Charles Bonnet syndrome (visual hallucinations) following enucleation.
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Eye Enucleation↗
Biomedical subjects
B A Sabel
Publications and source records attributed to B A Sabel.
Does visual restitution training change absolute homonymous visual field defects? A fundus controlled study.
AIM: To examine whether visual restitution training (VRT) is able to change absolute homonymous field defect, assessed with fundus controlled microperimetry, in patients with hemianopia. METHODS: 17 patients with stable homonymous visual field defects before and after a 6 month VRT period were investigated with a specialised microperimetric method using a scanning laser ophthalmoscope (SLO). Fixation was controlled by SLO fundus monitoring. The size of the field defect was quantified by calculating the ratio of the number of absolute defects and the number of test points; the training effect E was defined as the difference between these two ratios before and after training. A shift of the entire vertical visual field border by 1 degrees would result in an E value of 0.14. RESULTS: The mean training effect of all right eyes was E = 0.025 (SD 0.052) and all left eyes E = 0.008 (SD 0.034). In one eye, a slight non-homonymous improvement along the horizontal meridian occurred. CONCLUSIONS: In one patient, a slight improvement along the horizontal meridian was found in one eye. In none of the patients was an explicit homonymous change of the absolute field defect border observed after training.
Adult↗
Vision restoration therapy.
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Hemianopsia↗
L-type calcium channel antagonist nifedipine reduces neurofilament restitution following traumatic optic nerve injury.
BACKGROUND: The aim of the present study was to observe if the use of the L-type calcium channel antagonist nifedipine would offer advantages for the retinal ganglion cells and the restitution of the axonal cytoskeleton after optic nerve crush. METHODS: Retinal ganglion cells were retrogradely labeled with a fluorescent calcium marker. With the in vivo confocal neuroimaging (ICON) method we observed the fluorescent cell metabolism marker Oregon Green BAPTA in the same retinal ganglion cells over 3 weeks after optic nerve crush. 2 micromol nifedipine were injected intraocularly 30 minutes following optic nerve crush. FINDINGS: Investigation of the optic nerve immunostained for NF-H presented decreased restitution of the neurofilaments in the axonal cytoskeleton after 3 weeks in the optic nerve crush group treated with nifedipine as compared to the optic nerve crush only group. INTERPRETATION: These results show that a single injection of the calcium L-type antagonist nifedipine shortly after optic nerve injury has long-lasting negative effects on the recovery of the retinal ganglion cells.
Animals↗
Protease-activated receptor subtype expression in developing eye and adult retina of the rat after optic nerve crush.
Protease-activated receptors (PARs), 7-transmembrane domain G protein-coupled receptors, are involved in tissue degeneration and repair upon injury. We demonstrate the expression of all four PAR subtypes in the postnatal eye and in retina of the adult rat by reverse transcription-polymerase chain reaction (RT-PCR). PAR-1 is regulated developmentally in the eye, with a decrease from P1, P9, to P16, whereas levels for PAR-2, PAR-3, and PAR-4 remain unchanged throughout. In the retina of the adult rat, PAR-1 is highly expressed, whereas PAR-2 and PAR-3 are moderately expressed, compared to low PAR-4 expression. To elucidate possible roles of PARs after trauma, we carried out semiquantitative RT-PCR analysis of expression of all 4 PAR subtypes, beginning 6 hr after partial optic nerve crush (ONC) in the adult rat until 3 weeks after the mild trauma. Levels of PAR mRNA for all four subtypes were upregulated as early as 6 hr after unilateral ONC, except PAR-3, which showed a delayed upregulation. PAR-1, PAR-3, and PAR-4 mRNA levels returned to almost basal levels at 3 weeks post-crush, whereas PAR-2 mRNA level was still high by the end of 3 weeks after crush. Although the lesion was unilateral, PAR mRNA expression in the contralateral, uninjured side was affected to levels almost comparable to those in the injured side. Previous studies have shown an increase in thrombin levels at the site of injury, retinal ganglion cell degeneration by necrosis and apoptosis, and PAR activation as consequences of nerve crush. PAR upregulation because of nerve crush in the mild trauma model could act as an effector of early cell death. Eventual return of receptor mRNA to basal levels is consistent with neuroprotection.
