Abstract:
OBJECTIVE:Reducing levels of the microtubule-associated protein tau has shown promise as a potential treatment strategy for diseases with secondary epileptic features such as Alzheimer disease. We wanted to determine whether tau reduction may also be of benefit in intractable genetic epilepsies. METHODS:We studied a mouse model of Dravet syndrome, a severe childhood epilepsy caused by mutations in the human SCN1A gene encoding the voltage-gated sodium channel subunit Nav 1.1. We genetically deleted 1 or 2 Tau alleles in mice carrying an Nav 1.1 truncation mutation (R1407X) that causes Dravet syndrome in humans, and examined their survival, epileptic activity, related hippocampal alterations, and behavioral abnormalities using observation, electroencephalographic recordings, acute slice electrophysiology, immunohistochemistry, and behavioral assays. RESULTS:Tau ablation prevented the high mortality of Dravet mice and reduced the frequency of spontaneous and febrile seizures. It reduced interictal epileptic spikes in vivo and drug-induced epileptic activity in brain slices ex vivo. Tau ablation also prevented biochemical changes in the hippocampus indicative of epileptic activity and ameliorated abnormalities in learning and memory, nest building, and open field behaviors in Dravet mice. Deletion of only 1 Tau allele was sufficient to suppress epileptic activity and improve survival and nesting performance. INTERPRETATION:Tau reduction may be of therapeutic benefit in Dravet syndrome and other intractable genetic epilepsies.
journal_name
Ann Neuroljournal_title
Annals of neurologyauthors
Gheyara AL,Ponnusamy R,Djukic B,Craft RJ,Ho K,Guo W,Finucane MM,Sanchez PE,Mucke Ldoi
10.1002/ana.24230subject
Has Abstractpub_date
2014-09-01 00:00:00pages
443-56issue
3eissn
0364-5134issn
1531-8249journal_volume
76pub_type
杂志文章abstract::A patient is described who suffered a bilateral hemorrhagic infarction in the parasagittal cerebrum following neonatal asphyxia. This case confirms experimental results that show the parasagittal cerebrum is especially vulnerable to ischemic damage in newborns. ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410210215
更新日期:1987-02-01 00:00:00
abstract:OBJECTIVE:Lymphocytic choriomeningitis virus (LCMV) is a human pathogen and an emerging neuroteratogen. When the infection occurs during pregnancy, the virus can target and damage the fetal brain and retina. We examined the spectrum of clinical presentations, neuroimaging findings, and clinical outcomes of children wit...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.21161
更新日期:2007-10-01 00:00:00
abstract::A dinucleotide repeat polymorphism in a tau intron was identified and used in a case-control study to analyze the genetic association of tau with several neurodegenerative diseases with tau pathology. Subjects with the homozygous tau AO alleles were excessively represented in the progressive supranuclear palsy (PSP) g...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410410222
更新日期:1997-02-01 00:00:00
abstract:OBJECTIVE:Myasthenia gravis (MG), a neuromuscular disease mediated by anti-acetylcholine receptor (AChR) autoantibodies, is associated with thymic hyperplasia characterized by ectopic germinal centers that contain pathogenic antibody-producing B cells. Our thymic transcriptome study demonstrated increased expression of...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.21628
更新日期:2009-10-01 00:00:00
abstract::To investigate the potential role of drug therapy in preventing or exacerbating seizure-related brain injury in the prepubescent brain, we administered kainic acid to rats at postnatal day 35. Therapy with daily phenobarbital was started directly before or 1 day after kainic acid was administered, and was continued th...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410360314
更新日期:1994-09-01 00:00:00
abstract::Fifteen drug-free patients with early to midstage Huntington's disease were evaluated with quantitative neurological examinations, scales for functional capacity, computed tomographic (CT) scans, and positron emission tomographic (PET) scans of 18F-2-fluoro-2-deoxyglucose (18F-FDG) uptake. All patients had abnormal in...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410200305
更新日期:1986-09-01 00:00:00
abstract::The mucopolysaccharidoses are caused by inherited deficiencies of lysosomal enzymes involved in the degradative pathway of glycosaminoglycans. Lysosomal storage leads to cellular and organ dysfunction, including mental retardation. Storage lesions are found throughout the diseased brain, but little is known about the ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.10373
更新日期:2002-12-01 00:00:00
