Brain haemosiderin in older people: pathological evidence for an ischaemic origin of magnetic resonance imaging (MRI) microbleeds.

Abstract:

INTRODUCTION:Magnetic resonance imaging (MRI) cerebral microbleeds (CMB) arise from ferromagnetic haemosiderin iron assumed to derive from extravasation of erythrocytes. Light microscopy of ageing brain frequently reveals foci of haemosiderin from single crystalloids to larger, predominantly perivascular, aggregates. The pathological and radiological relationship between these findings is not resolved. METHODS:Haemosiderin deposition and vascular pathology in the putamen were quantified in 200 brains donated to the population-representative Medical Research Council Cognitive Function and Ageing Study. Molecular markers of gliosis and tissue integrity were assessed by immunohistochemistry in brains with highest (n = 20) and lowest (n = 20) levels of putamen haemosiderin. The association between haemosiderin counts and degenerative and vascular brain pathology, clinical data, and the haemochromatosis (HFE) gene H63D genotype were analysed. The frequency of MRI CMB in 10 cases with highest and lowest burden of putamen haemosiderin, was compared using post mortem 3T MRI. RESULTS:Greater putamen haemosiderin was significantly associated with putaminal indices of small vessel ischaemia (microinfarcts, P < 0.05; arteriolosclerosis, P < 0.05; perivascular attenuation, P < 0.001) and with lacunes in any brain region (P < 0.023) but not large vessel disease, or whole brain measures of neurodegenerative pathology. Higher levels of putamen haemosiderin correlated with more CMB (P < 0.003). CONCLUSIONS:The MRI-CMB concept should take account of brain iron homeostasis, and small vessel ischaemic change in later life, rather than only as a marker for minor episodes of cerebrovascular extravasation. These data are of clinical relevance, suggesting that basal ganglia MRI microbleeds may be a surrogate for ischaemic small vessel disease rather than exclusively a haemorrhagic diathesis.

authors

Janaway BM,Simpson JE,Hoggard N,Highley JR,Forster G,Drew D,Gebril OH,Matthews FE,Brayne C,Wharton SB,Ince PG,MRC Cognitive Function and Ageing Neuropathology Study.

doi

10.1111/nan.12062

subject

Has Abstract

pub_date

2014-04-01 00:00:00

pages

258-69

issue

3

eissn

0305-1846

issn

1365-2990

journal_volume

40

pub_type

杂志文章
  • Comparative analysis of mRNA levels in the frontal cortex and the hippocampus in the basal state and in response to experimental brain injury.

    abstract::Damage to the frontal cortex and to the hippocampus, both in terms of cell loss and neuronal dysfunction, is thought to underlie many of the neurological and behavioural consequences of traumatic brain injury (TBI). Several studies have indicated that the hippocampus is particularly susceptible to central nervous syst...

    journal_title:Neuropathology and applied neurobiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2990.2003.00439.x

    authors: Rall JM,Matzilevich DA,Dash PK

    更新日期:2003-04-01 00:00:00

  • The organization of astrocytes in organotypic mouse spinal cord culture: an electron microscope study.

    abstract::The organization of astrocytes in myelinated culture of mouse spinal cord tissue was analysed ultrastructurally and compared with the pattern in vivo. Astrocyte cell bodies and their processes, connected by punctate adhesions and gap junctions, formed a continuous layer around the entire explant. Throughout the parenc...

    journal_title:Neuropathology and applied neurobiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2990.1984.tb00390.x

    authors: Kusaka H,Hirano A,Bornstein MB,Raine CS

    更新日期:1984-11-01 00:00:00

  • Loss of neurofibromatosis 1 (NF1) gene expression in NF1-associated pilocytic astrocytomas.

    abstract::The critical role of the neurofibromatosis 1 (NF1) gene as a tumour suppressor has been clearly demonstrated for malignancies arising in NF1 patients. However, little is known about the more common benign tumours, such as the pilocytic astrocytoma. Most NF1-associated astrocytomas are benign and clinically non-progres...

    journal_title:Neuropathology and applied neurobiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2990.2000.00258.x

    authors: Gutmann DH,Donahoe J,Brown T,James CD,Perry A

    更新日期:2000-08-01 00:00:00

  • RAPGEF2 mediates oligomeric Aβ-induced synaptic loss and cognitive dysfunction in the 3xTg-AD mouse model of Alzheimer's disease.

