Abstract:
OBJECTIVE:Degeneration of chronically demyelinated axons is a major cause of irreversible neurological decline in the human central nervous system disease, multiple sclerosis (MS). Although the molecular mechanisms responsible for this axonal degeneration remain to be elucidated, dysfunction of axonal Na+/K+ ATPase is thought to be central. To date, however, the distribution of Na+/K+ ATPase has not been studied in MS lesions. METHODS:The percentage of axons with detectable Na+/K+ ATPase was determined in 3 acute and 36 chronically demyelinated lesions from 13 MS brains. In addition, we investigated whether postmortem magnetic resonance imaging profiles could predict Na+/K+ ATPase immunostaining in a subset (20) of the chronic lesions. RESULTS:Na+/K+ ATPase subunits alpha1, alpha3, and beta1 were detected in the internodal axolemma of myelinated fibers in both control and MS brains. In acutely demyelinated lesions, Na+/K+ ATPase was detectable on demyelinated axolemma. In contrast, 21 of the 36 chronic lesions (58%) contained less than 50% Na+/K+ ATPase-positive demyelinated axons. In addition, magnetic resonance imaging-pathology correlations of 20 chronic lesions identified a linear decrease in the percentage of Na+/K+ ATPase-positive axons and magnetization transfer ratios (p < 0.0001) and T1 contrast ratios (p < 0.0006). INTERPRETATION:Chronically demyelinated axons that lack Na+/K+ ATPase cannot exchange axoplasmic Na+ for K+ and are incapable of nerve transmission. Loss of axonal Na+/K+ ATPase is likely to be a major contributor to continuous neurological decline in chronic stages of MS, and quantitative magnetization transfer ratios and T1 contrast ratios may provide a noninvasive surrogate marker for monitoring this loss in MS patients.
journal_name
Ann Neuroljournal_title
Annals of neurologyauthors
Young EA,Fowler CD,Kidd GJ,Chang A,Rudick R,Fisher E,Trapp BDdoi
10.1002/ana.21381subject
Has Abstractpub_date
2008-04-01 00:00:00pages
428-35issue
4eissn
0364-5134issn
1531-8249journal_volume
63pub_type
杂志文章abstract::Copper toxicity contributes to neuronal death in Wilson's disease and has been speculatively linked to the pathogenesis of Alzheimer's and prion diseases. We examined copper-induced neuronal death with the goal of developing neuroprotective strategies. Copper catalyzed an increase in hydroxyl radical generation in sol...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.10276
更新日期:2002-08-01 00:00:00
abstract::A case-control study was performed to determine the possible roles of various environmental factors, prior illnesses, drug use, and personal habits in the development of Alzheimer's disease. Such information was collected from 40 patients with onset of dementia prior to age 70 and from 80 community control subjects ma...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410150406
更新日期:1984-04-01 00:00:00
abstract::We report the use of a new stable isotope-labeled form of levodopa (LD) to examine in vivo central LD metabolism in Parkinson's disease (PD). Eight patients representing a wide spectrum of disease severity were administered 50 mg of carbidopa orally followed in 1 hour by an intravenous bolus of 150 mg of stable isotop...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410420305
更新日期:1997-09-01 00:00:00
abstract::We studied the in vitro electrical activity of rat neostriatal neurons following chronic neuroleptic treatment. In haloperidol-treated rats, unlike naive animals, activation of neostriatal D2 dopamine receptors induced a potent presynaptic inhibition of glutamate-mediated excitatory synaptic potentials. Haloperidol tr...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410310404
更新日期:1992-04-01 00:00:00
abstract::The incidence of periventricular-intraventricular hemorrhage (PV-IVH) in a group of 460 preterm infants with birth weight less than 2,250 gm, studied by cranial ultrasonography, was 39%. Sixty-four (36%) of the infants with periventricular-intraventricular hemorrhage had, in addition, periventricular intraparenchymal ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410150315
更新日期:1984-03-01 00:00:00
abstract::We describe the clinical and oculographic findings in 4 families with episodic ataxia and interictal nystagmus (EA-2) linked to chromosome 19p. Episodes varied from pure ataxia to combinations of symptoms suggesting involvement of the cerebellum, brainstem, and cortex. Some affected individuals exhibited a progressive...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410410105
