Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028738 (nystagmus)
 7,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eye movements of four macaque monkeys were investigated after unilateral micro-injections of the GABA agonist muscimol (1 microgram in 1 microliter NaCl) into the caudal fastigial nucleus, i.e. the fastigial oculomotor region. Spontaneous eye movements in the dark and in the light were tested, as well as those evoked by vestibular stimulation in the dark (sinusoidal: 0.1-0.2 Hz, +/- 40-100 deg/s, velocity trapezoid acceleration 40 deg/s2, constant velocity 120 deg/s), optokinetic stimulation (sinusoidal: 0.1-0.2 Hz, +/- 40-100 deg/s, constant velocity 60-100 deg/s), and visual-vestibular conflict stimulation. With these stimuli, smooth pursuit mechanisms (fast build-up of optokinetic slow phase velocity), the vestibulo-ocular reflex (VOR) and the velocity storage mechanism were investigated. Muscimol injections consistently led to specific eye movement changes which were maximal 30-60 min after the injection and lasted 4-6 h. The fast initial rise of OKN slow phase velocity to the contralateral side decreased by 45% (range 24%-82%) of its pre-injection value, while it was virtually unaltered on the ipsilateral side (average decrease of 1%, range from a decrease of 20% to an increase of 32%). For conflict ramp stimulation, the suppression of vestibular nystagmus was less (decrease of 50%, range 12-82%) towards the contralateral side while it remained unchanged on the ipsilateral side. The VOR in the dark and the velocity storage mechanism were not altered. For the latter, the slow build-up of optokinetic nystagmus velocity, the optokinetic afternystagmus (OKAN) and the time constant of decay for the vestibular nystagmus were evaluated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of muscimol micro-injections into the fastigial nucleus on the optokinetic response and the vestibulo-ocular reflex in the alert monkey. 835 41

In the mammalian labyrinth, GABAA receptor subtypes are involved in the excitatory neurotransmission between the vestibular type II hair cells and the afferent neurons. Additional afferent ionophoric receptor channels, sensitive to further transmitter candidates, are discussed for both types I and II hair cells. GABA accelerates excitotoxic cell death in cortical neurons. This GABA-ergic neurotoxic action forms an appropriate pathophysiological model explaining peripheral labyrinthine disorders characterized by the spontaneous labyrinthine nystagmus and vertigo in man. A calculated GABAA receptor antagonism was envisaged in order to attenuate the pathological vestibular imbalance following one-sided GABA-accelerated vestibular neurotoxicity. Moderate allosteric blockers of the GABAA receptor channel and weak inverse agonists of the benzodiazepine binding site meet some requirements for potentially successful clinical application. The suppressing action of the suitable drugs picrotoxin and flumazenil on labyrinthine nystagmus and vertigo, tested in clinical trials, supports the hypothesis that GABAA receptors are involved in vestibular neurotransmission, even in humans. The test results promise the development of a successful vestibular receptorpharmacology in the near future.
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PMID:Receptorpharmacological models for the therapy of labyrinthine vertigo. 872 11

The horizontal vestibulo-ocular reflex was studied in pigmented rats, which had been unilaterally, chemically labyrinthectomised 6-144 days previously. During this partially compensated stage after unilateral labyrinthectomy (UL), both static and dynamic deficits remain. The former was evaluated by recording of spontaneous eye movements in darkness, and the latter by estimating the slow-phase velocity (SPV) gain of compensatory eye movements during horizontal vestibular stimulation. The GABA(B) agonist baclofen caused a reversal of the remaining ipsilesional drift of the eyes in darkness into a nystagmus with a contralesional slow phase. The GABA(B) antagonist CGP 36742 caused a decompensation by exaggerating the remaining ipsilesional eye drift. Further, baclofen equilibrated or reversed the asymmetry between ipsi- and contralesional SPV gains during horizontal sinusoidal rotations at 0.2 Hz and 0.8 Hz. This was achieved by an increase in the ipsilesional gain and a decrease in the contralesional gain. The phase lead during sinusoidal rotation (0.2 Hz) was larger following rotation to the lesioned side than to the intact side in UL rats. This asymmetry was reversed by baclofen. CGP 36742 inhibited the effects of baclofen, while the antagonist per se aggravated SPV gain and phase lead asymmetries in UL rats during vestibular stimulation. Per- and post-rotatory nystagmus induced by velocity step stimulation revealed an imperfect velocity-storage function in UL animals, which was modulated by baclofen. An investigation of the baclofen effect on SPV gain asymmetry during different time intervals after chemical UL showed a completely developed effect on the 6th day. Bilateral flocculectomy did not alter the effects of baclofen on UL animals. It is concluded that physiological stimulation of GABA(B) receptors contributes to minimise the vestibulo-oculomotor asymmetry during the partially compensated period after UL. Administration of an agonist or an antagonist changes the asymmetry towards the ipsi- or contralesional side, possibly by altering the spontaneous neuronal activity in the bilateral medial vestibular nuclei. The results are compatible with a hypothesis, supported by in vitro slice experiments, that the efficacy of GABA(B) receptors is up-regulated on the ipsilesional side and down-regulated on the contralesional side.
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PMID:GABA(B) receptors contribute to vestibular compensation after unilateral labyrinthectomy in pigmented rats. 1102 23