    abstract:AIMS:Amyloid-β (Aβ) oligomers trigger synaptic degeneration that precedes plaque and tangle pathology. However, the signalling molecules that link Aβ oligomers to synaptic pathology remain unclear. Here, we addressed the potential role of RAPGEF2 as a novel signalling molecule in Aβ oligomer-induced synaptic and cognit...

    journal_title:Neuropathology and applied neurobiology

    pub_type: 杂志文章

    doi:10.1111/nan.12686

    authors: Jang YN,Jang H,Kim GH,Noh JE,Chang KA,Lee KJ

    更新日期:2020-12-20 00:00:00

  • The effects of pre-natal exposure to methylazoxymethanol acetate on microglia.

    abstract::The effects of exposure to a cytotoxic agent, methylazoxymethanol acetate (MAM Ac), on the distribution, density and quantitative morphology of microglia in the rat forebrain have been examined with the aid of a peroxidase-conjugated lectin derived from Griffonia simplicifolia. Following exposure to MAM Ac (25 mg/kg m...

    journal_title:Neuropathology and applied neurobiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2990.1992.tb00832.x

    authors: Ashwell KW

    更新日期:1992-12-01 00:00:00

  • A case of Pelizaeus-Merzbacher disease showing increased dosage of the proteolipid protein gene.

    abstract::Clinical, neuropathological and molecular genetic studies in a 9 month old boy with Pelizaeus-Merzbacher disease are described. The principal clinical features were developmental delay, nystagmus, stridor and seizures. Both brain and spinal cord showed almost complete absence of stainable central myelin, while cranial...

    journal_title:Neuropathology and applied neurobiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2990.1995.tb01036.x

    authors: Harding B,Ellis D,Malcolm S

    更新日期:1995-04-01 00:00:00

  • Hirano body-rich subtypes of Creutzfeldt-Jakob disease.

    abstract:BACKGROUND:In definite Creutzfeldt-Jakob disease (CJD), morphological and immunohistochemical patterns are useful to identify molecular subtypes. Severe cerebellar pathology and hippocampal involvement helps to identify VV subtypes. The rare VV1 variant (<1%), more frequent in young individuals, is additionally charact...

    journal_title:Neuropathology and applied neurobiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2990.2011.01208.x

    authors: Martinez-Saez E,Gelpi E,Rey MJ,Ferrer I,Ribalta T,Botta-Orfila T,Nos C,Yagüe J,Sanchez-Valle R

    更新日期:2012-04-01 00:00:00

  • Review: The role of mitochondria in the pathogenesis of amyotrophic lateral sclerosis.

    abstract::Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by loss of upper and lower motor neurones leading to muscle weakness and paralysis. Despite recent advances in the genetics of ALS, the mechanisms underlying motor neurone degeneration are not fully understood. Mitochondria are know...

    journal_title:Neuropathology and applied neurobiology

    pub_type: 杂志文章,评审

    doi:10.1111/j.1365-2990.2011.01166.x

    authors: Duffy LM,Chapman AL,Shaw PJ,Grierson AJ

    更新日期:2011-06-01 00:00:00

  • Ageing causes prominent neurovascular dysfunction associated with loss of astrocytic contacts and gliosis.

    abstract:AIMS:Normal neurovascular coupling, mediated by the fine interplay and communication of cells within the neurovascular unit, is critical for maintaining normal brain activity and cognitive function. This study investigated whether, with advancing age there is disruption of neurovascular coupling and specific cellular c...

    journal_title:Neuropathology and applied neurobiology

    pub_type: 杂志文章

    doi:10.1111/nan.12375

    authors: Duncombe J,Lennen RJ,Jansen MA,Marshall I,Wardlaw JM,Horsburgh K

    更新日期:2017-10-01 00:00:00

  • Hemiparkinsonism with infarction of the ipsilateral substantia nigra.

    abstract::An elderly man suffering from dementia associated with hypertension developed right-sided parkinsonism marked by rigidity and flexion. At autopsy the brain showed generalized vascular changes chiefly in the white matter, diffuse plaque and neurofibrillary tangle formation in the temporal cortex, and a discrete gliotic...

