White matter lesions in an unselected cohort of the elderly: molecular pathology suggests origin from chronic hypoperfusion injury.


BACKGROUND AND PURPOSE:"Incidental" MRI white matter (WM) lesions, comprising periventricular lesions (PVLs) and deep subcortical lesions (DSCLs), are common in the aging brain. Direct evidence of ischemia associated with incidental WM lesions (WMLs) has been lacking, and their pathogenesis is unresolved. METHODS:A population-based, postmortem cohort (n=456) of donated brains was examined by MRI and pathology. In a subsample of the whole cohort, magnetic resonance images were used to sample and compare WMLs and nonlesional WM for molecular markers of hypoxic injury. RESULTS:PVL severity was associated with loss of ventricular ependyma (P=0.004). For DSCLs, there was arteriolar sclerosis compared with normal WM (vessel wall thickness and perivascular enlargement; both P<0.001). Capillary endothelial activation (ratio of intercellular adhesion molecule to basement membrane collagen IV; P<0.001) and microglial activation (CD68 expression; P=0.002) were elevated in WMLs. Immunoreactivity for hypoxia-inducible factors (HIFs) HIF1alpha and HIF2alpha was elevated in DSCLs (P=0.003 and P=0.005). Other hypoxia-regulated proteins were also increased in WMLs: matrix metalloproteinase-7 (PVLs P<0.001; DSCLs P=0.009) and the number of neuroglobin-positive cells (WMLs P=0.02) reaching statistical significance. The severity of congophilic amyloid angiopathy was associated with increased HIF1alpha expression in DSCLs (P=0.04). CONCLUSIONS:The data support a hypoxic environment within MRI WMLs. Persistent HIF expression may result from failure of normal adaptive mechanisms. WM ischemia appears to be a common feature of the aging brain.






Fernando MS,Simpson JE,Matthews F,Brayne C,Lewis CE,Barber R,Kalaria RN,Forster G,Esteves F,Wharton SB,Shaw PJ,O'Brien JT,Ince PG,MRC Cognitive Function and Ageing Neuropathology Study Group.




Has Abstract


2006-06-01 00:00:00
















  • Computed tomography in prognostic stroke evaluation.

    abstract:BACKGROUND AND PURPOSE:Computed tomography is now routinely used in many hospitals to investigate cerebrovascular disease. The purpose of our prospective study was to determine whether cranial computed tomography in connection with neurological assessment was useful in prognostic evaluation of survival after acute stro...


    pub_type: 杂志文章


    authors: Rasmussen D,Køhler O,Worm-Petersen S,Blegvad N,Jacobsen HL,Bergmann I,Egeblad M,Friis M,Nielsen NT

    更新日期:1992-04-01 00:00:00

  • The effect of a simulated subarachnoid hemorrhage on cerebral blood flow in the monkey.

    abstract::The hydrogen clearance method was used to measure local and total cerebral blood flow (CBF) in the rhesus monkey before and for five hours after a simulated subarachnoid hemorrhage (SAH). CBF remained stable after SAH unless SAH was associated with a fall in cerebral perfusion pressure. In addition, cerebrovascular re...


    pub_type: 杂志文章


    authors: Martins AN,Doyle TF,Newby N,Kobrine AI,Ramirez A

    更新日期:1975-11-01 00:00:00

  • Fluctuation of lipid peroxides and related enzyme activities at time of stroke in stroke-prone spontaneously hypertensive rats.

    abstract::The levels of lipid peroxides, determined as thiobarbituric acid reactive substances (TBARS), and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), were examined in the blood from stroke-prone spontaneously hypertensive rats (SHRSP), with and without cerebral lesions, and normotensive W...


    pub_type: 杂志文章


    authors: Tomita I,Sano M,Serizawa S,Ohta K,Katou M

    更新日期:1979-05-01 00:00:00

  • Effect of peer education on stroke prevention: the prevent recurrence of all inner-city strokes through education randomized controlled trial.

    abstract:BACKGROUND AND PURPOSE:Efforts to reduce disparities in recurrent stroke among Black and Latino stroke survivors have met with limited success. We aimed to determine the effect of peer education on secondary stroke prevention among predominantly minority stroke survivors. METHODS:Between 2009 and 2012, we enrolled 600...