Animals↗
Anatomical correlations of intrinsic axon repair after partial optic nerve crush in rats.
About 15% of retinal ganglion cells survive diffuse axonal injury of the optic nerve in adult rats. Following initial blindness, discrimination of visual stimuli in behavioral tests recovers within three weeks. To investigate the mechanisms promoting this functional recovery the axonal transport and the neurofilaments were studied. Intraocularly applied MiniRuby is transported until the place of crush and accumulated in enlarged axon terminals. Three weeks after lesion the anterograde transport of MiniRuby recovers distal to the place of crush. At the same point in time the retrograde transport of surviving retinal ganglion cells is restored which was visualized by horseradish peroxidase injected into the superior colliculus. The heavy neurofilament was stained immunohistochemically and analyzed statistically up to three weeks after optic nerve crush. The stained filaments in the axon fibers of retinal ganglion cells appear wavelike and/or fragmented up to day 8, but first signs of heavy neurofilament restitution in the fibers of the optic nerve are seen at day 12 after axonal injury. Because these results cannot be explained by longlasting axon regeneration, the present results provide convincing evidence for intrinsic axon repair soon after diffuse axonal injury that correlates in time with recovery of vision.
Animals↗
Acute effects of alcohol on divided and covert attention in men.
RATIONALE: While several studies identified divided attention to be sensitive to alcohol effects, the impact of alcohol on covert visual attention is still not clear, despite the latter's important role in perception. OBJECTIVES: The study tests the effect of acute moderate doses of alcohol on divided and covert attention in right-handed, male volunteers. METHODS: The design of the study involved a double-blind trial with an alcohol and a placebo condition; measurements were taken before and after an oral dose of 0.6 g/kg alcohol versus placebo. In the divided-attention task, simultaneous visuo-spatial and auditory stimulation was applied. In a test of covert attention, subjects had to shift their attentional focus according to a central cue, from one location in the visual field to another. RESULTS: Under the divided-attention condition, reaction times were significantly prolonged after alcohol ingestion compared to placebo. Covert attention pre-post change was also significantly different between the alcohol and placebo groups. There is a reduction of false-cueing disturbance for left-appearing stimuli under moderate alcohol but an increase of disturbance for rightward stimuli, i.e. we found a lateralised pattern of reaction for spatial orienting. In the placebo group, no significant differences in right-left performance were obtained. CONCLUSION: The results suggest that sensory-attentional mechanisms play a key role in altered visual perceptual performance after alcohol ingestion. Furthermore, differences between the right and left visual field in the cued target-detection task indicate that alcohol exerts an influence on right-hemispheric attentional priming.
Adult↗
Deficits of respiratory-cardiac coupling in heavy drinkers.
1. Physiological evidence of chronic alcohol abuse prior to the onset of clinical signs of alcohol dependence is difficult to obtain The purpose of this study was to search for possible non-invasive indicators for chronic alcohol consumption yielding information in addition to conventional biological markers. 2. The authors investigated the relationship between respiratory-cardiac coupling and blood alcohol concentration (BAC) in male subjects who lost their driver's license from drunk driving. 3. We found that subjects who had a high BAC level (0.16-0.31% at the time of offense) show altered respiratory sinus arrhythmia (RSA) and, in particular, an altered heart-rate response to auditory stimulation and compared them to a control group of social drinkers. Normal subjects showed a pronounced acoustic heart-rate response, i.e., particularly during expiration there was a difference between the interbeat-interval (IBI) traces with and without auditory stimulation. Subjects who had lost their driver's license from drunk driving had an overall severely reduced heart-rate response, that was even absent particularly in the subgroup having high BAC values (0.21-0.31%). The authors also found some evidence that in the latter subgroup IBI, RSA, and acoustic heart-rate responses partially recover after a six-month period of abstinence. 4. Specific parameters of the acoustic heart-rate response are changed in our group of alcohol abusers presumably, due to impairment of vagal function. These parameters may therefore be useful to serve as a non-invasive measure of alcohol abuse.