更新日期:1997-01-01 00:00:00
abstract::Two recent case-control studies have suggested a strong association of a missense polymorphism in exon 2 of the cathepsin D gene (CTSD) and Alzheimer disease (AD). However, these findings were not confirmed in another independent study. We analyzed this polymorphism in two large and independent AD study populations an...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/1531-8249(200101)49:1<114::aid-ana18>3.0.c
更新日期:2001-01-01 00:00:00
abstract::After unilateral cortical lesions in neonatal rats, the spared unablated hemisphere is known to demonstrate remarkable neuroanatomical plasticity in corticofugal connectivity. This same type of structural plasticity is not seen after similar lesions in adult rats. One possibility for the lack of such a plastic respons...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/1531-8249(199906)45:6<778::aid-ana12>3.0.c
更新日期:1999-06-01 00:00:00
abstract:OBJECTIVE:To investigate whether phospholipase A2 (PLA2) plays a role in the pathogenesis of spinal cord injury (SCI). METHODS:Biochemical, Western blot, histological, immunohistochemical, electron microscopic, electrophysiological, and behavior assessments were performed to investigate (1) SCI-induced PLA2 activity, ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.20798
更新日期:2006-04-01 00:00:00
abstract:OBJECTIVES:African Americans are at greater risk for developing Alzheimer's disease (AD) dementia than non-Hispanic whites. In addition to biological considerations (eg, genetic influences and comorbid disorders), social and environmental factors may increase the risk of AD dementia. This paper (1) assesses neuroimagin...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.25948
更新日期:2021-02-01 00:00:00
abstract::Results of case-control studies and of a prospective investigation in men suggest that consumption of coffee could protect against the risk of Parkinson's disease, but the active constituent is not clear. To address the hypothesis that caffeine is protective against Parkinson's disease, we examined the relationship of...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.1052
更新日期:2001-07-01 00:00:00
abstract::Neurotrophic factors have been demonstrated to prevent the development of peripheral neuropathy in animal models, but the therapeutic use of these factors in human disease has been limited by the short serum half-life and dose-limiting side effects of these potent peptides. We used peripheral subcutaneous inoculation ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.10061
更新日期:2002-01-01 00:00:00
abstract::Positron emission tomography (PET) of glucose metabolism is often applied for the localization of epileptogenic brain regions, but hypometabolic areas are often larger than or can miss epileptogenic cortex in nonlesional neocortical epilepsy. The present study is a three-dimensional brain surface analysis designed to ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:
更新日期:2000-07-01 00:00:00
abstract::Patients with multiple sclerosis (MS) frequently have selective depletion of the CD45R+CD4+ T-cell subset during active phases of disease. To study the relationship between changes in this subset and the onset of objective clinical exacerbations of disease, a longitudinal study was undertaken. Two CD4+ T-cell subsets ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410240204
更新日期:1988-08-01 00:00:00
abstract::We sought to determine whether medullary serotonergic neurons were affected in multiple system atrophy (MSA). Immunostaining for tryptophan hydroxylase was performed on serial 50 microm sections of the medulla of brains obtained at autopsy from six control subjects, eight subjects with clinical diagnosis of MSA, and f...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.20021
更新日期:2004-03-01 00:00:00
abstract::Latency measurements between three potentials (waves I, III, and IV/V) of the human brainstem auditory response can allow early detection of certain posterior fossa lesions. The diagnostic use of these interwave latencies requires knowledge of what factors may prolong them in the absence of disease. Hypothermia appear...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410030416
更新日期:1978-04-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章,多中心研究
doi:10.1002/ana.25545
更新日期:2019-09-01 00:00:00