Acquired nystagmus occurs frequently in patients with multiple sclerosis and is often the cause of illusory motion of the environment (oscillopsia), and blurring of vision. Based primarily on the beneficial effect of gabapentin on acquired pendular nystagmus (APN), a GABAergic mechanism in controlling nystagmus has been hypothesised. If increasing GABA concentrations in the CNS are critical for the treatment of nystagmus, then a selective GABAergic drug should be highly successful. However, as gabapentin is not a selective GABAergic agent, vigabatrin, a "pure" GABAergic medication, and gabapentin, were compared in a single blind cross over trial in eight patients with definite multiple sclerosis. Patients were randomly assigned to begin with gabapentin (1200 mg daily) or vigabatrin (2000 mg daily). Neuro-ophthalmological and electro-oculographic (EOG) evaluations were performed four and three times, respectively. Treatment efficacy was based on improving visual acuity and EOG indices (amplitude or frequency of nystagmus, or both) by at least 50% of pretreatment values. Three out of eight patients dropped out due to adverse effects. In the remaining five patients gabapentin improved symptomatic pendular or gaze evoked jerk nystagmus in four. Three patients decided to continue gabapentin therapy. Importantly, vigabatrin proved useful in only one out of five patients, suggesting that gabapentin effectiveness may be related to additional non-GABAergic mechanisms of action. Interaction with cerebral glutamate transmission by inhibition of NMDA receptor might be an alternative hypothesis for the therapeutic action of gabapentin.
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PMID:Gabapentin but not vigabatrin is effective in the treatment of acquired nystagmus in multiple sclerosis: How valid is the GABAergic hypothesis? 1141 74

We studied the role of the pretectal nucleus of the optic tract (NOT) in the development of monocular optokinetic nystagmus (OKN) asymmetries and latent nystagmus (LN) in two monkeys reared with binocular deprivation (BD) caused by binocular eyelid suture for either the first 25 or 55 days of life. Single-unit recordings were performed in the right and left NOT of both monkeys at 2-3 yr of age and compared with similar unit recordings in normally reared monkeys. We also examined ocular motor behavior during electrical stimulation of the NOT and during pharmacological inactivation and activation using GABA(A) agonists and antagonists. In BD animals a large proportion of NOT units was dominated by the contralateral eye, in striking contrast to normal animals where 100% of NOT units were sensitive to stimuli delivered to either eye. In the 55-day BD animal no binocularly sensitive neurons were found, while in the 25-day BD animal 60% of NOT units retained at least some binocular sensitivity. Differences in direction sensitivity were also observed in BD animals. We found that 56% of units in the 55-day BD monkey and 10% of units in the 25-day BD monkey responded preferentially to contraversive visual motion. In contrast, only 5% of the NOT units encountered in normally reared monkeys respond preferentially during contraversive visual motion, the rest were most sensitive to ipsiversive visual motion. NOT neurons of BD monkeys showed a wide range of speed sensitivities similar to that of normal monkeys. Unilateral electrical stimulation of the NOT in BD animals induced a conjugate nystagmus with slow phases directed toward the side of stimulation. When we blocked the activity of NOT units with muscimol, a potent GABA(A) agonist, LN was abolished. In contrast, LN was increased when spontaneous activity of the NOT was enhanced with bicuculline, a GABA(A) antagonist. Our results indicate that the NOT in BD monkeys plays an important role in the OKN deficits and LN generation during monocular viewing. We hypothesize that the large proportion of units dominated by the contralateral eye contribute to the development of monocular OKN asymmetries and LN.
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PMID:Gaze-stabilizing deficits and latent nystagmus in monkeys with early-onset visual deprivation: role of the pretectal not. 1149 41