    pub_type: 杂志文章,随机对照试验


    authors: Kronish IM,Goldfinger JZ,Negron R,Fei K,Tuhrim S,Arniella G,Horowitz CR

    更新日期:2014-11-01 00:00:00

  • Pressure-flow relations in canine collateral-dependent cerebrum.

    abstract:BACKGROUND AND PURPOSE:The pressure-flow relation has been characterized in normal cerebrum, but it has not been studied in cerebrum dependent on collateral flow. The purpose of this investigation was to examine the relation between systemic pressure, regional cerebral blood flow, and middle cerebral artery branch pres...


    pub_type: 杂志文章


    authors: Muhonen MG,Sawin PD,Loftus CM,Heistad DD

    更新日期:1992-07-01 00:00:00

  • Artery-to-artery embolism from a thrombus formed in stenotic middle cerebral artery. Report of an autopsy case.

    abstract::The authors report an autopsy case with repeated transient ischemic attacks and subsequent strokes demonstrating evidence of artery-to-artery embolism from thrombi generated in the stenotic middle cerebral artery to the distal cortical branches. This case substantiates the existence of intracranial artery-to-artery em...


    pub_type: 杂志文章


    authors: Masuda J,Ogata J,Yutani C,Miyashita T,Yamaguchi T

    更新日期:1987-05-01 00:00:00

  • Auditory discrimination after left-hemisphere stroke: a mismatch negativity follow-up study.

    abstract:BACKGROUND AND PURPOSE:We sought to determine the recovery of cortical auditory discrimination in aphasic, left-hemisphere-stroke patients by using an electrophysiological response called mismatch negativity (MMN) and speech-comprehension tests. METHODS:MMN in 8 left-hemisphere stroke patients was recorded in response...


    pub_type: 临床试验,杂志文章


    authors: Ilvonen TM,Kujala T,Kiesiläinen A,Salonen O,Kozou H,Pekkonen E,Roine RO,Kaste M,Näätänen R

    更新日期:2003-07-01 00:00:00

  • Craniotomy for treatment of unruptured aneurysms is not associated with long-term cognitive dysfunction.

    abstract:BACKGROUND AND PURPOSE:Many studies have reported frequent cognitive deficits associated with subarachnoid hemorrhage (SAH) and aneurysm repair. One study found more severe cognitive deficits after clipping than coiling of aneurysms, raising the possibility that deficits are due to surgery instead of SAH itself. This p...


    pub_type: 临床试验,杂志文章


    authors: Tuffiash E,Tamargo RJ,Hillis AE

    更新日期:2003-09-01 00:00:00

  • Blend Sign on Computed Tomography: Novel and Reliable Predictor for Early Hematoma Growth in Patients With Intracerebral Hemorrhage.

    abstract:BACKGROUND AND PURPOSE:Early hematoma growth is not uncommon in patients with intracerebral hemorrhage and is an independent predictor of poor functional outcome. The purpose of our study was to report and validate the use of our newly identified computed tomographic (CT) blend sign in predicting early hematoma growth....


    pub_type: 杂志文章


    authors: Li Q,Zhang G,Huang YJ,Dong MX,Lv FJ,Wei X,Chen JJ,Zhang LJ,Qin XY,Xie P

    更新日期:2015-08-01 00:00:00

  • Disparities in Antihypertensive Prescribing After Stroke: Linked Data From the Australian Stroke Clinical Registry.

    abstract::Background and Purpose- Despite evidence to support the prescription of antihypertensive medications before hospital discharge to promote medication adherence and prevent recurrent events, many patients with stroke miss out on these medications at discharge. We aimed to examine patient, clinical, and system-level diff...


    pub_type: 杂志文章


    authors: Dalli LL,Kim J,Thrift AG,Andrew NE,Lannin NA,Anderson CS,Grimley R,Katzenellenbogen JM,Boyd J,Lindley RI,Pollack M,Jude M,Durairaj R,Shah D,Cadilhac DA,Kilkenny MF

