Abstract：
:Downbeat nystagmus (DBN) is the most frequent form of acquired persisting fixation nystagmus. It is hypothesized to occur when physiological inhibitory cerebellar input, namely of the flocculus, to the vestibular nuclei is inhibited. The second most frequent form of acquired nystagmus is upbeat nystagmus (UBN). UBN is probably caused by an imbalance of vertical vestibulo-ocular reflex tone. GABA-ergic substances like baclofen have been used to treat DBN and UBN, but they have had only moderate success. Animal experiments have shown that aminopyridines [3,4-diaminopyridine (3,4-DAP) and 4-aminopyridine (4-AP)], nonselective blockers of the Kv family of voltage-gated potassium channels, increase Purkinje-cell (PC) excitability. It was assumed that such enhancement of PC activity could restore to normal levels the inhibitory influence of the cerebellar cortex on vertical eye movements. On the basis of these assumptions, we evaluated the efficacy and underlying mechanisms of aminopyridines in DBN and UBN as well as in another cerebellar disorder with an impaired PC function: episodic ataxia type 2 (EA2), which is caused by mutations of the PQ-calcium channel. In a placebo-controlled trial on 17 patients we demonstrated that 3,4-DAP significantly reduces the intensity of DBN. This was confirmed in a recent study with 4-AP, which also showed that 4-AP restores gaze-holding ability independently of fixation in DBN. The efficacy of 4-AP in UBN was demonstrated in single patients. Finally, in an open trial on three patients with EA2 we showed that 4-AP prevents attacks of ataxia. This was also found in an animal model (the tottering mouse) of EA2. The clinical efficacy of 4-AP in EA2 is being further evaluated in an ongoing randomized controlled crossover trial. In conclusion, the use of aminopyridines in DBN, UBN, and EA2 is a new treatment principle for vestibular, cerebellar, and ocular motor disorders.
journal_name
Prog Brain Resjournal_title
Progress in brain researchauthors
Strupp M,Kalla R,Glasauer S,Wagner J,Hüfner K,Jahn K,Brandt Tdoi
10.1016/S0079-6123(08)00676-6subject
Has Abstractpub_date
2008-01-01 00:00:00pages
535-41eissn
0079-6123issn
1875-7855pii
S0079-6123(08)00676-6journal_volume
171pub_type
杂志文章abstract：:Nitric oxide (NO) is widespread in the nervous system and is thought to play a role in a variety of different neuronal functions, including learning and memory (see other chapters, this volume). A number of behavioral studies have indicated that NO is involved in several types of learning such as motor learning (Yanag...
journal_title：Progress in brain research
pub_type： 杂志文章,评审
doi：10.1016/s0079-6123(08)63206-9
更新日期：1998-01-01 00:00:00
abstract：:The nervous system can generate rhythms of various frequencies; on the low-frequency side, we have the circuits regulating circadian rhythms with a 24-h period, while on the high-frequency side we have the motor circuits that underlie flight in a hummingbird. Given the ubiquitous nature of rhythms, it is surprising th...
journal_title：Progress in brain research
pub_type： 杂志文章,评审
doi：10.1016/B978-0-444-53613-6.00004-6
更新日期：2010-01-01 00:00:00
abstract：:Sex hormone effects on hypothalamic neurons have been worked out to a point where receptor mechanisms are relatively well understood, a neural circuit for a sex steroid-dependent behavior has been determined, and several functional genomic regulations have been discovered and conceptualized. With that knowledge in han...
journal_title：Progress in brain research
pub_type： 杂志文章,评审
doi：10.1016/S0079-6123(06)58012-4
更新日期：2006-01-01 00:00:00
abstract：:Nerve growth factor (NGF) is required for the survival of developing sympathetic and sensory neurons. In the absence of NGF, these neurons undergo protein synthesis-dependent apoptosis. Ten years have gone by since the first reports of specific genes being upregulated during NGF deprivation-induced cell death. Over th...