abstract::Regular, evidence-based assignment of patients to etiologic stroke categories is essential to enable valid comparison among studies. We designed an algorithm (SSS-TOAST) that incorporated recent advances in stroke imaging and epidemiology to identify the most probable TOAST category in the presence of evidence for mul...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.20617
更新日期:2005-11-01 00:00:00
abstract::Mutations in genes encoding the NADH ubiquinone oxidoreductase, complex I of the respiratory chain, cause a diverse group of diseases. They include Leber hereditary optic neuropathy, Leigh syndrome, and mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes. There is no effective treatment for t...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.20175
更新日期:2004-08-01 00:00:00
abstract:OBJECTIVE:Prolonged human immunodeficiency virus-1 (HIV-1) infection leads to neurological debilitation, including motor dysfunction and frank dementia. Although pharmacological control of HIV infection is now possible, HIV-associated neurocognitive disorders (HAND) remain intractable. Here, we report that chronic trea...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.22070
更新日期:2010-09-01 00:00:00
abstract::Although the basal ganglia have been implicated in the development of movement disorders since the 1940s, the exact role played by these structures has remained elusive. The development of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-monkey model of parkinsonism, and the recent resurgence of surgical therapy for t...
journal_title:Annals of neurology
pub_type: 杂志文章,评审
doi:
更新日期:2000-04-01 00:00:00
abstract:OBJECTIVE:To determine the presence and kinetics of antibodies against synaptic proteins in patients with herpes simplex virus encephalitis (HSE). METHODS:Retrospective analysis of 44 patients with polymerase chain reaction-proven HSE for the presence of a large panel of onconeuronal and synaptic receptor antibodies. ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.23689
更新日期:2012-12-01 00:00:00
abstract::The neurodiagnostic criteria of Leigh syndrome have not yet been clearly redefined based on the expanding of molecular etiologies. We aimed to analyze 20 years of clinical, genetic, and magnetic resonance studies from our Leigh syndrome cohort to provide a detailed description of central nervous system lesions in Leig...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.25789
更新日期:2020-08-01 00:00:00
abstract::Friedreich's ataxia (FA) is the most frequently inherited ataxia. To test the hypothesis that iron is increased in the cerebellum of patients with FA, we developed a multigradient echo magnetic resonance sequence for the three-dimensional imaging of brain iron-induced contrast. Relaxation rate (R2*) values in the unaf...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/1531-8249(199907)46:1<123::aid-ana19>3.0.c
更新日期:1999-07-01 00:00:00
abstract:OBJECTIVE:Amyotrophic lateral sclerosis (ALS) is a motor neuron disease whose pathophysiological deficits, causing impairment in motor function, are largely unknown. Here we propose that hydrogen sulfide (H2 S), as a glial-released inflammatory factor, contributes to ALS-mediated motor neuron death. METHODS:H2 S conce...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.24372
更新日期:2015-04-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410040605
更新日期:1978-12-01 00:00:00
abstract::Although the cause of multiple sclerosis (MS) has remained obscure, many findings support an autoimmune pathogenesis on the background of a complex interaction between multiple genes and environmental factors. Accordingly, targeting the immune system has been a rational approach for the treatment of MS. The developmen...
journal_title:Annals of neurology
pub_type: 杂志文章,评审
doi:10.1002/ana.21289
更新日期:2007-10-01 00:00:00
abstract::Blood gene expression profiling has been applied to a variety of hematological malignancies, autoimmune disorders, and infectious diseases. This study applies this approach to genetic diseases without obvious blood phenotypes. Three genetic diseases including tuberous sclerosis complex 2, neurofibromatosis type 1, and...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.20291
更新日期:2004-12-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章,评审
doi:10.1002/ana.10628
更新日期:2003-01-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410260512
更新日期:1989-11-01 00:00:00