Accidents, Traffic↗
Stability of visual field enlargements following computer-based restitution training -- results of a follow-up.
In a previous randomized placebo-controlled clinical trial, we observed significant visual field enlargements induced by computer-based restitution training in patients with cerebral lesions (Kasten et al., Nature med., 4, 1998, 1083-87). Now we asked the question whether this effect is stable after training was discontinued? Here we report data of a follow-up study after a training-free interval (mean 23.5 +/- 2.3 months after end of therapy). 16 patients of the original restitution group and 6 patients of the placebo group were re-examined. On average, in high resolution computer campimetry (stimulus detection: PeriMa, form recognition: PeriForm, color perception: PeriColor) as well as in conventional automatic perimetry (TAP-2000) both groups showed no significant decline in the number of correctly detected stimuli after training was discontinued. However, cluster analysis revealed three different types of patients, who showed either increase (Type-I), decrease (Type-II) or stability (Type-III) in performance. We propose that many patients learn to use the regained visual capacities not only in the setting of a computer training but also in every day life, while other patients do not use the areas of restored vision and show a decrease of visual functions after the end of training. The Type-I group does not need continuous training, while the Type-II group may benefit from phases of refreshment exercises.
Adult↗
Unusual spontaneous and training induced visual field recovery in a patient with a gunshot lesion.
Over a period of more than 3 years, changes in visual and neuropsychological functions were examined in a patient with a visual field defect caused by a cerebral gunshot lesion. Initially, the patient had been completely blind, but after 6 months of spontaneous recovery, he showed a homonymous bilateral lower quadrantanopia and impairment of higher visual functions. Unexpectedly, recovery still continued after the first 6 months. This process was documented in detail by visual field examinations using high resolution perimetry. When visual field size had stabilised almost 16 months after the lesion, further improvement could be achieved by visual restitution training. The duration and extent of spontaneous recovery were unusual. In spontaneous as well as in training induced recovery, progress was mainly seen in partially defective areas (areas of residual vision) along the visual field border. Thus, it is speculated that modulation of perceptual thresholds in transition zones of visual field defects contributes to spontaneous and training induced recovery.
Adult↗
Restoration of vision IV: role of compensatory soma swelling of surviving retinal ganglion cells in recovery of vision after optic nerve crush.
PURPOSE: Diffuse axonal injury following partial optic nerve crush (ONC) leads to severe visual deficits from which rats can partially recover within 2-3 weeks. To evaluate tbc role of surviving retinal ganglion cells (RGCS) in recovery, we have observed their morphology repeatedly in vivo with ICON-microscopy and correlated cell size changes with recovery of vision which we observed in parallel in the same animals. METHODS: After rats had learned a visual contrast discrimination task using an automated, computer-based test, RGCs were labeled retrogradely with fluorescent beads. Animals then received either no lesion, a complete axotomy or bilateral mild, moderate or severe ONC. Before surgery and for 40 days post-operatively, ROC number and soma size was repeatedly quantified every five days with tbc in vivo confocal neuroimaging method (Sabel et al., Nature med. 3, 1997, p. 244). In parallel, visual function was quantified with the contrast-discrimination task. RESULTS: After ONC about 70 % of the ROCs died after having undergone a fast and massive soma swelling. The extent of cell death was independent of crush severity. RGCs surviving the injury did not change their body size over time in the severe group and these animals also did not recover their vision. In contrast, after a mild or moderate crush, about half of the surviving RGCs experienced a slow and moderate, "compensatory" cell soma swelling and the rats showed partial recovery of vision. Both the number of RGCs showing such compensatory soma swelling and the extent of the swelling correlated highly (r = 0.96) with recovery of contrast discrimination performance at post-operative days 23 and 38. CONCLUSIONS: Depending en the time course and extent, soma swelling after neurotrauma may be associated either with cell death or recovery of function. Because of the very high correlation between extent of recovery and amount of soma swelling, moderate soma swelling contributes in a prominent way to recovery of vision. We believe that these cells provide an important structural substrate for neuronal tissue repair and therefore term these cells "compensatory neurons".
Adaptation, Physiological↗
Assessing spatial vision - automated measurement of the contrast-sensitivity function in the hooded rat.