    journal_title:Neuropathology and applied neurobiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2990.1978.tb00548.x

    authors: Hunter R,Smith J,Thomson T,Dayan AD

    更新日期:1978-07-01 00:00:00

  • The role of cytochrome c oxidase deficient hippocampal neurones in Alzheimer's disease.

    abstract::Defects of mitochondrial function have been proposed as a potential mechanism in the development and pathogenesis of Alzheimer's disease (AD) and neuronal apoptosis. Mitochondrial enzyme-deficient pyramidal neurones are found in greater quantities in the hippocampus of AD patients than in age-matched controls. The pre...

    journal_title:Neuropathology and applied neurobiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2990.2002.00414.x

    authors: Cottrell DA,Borthwick GM,Johnson MA,Ince PG,Turnbull DM

    更新日期:2002-10-01 00:00:00

  • Vascular endothelial growth factor and the nervous system.

    abstract::Vascular endothelial growth factor (VEGF) is an angiogenic factor essential for the formation of new blood vessels during embryogenesis and in many pathological conditions. A new role for VEGF as a neurotrophic factor has recently emerged. In the developing nervous system, VEGF plays a pivotal role not only in vascula...

    journal_title:Neuropathology and applied neurobiology

    pub_type: 杂志文章,评审

    doi:10.1111/j.1365-2990.2004.00600.x

    authors: Brockington A,Lewis C,Wharton S,Shaw PJ

    更新日期:2004-10-01 00:00:00

  • Ultrastructural localization of adhalin, alpha-dystroglycan and merosin in normal and dystrophic muscle.

    abstract::Adhalin and alpha-dystroglycan are two components of a complex of proteins that, in conjunction with dystrophin, provide a link between the subsarcolemmal cytoskeleton and the basal lamina of the extracellular matrix of skeletal muscle. In the absence of dystrophin, in Duchenne muscular dystrophy (DMD) and the mdx mou...

    journal_title:Neuropathology and applied neurobiology

    pub_type: 杂志文章

    doi:

    authors: Cullen MJ,Walsh J,Roberds SL,Campbell KP

    更新日期:1996-02-01 00:00:00

  • Can the BB-rat help to unravel diabetic neuropathy?

    abstract::Diabetic neuropathy is probably the most common and one of the most disabling complications of diabetes mellitus. Although several possible pathogenetic mechanisms for this complication have been suggested, they cannot easily be tested in man. Therefore animal models with induced or spontaneous onset of diabetes melli...

    journal_title:Neuropathology and applied neurobiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2990.1985.tb00023.x

    authors: Sima AA

    更新日期:1985-07-01 00:00:00

  • Sclerosing meningioma: immunohistochemical analysis of five cases.

    abstract::Sclerosing meningioma is a rare morphologic subtype of meningioma and may be mistaken for atypical or malignant meningioma and astrocytoma or schwannoma because of marked collagen deposits and a sparse population of cells with little resemblance to meningothelial cells. Authors describe the histopathologic and immunop...

    journal_title:Neuropathology and applied neurobiology

    pub_type: 杂志文章

    doi:10.1046/j.0305-1846.2003.00517.x

    authors: Kim NR,Im SH,Chung CK,Suh YL,Choe G,Chi JG

    更新日期:2004-04-01 00:00:00

  • Neonatal rat model of intraventricular haemorrhage and post-haemorrhagic ventricular dilatation with long-term survival into adulthood.

    abstract:AIMS:post-haemorrhagic ventricular dilatation (PHVD) is a significant problem in neonatal care, with sequelae extending beyond childhood. Its management is important in determining outcome. Although rodent hydrocephalus models have been developed, PHVD, as a specific entity with a distinct pathophysiology, has not been...

    journal_title:Neuropathology and applied neurobiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2990.2010.01118.x

    authors: Aquilina K,Chakkarapani E,Love S,Thoresen M

    更新日期:2011-02-01 00:00:00

  • Endothelial changes in muscle and skin biopsies in patients with CADASIL.

    abstract::Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is characterized by the deposition of granular osmiophilic material in association with vascular smooth muscle cells in many different organs. However, the cause of the subsequent destruction of smooth muscle cells tha...