    更新日期:2019-12-01 00:00:00

  • Mesenchymal stem cell transplantation attenuates brain injury after neonatal stroke.

    abstract:BACKGROUND AND PURPOSE:Brain injury caused by stroke is a frequent cause of perinatal morbidity and mortality with limited therapeutic options. Mesenchymal stem cells (MSC) have been shown to improve outcome after neonatal hypoxic-ischemic brain injury mainly by secretion of growth factors stimulating repair processes....


    pub_type: 杂志文章


    authors: van Velthoven CT,Sheldon RA,Kavelaars A,Derugin N,Vexler ZS,Willemen HL,Maas M,Heijnen CJ,Ferriero DM

    更新日期:2013-05-01 00:00:00

  • Evaluation of cerebrovascular disease by combined extracranial and transcranial Doppler sonography. Experience in 1,039 patients.

    abstract::Results from 1,039 combined cervical and transcranial Doppler examinations are reported. Satisfactory transcranial signals were not found in 2.7% of the cases. Compared with angiography, the accuracy of transcranial criteria in assessing collateral flow over the circle of Willis was 94 and 88% for anterior and posteri...


    pub_type: 杂志文章


    authors: Grolimund P,Seiler RW,Aaslid R,Huber P,Zurbruegg H

    更新日期:1987-11-01 00:00:00

  • Admission fibrinolytic profile is associated with symptomatic hemorrhagic transformation in stroke patients treated with tissue plasminogen activator.

    abstract:BACKGROUND AND PURPOSE:Symptomatic intracranial hemorrhage (SICH) is the most feared complication after tissue plasminogen activator (tPA) stroke treatment. Endogenous fibrinolysis inhibitors play an essential role in the coagulation/fibrinolysis balance and may be involved in the bleeding process. We aim to determine ...


    pub_type: 杂志文章


    authors: Ribo M,Montaner J,Molina CA,Arenillas JF,Santamarina E,Quintana M,Alvarez-Sabín J

    更新日期:2004-09-01 00:00:00

  • Urgent carotid surgery and stenting may be safe after systemic thrombolysis for stroke.

    abstract:BACKGROUND AND PURPOSE:Early carotid surgery or stenting after thrombolytic treatment for stroke has become more common during recent years. It is unclear whether this carries an increased risk of postoperative complications and death. The aim of this nationwide population-based study was, therefore, to investigate the...


    pub_type: 杂志文章


    authors: Koraen-Smith L,Troëng T,Björck M,Kragsterman B,Wahlgren CM,Swedish Vascular Registry and the Riks-Stroke Collaboration.

    更新日期:2014-03-01 00:00:00

  • Efficacy and safety of vorapaxar in patients with prior ischemic stroke.

    abstract:BACKGROUND AND PURPOSE:Vorapaxar is an antiplatelet agent that antagonizes thrombin-mediated activation of the protease-activated receptor-1 on platelets. We tested the efficacy and safety of vorapaxar in a prespecified analysis in the stroke subcohort from a multinational, randomized, placebo-controlled trial. METHOD...


    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Morrow DA,Alberts MJ,Mohr JP,Ameriso SF,Bonaca MP,Goto S,Hankey GJ,Murphy SA,Scirica BM,Braunwald E,Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events–TIMI 50 Steering Committee and Investigators

    更新日期:2013-03-01 00:00:00

  • Delayed cerebellar infarction following a car accident.

    abstract::A patient developed a cerebellar infarction five weeks after a car accident. The pathophysiology and the medico-legal implications are discussed. ...


    pub_type: 杂志文章


    authors: Nichelli P,Gibertoni M,Guerzoni C

    更新日期:1983-07-01 00:00:00

  • The relevance of in vitro smooth muscle experiments to cerebral vasospasm.

    abstract::An overview of the possible factors that might contribute to the development of cerebral vasospasm is presented, with particular emphasis on the possibility that spasm arises from a malfunction of the regulatory or contractile processes in smooth muscle cells. This possibility is emphasized because the evidence for ce...