Gamma-aminobutyric acid (GABA) is the most prevalent inhibitory neurotransmitter in the vertebrate brain. It can exert its influence either as GABAergic projection pathways or as local interneurons, which play an essential role in many visual functions. However, no GABAergic visual pathways have been studied in frogs so far. In the present study, GABAergic pathways in the central visual system of Rana pipiens were investigated with double-labeling techniques, combining immunocytochemistry for GABA with Rhodamine microspheres for retrograde tracing. Three GABAergic visual pathways were identified: (1) a retino-tectal projection, from retina to the contralateral optic tectum (OT); (2) an ipsilateral projection from the nucleus of the basal optic root (nBOR) to the pretectal nucleus lentiformis mesencephali (nLM); and (3) a second-order pathway from the nucleus isthmi (NI), bilaterally, to the optic tectum. These results indicate that GABA is involved in both first-order (retina to optic tectum) as well as second-order (nucleus isthmi to optic tectum) visual projections in Rana pipiens, and may play a major role in mediating visuomotor reflexs such as optokinetic nystagmus or other visually guided behaviors.
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PMID:GABAergic visual pathways in the frog Rana pipiens. 1149 22

Neuropathic pain, whether of peripheral or central origin, is characterized by a neuronal hyperexcitability in damaged areas of the nervous system. In peripheral neuropathic pain, damaged nerve endings exhibit abnormal spontaneous and increased evoked activity, partly due to an increased and novel expression of sodium channels. In central pain, although not explored in detail, the spontaneous pain and evoked allodynia are also best explained by a neuronal hyperexcitability. The peripheral hyperexcitability is due to a series of molecular changes at the level of the peripheral nociceptor, in dorsal root ganglia, in the dorsal horn of the spinal cord, and in the brain. These changes include abnormal expression of sodium channels, increased activity at glutamate receptor sites, changes in gamma-aminobutyric acid (GABA-ergic) inhibition, and an alteration of calcium influx into cells. The neuronal hyperexcitability and corresponding molecular changes in neuropathic pain have many features in common with the cellular changes in certain forms of epilepsy. This has led to the use of anticonvulsant drugs for the treatment of neuropathic pain. Carbamazepine and phenytoin were the first anticonvulsants to be used in controlled clinical trials. Studies have shown these agents to relieve painful diabetic neuropathy and paroxysmal attacks in trigeminal neuralgia. Subsequent studies have shown the anticonvulsant gabapentin to be effective in painful diabetic neuropathy, mixed neuropathies, and postherpetic neuralgia. Lamotrigine, a new anticonvulsant, is effective in trigeminal neuralgia, painful peripheral neuropathy, and post-stroke pain. Other anticonvulsants, both new and old, are currently undergoing controlled clinical testing. The most common adverse effects of anticonvulsants are sedation and cerebellar symptoms (nystagmus, tremor and incoordination). Less common side-effects include haematological changes and cardiac arrhythmia with phenytoin and carbamazepine. The introduction of a mechanism-based classification of neuropathic pain, together with new anticonvulsants with a more specific pharmacological action, may lead to more rational treatment for the individual patient with neuropathic pain.
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PMID:Anticonvulsants in neuropathic pain: rationale and clinical evidence. 1188 43

The horizontal vestibulo-oculomotor reflex was studied in pigmented rats during the first 5 days after a unilateral chemical or surgical vestibular deafferentation. Spontaneous eye movements in darkness and slow phase velocity gain of compensatory eye movements during horizontal sinusoidal rotation were evaluated. The most evident vestibulo-oculomotor symptom immediately after a unilateral vestibular loss was a spontaneous nystagmus, which gradually abated during the following days. Further, an asymmetry between ipsi- and contra-lesional gains was evident during sinusoidal vestibular stimulation. Single systemic doses of the GABA(B) receptor antagonist [3-[1-(S)-[[3-(cyclohexylmethyl)-hydroxyphosphinoyl]-2-(S)-hydroxypropyl]amino]ethyl]-benzoic acid (CGP 56433A), the agonist baclofen, or the GABA(A) receptor agonist (4,5,6,7-tetrahydroisoxazolo-[5,4-c]-pyridin-3-ol (THIP) were given at different intervals after unilateral vestibular deafferentation. CGP 56433A highly aggravated the vestibulo-oculomotor symptoms, observed as an increase in spontaneous nystagmus and slow phase velocity gain asymmetry. This effect was most pronounced during the first 2 days after unilateral vestibular loss, when CGP 56433A even decompensated the vestibular system to the extent that all vestibular responses were abolished. Baclofen caused no effect during the first days after unilateral vestibular loss, but in parallel with the abatement of spontaneous nystagmus, the drug equilibrated or even reversed the remaining spontaneous nystagmus with corresponding effects on the slow-phase velocity gain asymmetry. The effects of baclofen were very similar after both chemical and surgical deafferentation. THIP caused a slight depression of all vestibular responses. All single dose effects of the drugs were transient. Altogether these results reveal that endogenous stimulation of GABA(B) receptors in GABA-ergic vestibulo-oculomotor circuits are important for reducing the vestibular asymmetry during the early period after unilateral vestibular deafferentation. A possible role for GABA(B) receptors in the reciprocal inhibitory commissural pathways in the vestibular nuclei is suggested.
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PMID:Early compensation of vestibulo-oculomotor symptoms after unilateral vestibular loss in rats is related to GABA(B) receptor function. 1203 49