    journal_title:Neuropathology and applied neurobiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2990.1998.00087.x

    authors: Ruchoux MM,Maurage CA

    更新日期:1998-02-01 00:00:00

  • Differential expression of phosphorylated translation initiation factor 2 alpha in Alzheimer's disease and Creutzfeldt-Jakob's disease.

    abstract::Studies in vitro have shown that phosphorylated translation initiation factor 2 alpha (TIF 2 alpha) may have several functions, including regulation of protein synthesis, control of cell death and procurement of resistance to oxidative stress in nerve cells. These properties may have implications in certain human neur...

    journal_title:Neuropathology and applied neurobiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2990.2002.t01-1-00410.x

    authors: Ferrer I

    更新日期:2002-12-01 00:00:00

  • Increased production of ubiquitin mRNA in motor neurons after axotomy.

    abstract::Ubiquitin targets proteins for attack by certain proteolytic enzymes, but the ubiquitinated cytoplasmic inclusions seen in some chronic neurodegenerative diseases may indicate the occurrence of reparative rather than destructive metabolic events. We have examined the production of ubiquitin in motor neurons of the rat...

    journal_title:Neuropathology and applied neurobiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2990.1994.tb01012.x

    authors: Savedia S,Kiernan JA

    更新日期:1994-12-01 00:00:00

  • Historical survey. The concept of a sensorimotor cortex: its later history during the twentieth century.

    abstract::This paper continues the historical review on the concept of a sensorimotor cortex into the twentieth century. Paul Flechsig was probably the first to accept this concept after the turn of the century. Like Munk, he believed in an almost reflex-like unity between cortical sensory and motor function. With the help of h...

    journal_title:Neuropathology and applied neurobiology

    pub_type: 历史文章,杂志文章

    doi:10.1111/j.1365-2990.1982.tb00264.x

    authors: Meyer A

    更新日期:1982-03-01 00:00:00

  • Steroid hormone receptors in pituitary adenomas: a biochemical, immunohistochemical and morphometric study on cryostat sections.

    abstract::Oestrogen receptors and progesterone receptors were measured by an isoelectric focussing technique in cytosols from cryostat sections of eight human pituitary adenomas. Cryostat sections adjacent to the assayed sample were stained for anterior pituitary hormones using the peroxidase-antiperoxidase technique, and the c...

    journal_title:Neuropathology and applied neurobiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2990.1986.tb00158.x

    authors: Ironside JW,Dangerfield VJ,Timperley WR,Underwood JC

    更新日期:1986-11-01 00:00:00

  • 14,15-epoxyeicosatrienoic acid promotes production of brain derived neurotrophic factor from astrocytes and exerts neuroprotective effects during ischaemic injury.

    abstract:AIMS:14,15-Epoxyeicosatrienoic acid (14,15-EET) is abundantly expressed in brain and exerts protective effects against ischaemia. 14,15-EET is hydrolysed by soluble epoxide hydrolase (sEH). sEH-/- mice show a higher level of 14,15-EET in the brain. Astrocytes play a pivotal role in neuronal survival under ischaemic con...

    journal_title:Neuropathology and applied neurobiology

    pub_type: 杂志文章

    doi:10.1111/nan.12291

    authors: Yuan L,Liu J,Dong R,Zhu J,Tao C,Zheng R,Zhu S

    更新日期:2016-12-01 00:00:00

  • Reduction and the intracellular translocation of EphB2 in Tg2576 mice and the effects of β-amyloid.

    abstract:AIMS:EphB2 is a member of receptor tyrosine kinases (RTKs) family that is essential for the cell adhesion, neural crest migration, axon guidance and synaptogenesis in the nervous system. Recent studies show that preservation of EphB2 in a transgenic mouse model of Alzheimer's disease (AD) rescues the cognitive deficit,...

    journal_title:Neuropathology and applied neurobiology

    pub_type: 杂志文章

    doi:10.1111/nan.12019

    authors: Qu M,Jiang J,Liu XP,Tian Q,Chen LM,Yin G,Liu D,Wang JZ,Zhu LQ

    更新日期:2013-10-01 00:00:00

  • Neuropathology of the chronic epileptic syndrome induced by intrahippocampal tetanus toxin in rat: preservation of pyramidal cells and incidence of dark cells.