    pub_type: 杂志文章,评审


    authors: Wellum GR,Peterson JW,Zervas NT

    更新日期:1985-07-01 00:00:00

  • Prestroke modified rankin stroke scale has moderate interobserver reliability and validity in an acute stroke setting.

    abstract:BACKGROUND AND PURPOSE:The modified Rankin Scale (mRS) is the recommended functional outcome assessment in stroke trials. Utility of mRS may be limited by interobserver variability. prestroke function, described using mRS, is often used as trial entry criterion. We assessed the reliability and validity of prestroke mRS...


    pub_type: 杂志文章


    authors: Fearon P,McArthur KS,Garrity K,Graham LJ,McGroarty G,Vincent S,Quinn TJ

    更新日期:2012-12-01 00:00:00

  • Aneurysmal subarachnoid hemorrhage in Izumo City and Shimane Prefecture of Japan. Incidence.

    abstract::During the 5-year period from 1980 to 1984, the incidence of subarachnoid hemorrhage due only to rupture of aneurysms was investigated in Izumo City, a small city with a population of 79,026. Additionally, to ascertain the relation of incidence to the size of the geographic area and/or population, a similar analysis w...


    pub_type: 杂志文章


    authors: Inagawa T,Ishikawa S,Aoki H,Takahashi M,Yoshimoto H

    更新日期:1988-02-01 00:00:00

  • Influence of gender on K+-induced cerebral vasodilatation.

    abstract:BACKGROUND AND PURPOSE:It is not known whether cerebral vasoprotective mechanisms in females include increased function of arterial K+ channels. We hypothesized that vasodilator responses mediated by activation of inwardly rectifying K+ (K(IR)) channels are greater in cerebral arteries of female versus male rats and th...


    pub_type: 杂志文章


    authors: Chrissobolis S,Sobey CG

    更新日期:2004-03-01 00:00:00

  • Barthel index for stroke trials: development, properties, and application.

    abstract:BACKGROUND AND PURPOSE:Robust measures of functional outcome are required to determine treatment effects in stroke trials. Of the various measures available, the Barthel index (BI) is one of the more prevalent. We aimed to describe validity, reliability, and responsiveness (clinimetric properties) of the BI in stroke t...


    pub_type: 杂志文章,评审


    authors: Quinn TJ,Langhorne P,Stott DJ

    更新日期:2011-04-01 00:00:00

  • Vessel wall magnetic resonance imaging in acute ischemic stroke: effects of embolism and mechanical thrombectomy on the arterial wall.

    abstract:BACKGROUND AND PURPOSE:The aim of the study was to determine the effects of thromboembolism and mechanical thrombectomy on the vessel wall magnetic resonance imaging (VW-MRI) appearance of the intracranial arterial wall. METHODS:This was a cross-sectional study of consecutive patients with acute intracranial arterial ...


    pub_type: 杂志文章


    authors: Power S,Matouk C,Casaubon LK,Silver FL,Krings T,Mikulis DJ,Mandell DM

    更新日期:2014-08-01 00:00:00

  • Low concentration of serum total cholesterol is associated with multifocal signal loss lesions on gradient-echo magnetic resonance imaging: analysis of risk factors for multifocal signal loss lesions.

    abstract:BACKGROUND AND PURPOSE:Multifocal signal loss lesions (MSLLs) on T2*-weighted gradient-echo (GE) MRI are believed to be microbleeds histopathologically. Previous epidemiological studies suggested that low serum cholesterol is associated with the increased risk of intracerebral hemorrhage. We investigated risk factors o...


    pub_type: 临床试验,杂志文章


    authors: Lee SH,Bae HJ,Yoon BW,Kim H,Kim DE,Roh JK

    更新日期:2002-12-01 00:00:00

  • Arterial stiffness, cognitive decline, and risk of dementia: the Rotterdam study.

    abstract:BACKGROUND AND PURPOSE:Arterial stiffness is associated with an increased risk of myocardial infarction and stroke, independent of classical vascular risk factors. Vascular factors and stroke are associated with cognitive function and dementia. We examined whether arterial stiffness was independently associated with co...