journal_title：Progress in brain research
pub_type： 历史文章,杂志文章,评审
doi：10.1016/S0079-6123(03)46008-1
更新日期：2004-01-01 00:00:00
abstract：:Objects have specific cognitive attributes, elicit particular visuo-motor responses, and require visual processes beyond primary visual cortex to combine information over extended regions as a basis for the segmentation and integration of visual objects. As well as segmentation, the assignment of region boundaries to ...
journal_title：Progress in brain research
pub_type： 杂志文章,评审
doi：10.1016/S0079-6123(07)64008-4
更新日期：2007-01-01 00:00:00
abstract：:Activated microglia release a number of substances, the specific cocktail released depending on the stimulus. Many of the substances released by microglia also serve to activate them, suggesting the presence of a number of autocrine/paracrine loops. Because of the low density of microglia present in the normal brain, ...
journal_title：Progress in brain research
pub_type： 杂志文章,评审
doi：10.1016/S0079-6123(01)32103-9
更新日期：2001-01-01 00:00:00
abstract：:It has been known for decades that females are more susceptible than men to inflammatory autoimmune diseases, including multiple sclerosis (MS), rheumatoid arthritis, and psoriasis. In addition, female patients with these diseases experience clinical improvements during pregnancy with a temporary "rebound" exacerbatio...
journal_title：Progress in brain research
pub_type： 杂志文章,评审
doi：10.1016/S0079-6123(09)17516-7
更新日期：2009-01-01 00:00:00
abstract：:Glaucoma is an age-related neurodegenerative disease that begins at the onset of aging. In this disease, there is an involvement of the immune system and therefore of the microglia. The purpose of this study is to evaluate the microglial activation using a mouse model of ocular hypertension (OHT) at the onset of aging...
journal_title：Progress in brain research
pub_type： 杂志文章
doi：10.1016/bs.pbr.2020.05.024
更新日期：2020-01-01 00:00:00
abstract：:In the kidney, the actions of the antidiuretic hormone arginine vasopressin (AVP) renders the collecting duct highly permeable to water. This large increase in water permeability is largely due to the translocation of the water channel aquaporin-2 (AQP-2) from intracellular storage vesicles to the apical plasma membra...
journal_title：Progress in brain research
pub_type： 杂志文章,评审
doi：10.1016/S0079-6123(08)00444-5
更新日期：2008-01-01 00:00:00
abstract：:It has been tacitly assumed that a long descending motor tract axon consists of a private line connecting the cell of origin to a single muscle, as a motoneuron innervates a single muscle. However, this notion of a long descending motor tract referred to as a private line is no longer tenable, since recent studies hav...
journal_title：Progress in brain research
pub_type： 杂志文章
doi：10.1016/S0079-6123(05)51017-3
更新日期：2006-01-01 00:00:00
abstract：:The organization of key molecules at glutamatergic synapses in the rat cerebellar cortex as analyzed by high resolution immunocytochemical techniques using gold particles as markers. The distinct compartmentation of glutamate and glutamine was consistent with biochemical data indicating an active role of glia in the r...
journal_title：Progress in brain research
pub_type： 杂志文章,评审
doi：10.1016/s0079-6123(08)63360-9
更新日期：1997-01-01 00:00:00
abstract：:Local recurrent connections endow the cerebellar cortex with an intrinsic dynamics. We performed computer simulations to predict the frequency bands of the oscillations that will most likely emerge. Feedback inhibition from the Golgi to the granule cells induced 10-50 Hz oscillations, the period at resonance being app...
journal_title：Progress in brain research
pub_type： 杂志文章,评审
doi：10.1016/S0079-6123(04)48015-7
更新日期：2005-01-01 00:00:00
abstract：:A computational model of the mammalian spinal cord circuitry incorporating a two-level central pattern generator (CPG) with separate half-center rhythm generator (RG) and pattern formation (PF) networks is reviewed. The model consists of interacting populations of interneurons and motoneurons described in the Hodgkin-...