    abstract::A few nanograms of tetanus toxin injected into a rat hippocampus causes a chronic epileptic syndrome characterized by brief seizures that recur intermittently for about 6 weeks. Cognitive and other behavioural impairments persist after the seizures and other epileptic electrographic activity have remitted, and may be ...

    journal_title:Neuropathology and applied neurobiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2990.1992.tb00764.x

    authors: Jefferys JG,Evans BJ,Hughes SA,Williams SF

    更新日期:1992-02-01 00:00:00

  • Absence of neuronal nitric oxide synthase (nNOS) as a pathological marker for the diagnosis of Becker muscular dystrophy with rod domain deletions.

    abstract::Immunohistochemistry using antibodies to dystrophin is the pathological basis for the diagnosis of Duchenne and Becker muscular dystrophy (DMD and BMD). While the sarcolemma of DMD muscle is negative, BMD muscle generally shows variable labelling because of the translation of a partially functional dystrophin that is ...

    journal_title:Neuropathology and applied neurobiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2990.2004.00561.x

    authors: Torelli S,Brown SC,Jimenez-Mallebrera C,Feng L,Muntoni F,Sewry CA

    更新日期:2004-10-01 00:00:00

  • Invited Review: Emerging functions of histone H3 mutations in paediatric diffuse high-grade gliomas.

    abstract::Paediatric diffuse high-grade gliomas (pHGG) are rare, but deadly tumours. The discovery of recurrent mutations in the tail of histone H3, changing lysine 27 to methionine, or glycine 34 to arginine or valine, has illuminated a critical role for epigenetic dysregulation in the aetiology of childhood gliomas and opened...

    journal_title:Neuropathology and applied neurobiology

    pub_type: 杂志文章,评审

    doi:10.1111/nan.12591

    authors: Kasper LH,Baker SJ

    更新日期:2020-02-01 00:00:00

  • Immunolocalization of cathepsin D in the human central nervous system and central nervous system neoplasms.

    abstract::The cellular distribution of the lysosomal proteinase cathepsin D was studied in a series of 76 neoplasms and 18 non-neoplastic tissues from the human central nervous system, using a well-characterized polyclonal antibody in a peroxidase-antiperoxidase technique. In the normal and developing brain, cathepsin D is conf...

    journal_title:Neuropathology and applied neurobiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2990.1990.tb00930.x

    authors: Robson DK,Ironside JW,Reid WA,Bogue PR

    更新日期:1990-02-01 00:00:00

  • The microglial/macrophagic response at the tumour-brain border of invasive meningiomas.

    abstract:AIMS:Little is known about the immune response of the brain to invasive meningiomas. The present study was based upon the hypothesis that the microglial/macrophagic response towards brain-invasive meningiomas is dependent on the intactness of the pial-glial basement membrane. METHODS:We immunostained sections from 40 ...

    journal_title:Neuropathology and applied neurobiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2990.2008.00960.x

    authors: Grund S,Schittenhelm J,Roser F,Tatagiba M,Mawrin C,Kim YJ,Bornemann A

    更新日期:2009-02-01 00:00:00

  • Adaptation of tibial nerve myelinated fibre parameters to reduced limb length caused by irradiation.

    abstract::Irradiation of a rat hind limb at 15 days of age caused marked shortening of the limb, with a consequent reduction in nerve length. The tibial nerves of the irradiated limbs were examined qualitatively and quantitatively, and compared with the unirradiated nerve. There was no evidence of fibre degeneration and only ve...

    journal_title:Neuropathology and applied neurobiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2990.1993.tb00404.x

    authors: Jacobs JM,Myers R

    更新日期:1993-02-01 00:00:00

  • Evidence that transmissible mink encephalopathy agent is biologically inactive in mice.

    abstract::Transmissible mink encephalopathy (TME) is probably a form of the sheep disease, scrapie, introduced by accidentally feeding mink with scrapie-infected sheep tissues. Although no successful transmissions of TME to mice have been achieved previous work has involved various limitations. To maximize the possibility of tr...

    journal_title:Neuropathology and applied neurobiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2990.1986.tb00051.x

    authors: Taylor DM,Dickinson AG,Fraser H,Marsh RF

    更新日期:1986-03-01 00:00:00