Abstract:
:Myelination is a central nervous system (CNS) process wherein oligodendrocyte-axon interactions lead to the establishment of myelin sheaths that stabilize, protect, and electrically insulate axons. In inflammatory demyelinating diseases such as multiple sclerosis (MS), the degeneration and eventual loss of functional myelin sheaths slows and blocks saltatory conduction in axons, which results in clinical impairment. However, remyelination can occur, and lesions can be partially repaired, resulting in clinical remission. The recruitment and activation of resident oligodendrocyte precursor cells (OPCs) play a critical role in the repair process because these cells have the capacity to differentiate into functional myelinating cells. Mature oligodendrocytes, however, are thought to have lost the capacity to develop new myelin sheaths and frequently undergo programmed cell death in MS. The endogenous capacity to generate new oligodendrocytes in MS is limited, and this is predominantly due to the presence of inhibitory components that block OPC differentiation and maturation. Here, we present an overview of recently identified negative regulators of oligodendroglial differentiation and their potential relevance for CNS repair in MS. Because currently available immunomodulatory drugs for MS mainly target inflammatory cascades outside the brain and fail to repair existing lesions, achieving more efficient lesion repair constitutes an important goal for future MS therapies.
journal_name
Ann Neuroljournal_title
Annals of neurologyauthors
Kremer D,Aktas O,Hartung HP,Küry Pdoi
10.1002/ana.22415subject
Has Abstractpub_date
2011-04-01 00:00:00pages
602-18issue
4eissn
0364-5134issn
1531-8249journal_volume
69pub_type
杂志文章,评审abstract:OBJECTIVE:Cognitive decline accompanies acute illness and surgery, especially in the elderly. Surgery engages the innate immune system that launches a systemic inflammatory response that, if unchecked, can cause multiple organ dysfunction. We sought to understand the mechanisms whereby the brain is targeted by the infl...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.22664
更新日期:2011-12-01 00:00:00
abstract::To determine whether the association of the very low density lipoprotein receptor (VLDL-R) gene with Alzheimer's disease (AD), which has recently been identified in Japanese AD patients, is commonly observed in AD patients of other ethnic backgrounds, we have investigated the allele frequency of the polymorphic CGG re...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410400220
更新日期:1996-08-01 00:00:00
abstract::The anatomy of the recently discovered diencephalospinal dopaminergic system is summarized and its possible role in physiological and pathological processes suggested. The cell bodies of origin of this system are localized periventricularly in the dorsal hypothalamus and caudal thalamus, and the terminal innervations ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410140302
更新日期:1983-09-01 00:00:00
abstract:OBJECTIVE:A number of hypotheses have been put forward as to why humans respond to fever by seizing. The current leading hypotheses are that respiratory alkalosis produces an as yet unidentified change in neural excitability or that inflammatory mediators potentiate excitatory synaptic transmission. However, it is well...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.21712
更新日期:2009-08-01 00:00:00
abstract::Gene therapy methods have continued to develop rapidly, and many initial limitations that hampered clinical application have been overcome. Thus serious consideration of clinical application of gene therapy is warranted for selected disorders in which the pathogenesis is well defined. Parkinson's disease has been the ...
journal_title:Annals of neurology
pub_type: 杂志文章,评审
doi:10.1002/ana.10654
更新日期:2003-01-01 00:00:00
abstract::In diabetic nerves, the activation of the polyol pathway and a resulting decrease in Na(+)-K(+) ATPase activity lead to intra-axonal Na(+) accumulation and a smaller Na(+) gradient across the axolemma than normal. To investigate whether glycemic control is associated with acutely reversible changes in axonal excitabil...
journal_title:Annals of neurology
pub_type: 临床试验,杂志文章
doi:10.1002/ana.20232
更新日期:2004-10-01 00:00:00
abstract::An inverse relationship between the cerebrospinal fluid (CSF) opening pressure and the corresponding protein value was found for patients with idiopathic pseudotumor cerebri who underwent their first lumbar puncture (LP) prior to the initiation of therapy. This relationship provides evidence for a pressure-dependent b...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410190116
更新日期:1986-01-01 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::Analysis of mitochondrial DNA (mtDNA) in muscle and blood from 72 patients with mitochondrial myopathy showed that 30 had major deletions of a variable proportion of muscle mtDNA. All of these 30 patients presented with progressive external ophthalmoplegia and limb weakness, and 8 had the additional features of the Ke...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410260603
更新日期:1989-12-01 00:00:00
abstract::Regional cerebral blood flow (rCBF) was measured in human subjects during saccadic eye movements by a 254-channel dynamic gamma camera. Focal rCBF increases were repeatedly observed in an area within the middle precentral and premotor regions which corresponds to the frontal eye field in humans. Our findings suggest t...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410050112
更新日期:1979-01-01 00:00:00
abstract::Membrane cofactor protein (CD46) is a member of a family of glycoproteins that are regulators of complement and prevent activation of complement on autologous cells. Recently, CD46 has been identified as the cellular receptor for human herpesvirus Type 6 (HHV-6). Elevated levels of soluble CD46 have been described in ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.1135
更新日期:2001-10-01 00:00:00
abstract::Analysis of the pathophysiology of hypokalemic paralysis, as it occurs in barium poisoning, chronic potassium deficiency, and thyrotoxicosis, suggests that these disorders may have a similar mechanism. An increased ratio of muscle sodium permeability to potassium permeability reduces the ionic diffusion potential, whi...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410110602
更新日期:1982-06-01 00:00:00
abstract::Benign familial neonatal convulsions (BFNC) is a rare dominantly inherited epileptic syndrome characterized by frequent brief seizures within the first days of life. The disease is caused by mutations in one of two recently identified voltage-gated potassium channel genes, KCNQ2 or KCNQ3. Here, we describe a four-gene...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/1531-8249(199909)46:3<305::aid-ana5>3.0.co