journal_title：Progress in brain research
pub_type： 杂志文章,评审
doi：10.1016/S0079-6123(06)65015-2
更新日期：2007-01-01 00:00:00
abstract：:Alzheimer's disease (AD), the most common type of adult-onset dementia, is characterized by a variety of brain abnormalities, including degeneration of certain populations of nerve cells, alterations in the neuronal cytoskeleton, and the abnormal deposition of amyloid within brain parenchyma. Pathogenetic processes th...
journal_title：Progress in brain research
pub_type： 杂志文章,评审
doi：10.1016/s0079-6123(08)63186-6
更新日期：1990-01-01 00:00:00
abstract：:The aim of this experiment was to investigate whether there were differences in decision-making skills between different age groups (Under 16, 18 and 23) of elite academy footballers on a video-based task of real-life football scenarios. It also explored the relationship between individual performance on the task and ...
journal_title：Progress in brain research
pub_type： 杂志文章
doi：10.1016/bs.pbr.2020.06.015
更新日期：2020-01-01 00:00:00
abstract：:Essential infantile esotropia (EIE) is often attributed to a primary disturbance within the visual cortex based upon the findings of monocular horizontal optokinetic asymmetry and correlative horizontal motion detection asymmetry. However, these physiologic aberrations conform to what would be observed if the visual c...
journal_title：Progress in brain research
pub_type： 杂志文章
doi：10.1016/bs.pbr.2019.04.001
更新日期：2019-01-01 00:00:00
abstract：:Recent accounts of tinnitus development and maintenance assign an important role to central mechanisms. Residual inhibition is a frequent phenomenon in individuals with tinnitus, and refers to the fact that tinnitus can temporarily be reduced by presenting sounds or noises that inhibit tinnitus for a limited time even...
journal_title：Progress in brain research
pub_type： 杂志文章,评审
doi：10.1016/S0079-6123(07)66044-0
更新日期：2007-01-01 00:00:00
abstract：:Motor control of different segments of the body with multiple degrees of freedom appears to be coordinated by utilizing preferred axes of motor activity. This hypothesis may also be applied to vestibular control of posture. To explore this question we studied the anatomical relationship between the head and the cervic...
journal_title：Progress in brain research
pub_type： 杂志文章
doi：10.1016/s0079-6123(08)62282-7
更新日期：1993-01-01 00:00:00
abstract：:Recent years have brought a rapid growth in knowledge of the prodromal phase of Parkinson's disease (PD). It is now clear that the clinical phase of PD is preceded by a phase of progressing neurodegeneration lasting many years. This involves not only central nervous system structures outside the substantia nigra and n...
journal_title：Progress in brain research
pub_type： 杂志文章,评审
doi：10.1016/bs.pbr.2020.01.003
更新日期：2020-01-01 00:00:00
abstract：:Schwann cells (SCs), when implanted in the injured spinal cord, support regeneration of axons, myelinate or ensheathe regenerated axons in a normal way, reduce cyst formation in the injured tissue, reduce secondary damage of tissue around the initial injury site, and modestly improve limb movements. If SC transplantat...
journal_title：Progress in brain research
pub_type： 杂志文章,评审
doi：10.1016/B978-0-444-59544-7.00014-7
更新日期：2012-01-01 00:00:00
abstract：:Although visually responsive neurons predominate in the deep layers of the superior colliculus (SC), the majority of them also receive sensory inputs from nonvisual sources (i.e. auditory and/or somatosensory). Most of these 'multisensory' neurons are able to synthesize their cross-modal inputs and, as a consequence, ...
journal_title：Progress in brain research
pub_type： 杂志文章,评审
doi：10.1016/s0079-6123(01)34011-6
更新日期：2001-01-01 00:00:00
abstract：:Noradrenergic LC neurons appear to be relatively unique in the brain, being unsurpassed in the divergence and ubiquity of their projections through the central nervous system. In this regard, they share certain characteristics with peripheral noradrenaline neurons of the sympathetic nervous system. As such they would ...
