
journal_title:Stroke
pub_type: 杂志文章
doi:10.1161/01.str.14.2.240
更新日期:1983-03-01 00:00:00
abstract::We investigated the effects of phenytoin on the rate of enzymatic release of free fatty acids and on the levels of energy metabolites and nucleoside phosphates in ischemic brain. Phenytoin (10 mg/kg i.v.) was administered 30 minutes before the onset of ischemia induced in 30 male Wistar rats by occluding the basilar a...
journal_title:Stroke
pub_type: 杂志文章
doi:10.1161/01.str.21.9.1326
更新日期:1990-09-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Anemia is 1 potential mechanism by which the brain receives inadequate oxygenation. The purpose of this study was to determine in acute stroke patients whether lower hemoglobin values were associated with worse hemispatial neglect. METHODS:In 203 subjects, neglect testing batteries were administ...
journal_title:Stroke
pub_type: 杂志文章
doi:10.1161/STROKEAHA.110.585265
更新日期:2010-08-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Brain iron overload plays a detrimental role in brain injury after intracerebral hemorrhage (ICH). A recent study found that minocycline acts as an iron chelator and reduces iron-induced neuronal death in vitro. The present study investigated if minocycline reduces iron overload after ICH and iro...
journal_title:Stroke
pub_type: 杂志文章
doi:10.1161/STROKEAHA.111.623926
更新日期:2011-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The relationship between arterial recanalization, infarct size, and outcome in patients treated with intravenous thrombolytics remains unclear. Therefore, we aimed to determine the time course of recombinant tissue plasminogen activator (rtPA)-induced recanalization in patients with cardioembolic...
journal_title:Stroke
pub_type: 临床试验,杂志文章
doi:10.1161/hs1201.99821
更新日期:2001-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Chronic kidney disease may increase the risk for ischemic stroke or systemic embolism in patients with nonvalular atrial fibrillation (AF). We conducted a meta-analysis to summarize all published studies to investigate the link between chronic kidney disease and risk of thromboembolic events in A...
journal_title:Stroke
pub_type: 杂志文章,meta分析
doi:10.1161/STROKEAHA.114.006881
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The aim of this study was to determine the 30-day mortality and morbidity of intracerebral hemorrhage in a large metropolitan population and to determine the most important predictors of 30-day outcome. METHODS:We reviewed the medical records and computed tomographic films for all cases of spont...
journal_title:Stroke
pub_type: 杂志文章
doi:10.1161/01.str.24.7.987
更新日期:1993-07-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Stroke is a major healthcare problem in both the United States (US) and the United Kingdom (UK). Little comparative data are available concerning how generalist physicians in the two countries approach the management of patients at high risk of stroke. METHODS:Contemporaneous surveys of random s...
journal_title:Stroke
pub_type: 杂志文章
doi:10.1161/01.str.28.4.746
更新日期:1997-04-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Lower birth weight is associated with increased risk of stroke, but little is known about the mechanism for this association or influence in addition to vascular risk factors. We investigated whether there was an association between birth parameters and imaging markers of white matter integrity i...
journal_title:Stroke
pub_type: 杂志文章
doi:10.1161/STROKEAHA.108.527259
更新日期:2009-04-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Transcranial color-coded sonography is a new development in noninvasive cerebral vascular imaging. Reference data using this technique are described. METHODS:Blood velocities and pulsatility and resistance indices were determined in the anterior cerebral, middle cerebral, posterior cerebral, ver...
journal_title:Stroke
pub_type: 杂志文章
doi:10.1161/01.str.25.2.390
更新日期:1994-02-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The perfusion territories of the brain-feeding arteries are difficult to assess in vivo and therefore standard cerebral perfusion territory templates are often used to determine the relation between cerebral infarcts and the feeding vasculature. In the present study, we compared this infarct clas...
journal_title:Stroke
pub_type: 杂志文章
doi:10.1161/STROKEAHA.108.539866
更新日期:2009-05-01 00:00:00
abstract::Cerebral blood flow and clinical parameters were studied in 30 stroke patients at 15th, 30th, 60th, 90th days after the cerebral insult (Xenon 133 inhalation method). The clinical improvement was not accompanied by a progressive normalization of the CBF at rest. No relationship was found between the clinical data and ...
journal_title:Stroke
pub_type: 杂志文章
doi:10.1161/01.str.14.1.77
更新日期:1983-01-01 00:00:00
abstract:BACKGROUND AND PURPOSE:We examined the relationship of carotid artery lesions (CALs), with and without acoustic shadowing (AS), to incident ischemic stroke events in the Atherosclerosis Risk in Communities study cohort. METHODS:The study population consisted of 13 123 men and women aged 45 to 64 years, and free of str...
journal_title:Stroke
pub_type: 杂志文章
doi:10.1161/01.str.32.5.1120
更新日期:2001-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Spontaneous dissection of the cervical internal carotid artery (sICAD) is mainly assessed with MRI and magnetic resonance angiography (MRA), which are not always at hand. In contrast, color duplex sonography (CDS) is readily available. We undertook this prospective study to examine the accuracy o...
journal_title:Stroke
pub_type: 杂志文章
doi:10.1161/01.STR.0000198811.65068.16
更新日期:2006-02-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The Pediatric National Institutes of Health Stroke Scale (PedNIHSS), an adaptation of the adult National Institutes of Health Stroke Scale, is a quantitative measure of stroke severity shown to be reliable when scored prospectively. The ability to calculate the PedNIHSS score retrospectively woul...
journal_title:Stroke
pub_type: 杂志文章,多中心研究
doi:10.1161/STROKEAHA.111.633305
更新日期:2012-02-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The reliability of the National Institutes of Health Stroke Scale (NIHSS) has been established through testing its use in live and videotaped patients. This reliability testing has primarily focused on the use of the scale by neurologists. We sought to determine the reliability of the NIHSS as us...
journal_title:Stroke
pub_type: 杂志文章
doi:10.1161/01.str.28.2.307
更新日期:1997-02-01 00:00:00
abstract:BACKGROUND AND PURPOSE:To assess the role of the endothelial nitric oxide synthase (eNOS) gene variants as risk factors for early atherosclerosis, we sought to investigate whether two polymorphisms located in the exon 7 (Glu298-->Asp) and in the promoter region (T-786-->C) of the eNOS gene were associated with function...
journal_title:Stroke
pub_type: 杂志文章
doi:10.1161/01.STR.0000126482.86708.37
更新日期:2004-06-01 00:00:00