更新日期:1999-09-01 00:00:00
abstract::Neurosurgical procedures such as the dorsal root entry zone operation, ganglionectomy, and spinal-cord stimulation have been offered to patients with intractable post-herpetic neuralgia (PHN). Poor efficacy or high morbidity have limited the overall usefulness of these procedures. We recently conducted a preliminary o...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410350716
更新日期:1994-01-01 00:00:00
abstract::A patient with generalized convulsions noted that seizures were reliably precipitated by mental arithmetic. The interictal electroencephalogram revealed only a mild, diffuse, nonspecific disturbance, but bursts of generalized epileptiform activity with no obvious clinical expression accompanied efforts at mental arith...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410110609
更新日期:1982-06-01 00:00:00
abstract::Benzodiazepines can regulate neoplastic growth and immune response through specific peripheral benzodiazepine receptors. We investigated the presence of peripheral and classic central benzodiazepine receptors as well as diazepam-binding inhibitor, an endogenous ligand of both types of receptors, in different human cer...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410260411
更新日期:1989-10-01 00:00:00
abstract::Various C-terminally truncated amyloid beta peptides (Abeta) are linked to Alzheimer's disease (AD) pathogenesis. Cerebrospinal fluid (CSF) concentrations of Abeta38, Abeta40, and Abeta42 were measured by enzyme-linked immunosorbent assay in 30 patients with AD and 26 control subjects. CSF Abeta42 levels was decreased...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.20508
更新日期:2005-07-01 00:00:00
abstract::Between 36 and 44 weeks after conception, telencephalic white matter in the newborn appears to be particularly vulnerable to insults that result in morphological disturbances. Available evidence indicates that this disorder (or group of disorders), named acquired perinatal leukoencephalopathy, reflects a decrease in b...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410160102
更新日期:1984-07-01 00:00:00
abstract:OBJECTIVE:Migraine is among the most common and debilitating neurological conditions. Familial hemiplegic migraine type 1 (FHM1), a monogenic migraine subtype, is caused by gain-of-function of voltage-gated CaV 2.1 calcium channels. FHM1 mice carry human pathogenic mutations in the α1A subunit of CaV 2.1 channels and a...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.24449
更新日期:2015-08-01 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::Intellectual disability is common and is associated with significant morbidity. Until the latter half of the 20th century, there were no efficacious treatments. Following initial breakthroughs associated with newborn screening and metabolic corrections, little progress was made until recently. With improved understand...
journal_title:Annals of neurology
pub_type: 杂志文章,评审
doi:10.1002/ana.24002
更新日期:2013-09-01 00:00:00
abstract::We studied rhesus monkeys with hemiparkinsonism or bilateral parkinsonism produced by unilateral or bilateral intracarotid administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Using a standardized clinical rating scale, 4 hemiparkinsonian monkeys showed a 13 to 56% (mean, 36%) spontaneous improvement during...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410290618
更新日期:1991-06-01 00:00:00
abstract::Two brothers with profound neonatal hypotonia and hyporeflexia and electrodiagnostic testing consistent with lower motor neuron pathology were found to have a leukodystrophy. Using single-strand conformational polymorphism analysis and direct sequencing, a mutation within exon 3 of the gene encoding proteolipid protei...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410360618
更新日期:1994-12-01 00:00:00
abstract::The frequency with which patients presenting with acute or chronic noncompressive cord syndromes subsequently develop multiple sclerosis is uncertain. Magnetic resonance imaging (MRI) was performed on 121 patients with such syndromes to determine the frequency of asymptomatic brain lesions and to assess the sensitivit...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410220607
更新日期:1987-12-01 00:00:00
abstract:OBJECTIVE:Limited evidence is available to guide treatment of depression for persons with epilepsy. We evaluated the comparative effectiveness of sertraline and cognitive behavior therapy (CBT) for depression, quality of life, seizures, and adverse treatment effects. METHODS:We randomly assigned 140 adult outpatients ...
journal_title:Annals of neurology
pub_type: 杂志文章,随机对照试验
doi:10.1002/ana.25561
更新日期:2019-10-01 00:00:00
abstract:OBJECTIVE:Infantile spasms are seizures associated with a severe epileptic encephalopathy presenting in the first 2 years of life, and optimal treatment continues to be debated. This study evaluates early and sustained response to initial treatments and addresses both clinical remission and electrographic resolution of...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.24594
更新日期:2016-03-01 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::Central motor conduction times for the adductor pollicis muscle, the twitch force of that muscle to scalp magnetic motor cortex stimulation, and the maximum force of phasic voluntary contraction of the same muscle were measured in 15 patients with multiple sclerosis. Two tests of manual dexterity of the same hand also...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410290104
更新日期:1991-01-01 00:00:00
abstract::The fate of neurofilament (NF) proteins was examined in sections of nerves from rats that survived for 3 to 90 days following nerve transection, using anti-NF monoclonal antibodies and immunohistochemical techniques. The same methods were also applied to twenty-three human nerve biopsy specimens. Granular debris with ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410160312
更新日期:1984-09-01 00:00:00
abstract::Plasma valproate concentrations were monitored prospectively in 54 previously untreated adult patients with epilepsy. Dose and plasma concentration were highly correlated. Adverse effects were common in association with plasma levels above 100 micrograms/ml. In patients suffering tonic-clonic seizures without focal sy...
journal_title:Annals of neurology
pub_type: 临床试验,杂志文章
doi:10.1002/ana.410140107
更新日期:1983-07-01 00:00:00