journal_title：Progress in brain research
pub_type： 杂志文章,评审
doi：10.1016/s0079-6123(08)63797-8
更新日期：1991-01-01 00:00:00
abstract：:Nicotinic acetylcholine receptors (nAChRs) are widely distributed in the central nervous system and have been implicated in multiple behavioral paradigms and pathological conditions. Nicotinic therapeutic interventions require an extensive characterization of native nAChRs including mapping of their distribution and f...
journal_title：Progress in brain research
pub_type： 杂志文章,评审
doi：10.1016/S0079-6123(03)45007-3
更新日期：2004-01-01 00:00:00
abstract：:The cellular and ionic mechanisms that generate the rhythm in central pattern generator (CPG) networks for simple movements are not well understood. Using vertebrate locomotion, respiration and mastication as exemplars, I describe four main principles of rhythmogenesis: (1) rhythmogenic ionic currents underlie all CPG...
journal_title：Progress in brain research
pub_type： 杂志文章
doi：10.1016/B978-0-444-53613-6.00014-9
更新日期：2010-01-01 00:00:00
abstract：:Over the past three decades, developmental neurobiologists have made tremendous progress in defining basic principles of brain development. This work has changed the way we think about how brains develop. Thirty years ago, the dominant model was strongly deterministic. The relationship between brain and behavioral dev...
journal_title：Progress in brain research
pub_type： 杂志文章,评审
doi：10.1016/B978-0-444-53884-0.00015-4
更新日期：2011-01-01 00:00:00
abstract：:Primates are able to recognize a particular object despite major differences in the retinal images of the object. Inferior temporal cortex is suggested to be involved in this invariant object recognition. Neurons of this cortex show shape selectivity and it has been shown that this shape selectivity is relatively inva...
journal_title：Progress in brain research
pub_type： 杂志文章
doi：10.1016/s0079-6123(08)63330-0
更新日期：1996-01-01 00:00:00
abstract：:The dorsal striatum (caudate putamen) contains two types of GABAergic medium spiny neurons (MSNs) that are distinguished by the expression of either the opioid peptide, enkephalin, or the opioid peptide, dynorphin, as well as the tachykinin substance P. Pharmacological studies suggest that these peptides modulate loca...
journal_title：Progress in brain research
pub_type： 杂志文章,评审
doi：10.1016/S0079-6123(06)60016-2
更新日期：2007-01-01 00:00:00
abstract：:The study of consciousness within cognitive neuroscience has been dominated in recent years by investigations originating from collaborations between neuroscientific investigators and Buddhist meditation practitioners. The results have been remarkable, particularly when quantitative and qualitative research methods ha...
journal_title：Progress in brain research
pub_type： 杂志文章,评审
doi：10.1016/bs.pbr.2018.10.016
更新日期：2019-01-01 00:00:00
abstract：:The capacity to sustain high-intensity aerobic exercise is essential for endurance performance. Therefore, it is important to understand what is the factor limiting time to exhaustion (TTE) in healthy and fit adults. In Study 1, maximal voluntary cycling power (MVCP) was measured in 11 volunteers before and immediatel...
journal_title：Progress in brain research
pub_type： 杂志文章
doi：10.1016/bs.pbr.2018.09.012
更新日期：2018-01-01 00:00:00
abstract：:Disrupted in Schizophrenia-1 (DISC1) is one of the most likely susceptibility genes for schizophrenia (SZ). DISC1 is being established as a hub protein with various functions in the pre- and postnatal development of the nervous system. Since generation of a knockout (KO) mouse has proved challenging, various alternati...
journal_title：Progress in brain research
pub_type： 杂志文章,评审
doi：10.1016/S0079-6123(09)17909-8
更新日期：2009-01-01 00:00:00