Nystagmus induced by off-vertical axis rotation (OVAR) about a head yaw axis is composed of a yaw bias velocity and modulations in eye position and velocity as the head changes orientation relative to gravity. The bias velocity is dependent on the tilt of the rotational axis relative to gravity and angular head velocity. For axis tilts <15 degrees, bias velocities increased monotonically with increases in the magnitude of the projected gravity vector onto the horizontal plane of the head. For tilts of 15-90 degrees, bias velocity was independent of tilt angle, increasing linearly as a function of head velocity with gains of 0.7-0.8, up to the saturation level of velocity storage. Asymmetries in OVAR bias velocity and asymmetries in the dominant time constant of the angular vestibuloocular reflex (aVOR) covaried and both were reduced by administration of baclofen, a GABA(B) agonist. Modulations in pitch and roll eye positions were in phase with nose-down and side-down head positions, respectively. Changes in roll eye position were produced mainly by slow movements, whereas vertical eye position changes were characterized by slow eye movements and saccades. Oscillations in vertical and roll eye velocities led their respective position changes by approximately 90 degrees, close to an ideal differentiation, suggesting that these modulations were due to activation of the orienting component of the linear vestibuloocular reflex (lVOR). The beating field of the horizontal nystagmus shifted the eyes 6.3 degrees /g toward gravity in side down position, similar to the deviations observed during static roll tilt (7.0 degrees /g). This demonstrates that the eyes also orient to gravity in yaw. Phases of horizontal eye velocity clustered ~180 degrees relative to the modulation in beating field and were not simply differentiations of changes in eye position. Contributions of orientating and compensatory components of the lVOR to the modulation of eye position and velocity were modeled using three components: a novel direct otolith-oculomotor orientation, orientation-based velocity modulation, and changes in velocity storage time constants with head position re gravity. Time constants were obtained from optokinetic after-nystagmus, a direct representation of velocity storage. When the orienting lVOR was combined with models of the compensatory lVOR and velocity estimator from sequential otolith activation to generate the bias component, the model accurately predicted eye position and velocity in three dimensions. These data support the postulates that OVAR generates compensatory eye velocity through activation of velocity storage and that oscillatory components arise predominantly through lVOR orientation mechanisms.
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PMID:Compensatory and orienting eye movements induced by off-vertical axis rotation (OVAR) in monkeys. 1242 85

We compared the horizontal optokinetic reaction (OKR) and response properties of retinal slip neurons in the nucleus of the optic tract and dorsal terminal nucleus (NOT-DTN) of albino and wild-type ferrets (Mustela putorius furo). In contrast to pigmented ferrets, we were unable to observe OKR in albino ferrets during binocular and monocular viewing using random dot full field stimulation and electro-oculography (EOG). Observations during early postnatal life indicate that regular OKR is present in pigmented pups 3 d after eye opening but is absent at any stage during development in albino ferrets. Unilateral muscimol injections to inactivate all neurons in the NOT-DTN containing GABA(A) and GABA(C) receptors caused spontaneous horizontal nystagmus with slow phases away from the injected hemisphere in albino as well as in pigmented animals. Retinal slip neurons in the NOT-DTN of albino ferrets identified by antidromic activation from the inferior olive and orthodromic activation from the optic chiasm were well responding to intermittent bright light stimuli, but many showed a profound reduction of responsiveness to moving stimuli. The movement-sensitive neurons exhibited no clear direction selectivity for ipsiversive stimulus movement, a characteristic property of these neurons in pigmented ferrets and other mammals. Thus, the defect rendering albino ferrets optokinetically nonresponsive is located in the visual pathway subserving the OKR, namely in or before the NOT-DTN, and not in oculomotor centers.
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PMID:Optokinetic deficits in albino ferrets (Mustela putorius furo): a behavioral and electrophysiological study. 1510 21


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