abstract::The purpose of this study was to determine the role of high-resolution T2-weighted fast multiplanar inversion-recovery (FMPIR) magnetic resonance (MR) imaging in detecting and delineating microscopic focal cortical dysplasia (FCD). We performed MR scans with FMPIR on 42 patients with suspected neocortical epilepsy. Te...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410440508
更新日期:1998-11-01 00:00:00
abstract::In a patient with acquired immunodeficiency disease syndrome (AIDS) and muscle weakness, a muscle biopsy specimen disclosed degeneration of muscle fibers, regeneration, and focal endomysial mononuclear inflammation. A conspicuous feature was the presence of perivascular macrophages within the endomysium that showed po...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410280418
更新日期:1990-10-01 00:00:00
abstract::Using two-color flow cytometric analysis, we studied peripheral blood lymphocyte subsets in 15 patients with human T-cell lymphotropic virus type I-associated myelopathy. The percentage of CD4+ 4B4+ cells (helper inducer T cell) was significantly increased in the patients with the myelopathy, compared with 16 healthy ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410260212
更新日期:1989-08-01 00:00:00
abstract::A young man presented with apparent transient ischemic attacks following a motorcycle accident in which he sustained minor injuries only. Computerized axial tomography demonstrated a small right frontal infarct, and angiography revealed an aneurysm of the right internal carotid artery in its extracranial course. This ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410040118
更新日期:1978-07-01 00:00:00
abstract::To study distribution and patterns of nerve hypertrophy in chronic inflammatory demyelinating polyneuropathy (CIDP), magnetic resonance neurography with 3-dimensional reconstruction of short tau inversion recovery images was performed in 33 patients. This technique clearly showed longitudinal morphological changes fro...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.24314
更新日期:2015-02-01 00:00:00
abstract:OBJECTIVE:The cortex of patients with cortical dysplasia contains several abnormal cell types. Among the dysplastic cells, cytomegalic neurons are known to be electrically hyperactive and may contribute to epileptic activity. In this study, we sought to identify molecular markers of cytomegalic neurons in focal or hemi...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.20949
更新日期:2006-10-01 00:00:00
abstract:OBJECTIVE:Neonatal white matter injury (NWMI) is a lesion found in preterm infants that can lead to cerebral palsy. Although antagonists of bone morphogenetic protein (BMP) signaling, such as Noggin, promote oligodendrocyte precursor cell (OPC) production after hypoxic-ischemic (HI) injury, the downstream functional ta...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.24907
更新日期:2017-04-01 00:00:00
abstract::Tetrabenazine is considered to act in a manner similar to reserpine to reduce the involuntary movements of tardive dyskinesia or Huntington's disease and to improve psychoses. We determined that tetrabenazine also has properties of a dopamine receptor antagonist by testing the ability of tetrabenazine to block the inh...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410120308
更新日期:1982-09-01 00:00:00
abstract::In multiple sclerosis (MS), the influx of activated T lymphocytes into the brain parenchyma leads to the subsequent damage of oligodendrocytes, the cells that produce central nervous system (CNS) myelin. We report here that interferon beta-1b (IFNbeta-1b), a drug shown to be efficacious in the treatment of patients wi...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410400607
更新日期:1996-12-01 00:00:00
abstract:OBJECTIVE:Somnambulism affects up to 4% of adults and constitutes one of the leading causes of sleep-related violence and self-injury. Diagnosing somnambulism with objective instruments is often difficult because episodes rarely occur in the laboratory. Because sleep deprivation can precipitate sleepwalking, we aimed t...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.21339
更新日期:2008-04-01 00:00:00
abstract::A hereditary ceruloplasmin deficiency associated with severe iron deposition in visceral organ and brain tissues found on histopathological examination at autopsy is discussed. Three siblings of consanguineous Japanese parents were studied. Their clinical symptoms were progressive dementia, extrapyramidal disorders, c...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410370515
更新日期:1995-05-01 00:00:00
abstract::The purpose of this study was to explore the feasibility of obtaining magnetic resonance-measured cerebral metabolic rate of oxygen utilization (MR-CMRO(2)) in acute ischemic stroke patients. Seven stroke patients were serially imaged: 4.5 +/- 0.9 hours (tp1), 3 to 5 days (tp2), and 1 to 3 months (tp3) after symptom o...