    pub_type: 杂志文章


    authors: Poels MM,van Oijen M,Mattace-Raso FU,Hofman A,Koudstaal PJ,Witteman JC,Breteler MM

    更新日期:2007-03-01 00:00:00

  • Aggressive mechanical clot disruption: a safe adjunct to thrombolytic therapy in acute stroke?

    abstract:BACKGROUND AND PURPOSE:This study evaluated the safety and efficacy of aggressive mechanical clot disruption (AMCD) in acute stroke patients with persisting middle cerebral artery (MCA) or internal carotid artery (ICA) occlusion after thrombolytic therapy. METHODS:Retrospective case series were used from a prospective...


    pub_type: 杂志文章


    authors: Noser EA,Shaltoni HM,Hall CE,Alexandrov AV,Garami Z,Cacayorin ED,Song JK,Grotta JC,Campbell MS 3rd

    更新日期:2005-02-01 00:00:00

  • Risk Profile of Symptomatic Lacunar Stroke Versus Nonlobar Intracerebral Hemorrhage.

    abstract:BACKGROUND AND PURPOSE:Although lacunar stroke (LS) and deep intracerebral hemorrhage (dICH) represent acute manifestations of the same pathological process involving cerebral small vessels (small vessel disease), it remains unclear what factors predispose to one phenotype rather than the other at individual level. ME...


    pub_type: 杂志文章


    authors: Morotti A,Paciaroni M,Zini A,Silvestrelli G,Del Zotto E,Caso V,Dell'Acqua ML,Simone AM,Lanari A,Costa P,Poli L,De Giuli V,Gamba M,Ciccone A,Ritelli M,Di Castelnuovo A,Iacoviello L,Colombi M,Agnelli G,Grassi M,de G

    更新日期:2016-08-01 00:00:00

  • Baseline magnetic resonance imaging parameters and stroke outcome in patients treated by intravenous tissue plasminogen activator.

    abstract:BACKGROUND AND PURPOSE:We designed a prospective sequential pretreatment and posttreatment MRI study to assess the relation between neuroimaging parameters and clinical outcome in patients treated with intravenous recombinant tissue-type plasminogen activator (rtPA). METHODS:Patients with symptoms of acute hemispheric...


    pub_type: 临床试验,杂志文章


    authors: Nighoghossian N,Hermier M,Adeleine P,Derex L,Dugor JF,Philippeau F,Ylmaz H,Honnorat J,Dardel P,Berthezène Y,Froment JC,Trouillas P

    更新日期:2003-02-01 00:00:00

  • Effect of intracarotid prostaglandin E1 on regional cerebral blood flow in man.

    abstract::The effect of prostaglandin E1 on regional cerebral blood flow (rCBF) was studied with the intra-arterial 133Xe method in ten awake patients under local anesthesia. Measurements were taken from 16 areas of a hemisphere in seven patients, from 35 areas of a hemisphere in two patients and from 256 areas of a hemisphere ...


    pub_type: 杂志文章


    authors: Olesen J

    更新日期:1976-11-01 00:00:00

  • Knowledge about risk factors for stroke: a population-based survey with 28,090 participants.

    abstract:BACKGROUND AND PURPOSE:Increased knowledge of stroke risk factors in the general population may lead to improved prevention of stroke. The objective of the present study was to assess knowledge of stroke risk factors and to determine factors associated with knowledge. METHODS:In a population-based survey, we sent a qu...


    pub_type: 杂志文章


    authors: Müller-Nordhorn J,Nolte CH,Rossnagel K,Jungehülsing GJ,Reich A,Roll S,Villringer A,Willich SN

    更新日期:2006-04-01 00:00:00

  • Cellular actions of halothane on cat cerebral arterial muscle.

    abstract::The effects of halothane on intracellular membrane potential (Em) and force development in cat MCA were studied. Halothane (0.07-0.14 mM/1) relaxed isolated MCA which had developed myogenic tone. Measurement of Em showed that halothane depolarized this preparation in a dose-dependent fashion in the face of vessel rela...


    pub_type: 杂志文章


    authors: Harder DR,Gradall K,Madden JA,Kampine JP

    更新日期:1985-07-01 00:00:00