journal_title:Annals of neurology
pub_type: 临床试验,杂志文章
doi:10.1002/ana.10433
更新日期:2003-02-01 00:00:00
abstract::Ocular flutter is a rare horizontal eye movement disorder characterized by rapid saccadic oscillations. It has been hypothesized that it is caused by loss of "pause" neuronal inhibition of "burst" neuron function in the paramedian pontine reticular formation (PPRF); however, there have been no imaging studies confirmi...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.1140
更新日期:2001-09-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410190506
更新日期:1986-05-01 00:00:00
abstract:OBJECTIVE:Traumatic brain injury (TBI) often results in traumatic axonal injury (TAI). This can be difficult to identify using conventional imaging. Diffusion tensor imaging (DTI) offers a method of assessing axonal damage in vivo, but has previously mainly been used to investigate groups of patients. Machine learning ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.23824
更新日期:2013-04-01 00:00:00
abstract::The highly encephalitogenic guinea pig peptide 68-88 has been used to develop an effective and reproducible model of protection in the Lewis rat. Doses as low as 0.1 nmol of peptide protected 70% of rats when injected intraperitoneally six and four weeks prior to challenge with 0.05 nmol of the peptide in complete Fre...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410070409
更新日期:1980-04-01 00:00:00
abstract::Selective neuronal vulnerability is a key feature of the neuropathology of Huntington's disease. We used [3H]CP-55,940, a synthetic cannabinoid, to label cannabinoid receptors in tissue sections from individuals dying with Huntington's disease and from normal control subjects. The density of cannabinoid receptors in s...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410360406
更新日期:1994-10-01 00:00:00
abstract::Homocarnosine, a dipeptide of gamma-aminobutyric acid (GABA) and histidine, is thought to be an inhibitory neuromodulator synthesized in subclasses of GABAergic neurons. Homocarnosine is present in human brain in greater amounts (0.4-1.0 micromol/g) than in other animals. The antiepileptic drug vigabatrin increases hu...
journal_title:Annals of neurology
pub_type: 临床试验,杂志文章
doi:10.1002/ana.410440614
更新日期:1998-12-01 00:00:00
abstract:OBJECTIVE:Alterations of the gut microbiome in Parkinson disease (PD) have been repeatedly demonstrated. However, little is known about whether such alterations precede disease onset and how they relate to risk and prodromal markers of PD. We investigated associations of these features with gut microbiome composition. ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.25788
更新日期:2020-08-01 00:00:00
abstract:OBJECTIVE:Chorioamnionitis is associated with increased risk for cerebral palsy (CP) in term infants. A functional polymorphism in the interleukin-6 (IL-6) gene has been implicated in newborn brain injury. We studied whether the IL-6 -174 G/C polymorphism confers increased risk for CP in term infants. METHODS:This pop...
journal_title:Annals of neurology
pub_type: 杂志文章,随机对照试验
doi:10.1002/ana.21766
更新日期:2009-11-01 00:00:00
abstract::Plasma exchange (PE) is the standard treatment in Guillain-Barré syndrome (GBS) patients who have lost the ability to walk. The effect of exchanges before this stage and the optimal number of exchanges for the other patients are still unknown. We randomized 556 GBS patients according to severity and number of exchange...
journal_title:Annals of neurology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1002/ana.410410304
更新日期:1997-03-01 00:00:00
abstract::Averaged electroencephalographic activity related to rhythmic jerking movements was recorded in a patient with a complex neurological symptomatology. The diagnosis of a functional disorder was strongly suggested by his clinical course, inconsistent findings from physical examination, and negative workup. His abnormal ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410200614
更新日期:1986-12-01 00:00:00
abstract::We describe two new clinical syndromes, mirror agnosia and mirror ataxia, both characterized by the deficit of reaching for an object through a mirror in association with a lesion of either parietal lobe. Clinical investigation of 13 patients demonstrated that the impairments affected both sides of the body. In mirror...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/1531-8249(199907)46:1<51::aid-ana9>3.0.co;
更新日期:1999-07-01 00:00:00