The contrast-sensitivity function (CSF) provides a concise and thorough description of an organism's spatial vision; it is widely used to describe vision in animals and humans, to track developmental changes in vision, and to compare vision among different species. Despite the predominance of rats in neuroscience research, their vision is not thoroughly studied due to the complexity of psychophysical measurement and a generally held notion that rat vision is poor. We therefore designed an economical and rapid method to assess the hooded rat's CSF, using a computer monitor to display stimuli and an infrared touch screen to record responses. A six-alternative forced-choice task presented trials in which a sine-wave grating (S+), varying in spatial frequency and contrast, was displayed at different locations along with five gray stimuli (S-). Nose pokes to the S+ but not the S- produced water reinforcers. Contrasts were tested at each spatial frequency with a simple adaptive procedure until stimulus detection fell below chance. Psychometric functions were obtained by maximum-likelihood fitting of a logistic function to the raw data, obtaining the threshold as the function's point of inflection. As in previous studies with rats, CSFs showed an inverse-U shape with peak sensitivity at 0.12 cyc/deg and acuity just under 1 cyc/deg. The results indicate the present computer-controlled behavioral testing device is a precise and efficient instrument to assess spatial visual function in rats.
Animals↗
Quinolinic acid released from polymeric brain implants causes behavioral and neuroanatomical alterations in a rodent model of Huntington's disease.
Quinolinic acid (QA) is an N-methyl-d-aspartate agonist that has been shown to produce neurotoxic effects that mimic certain neurodegenerative diseases when administered to laboratory animals. Intrastriatal injections of QA in rats have been used extensively to produce some of the neuropathological and behavioral deficits that are analogous to Huntington's disease (HD). However, acute intrastriatal injections of QA produce symptoms that are not analogous to the progressive nature of HD. Thus far, models using chronic administration of QA that produce HD-like behavioral and neuroanatomical changes have necessitated the use of a relatively bulky and fragile microdialytic pump apparatus. The present study tested an alternative way of chronically administering QA. Specifically, this study tested whether gradual release of QA from ethylene vinylacetate (EVA) polymers could produce symptoms analogous to HD. Rats received either no implants or bilateral intrastriatal implants of polymers with or without QA. Subsequent tests for spontaneous motor activity (SMA), grip strength, balance, and learning ability in a radial-arm-water-maze task revealed QA-induced impairments in balance and learning ability, but did not affect grip strength or SMA. Histological analysis revealed QA-induced enlargement of lateral ventricles, striatal atrophy, and striatal neuronal loss, with relative sparing of NADPH-diaphorase-positive neurons. These results suggest that QA released from polymers can produce behavioral and neuropathological profiles analogous to early stages of HD and that EVA polymers offer a useful means of chronically delivering QA in rodent models of neurodegeneration.
Animals↗
Body distribution of 3H-labelled dalargin bound to poly(butyl cyanoacrylate) nanoparticles after i.v. injections to mice.
The blood-brain barrier (BBB) limits the penetration of substances into the brain. Because many drugs, particularly peptides, therefore can not be delivered to the brain, carrier systems were developed to overcome this problem. In earlier studies we demonstrated central analgesic effects of a peptide, dalargin (dal), after systemic administration when this substance was bound onto the surface of polybutylcyanoacrylate nanoparticles and coated with polysorbate 80 but not when it was given alone. The aim of the present study was to investigate the body distribution of 3H-labelled dal bound to nanoparticles compared to unbound dal after i.v. injection in mice. The radioactivity in several tissues, including the brain, was separated in subcellular preparations and was measured after a single i.v. injection over time. Dal radioactivity level in brain preparations was 3 times higher when the drug was bound to nanoparticles whereas the first pass pathway in liver was reduced. The results support previous data that nanoparticles can be used to transport peptides across the BBB.
Animals↗
Neuroleptics ameliorate phencyclidine-induced impairments of short-term memory.
1. Phencyclidine (PCP), a non-competitive NMDA-receptor antagonist, is able to induce schizophrenia-like symptoms in animals and in humans. It is known that schizophrenic patients have deficits in memory processes. 2. Therefore, it was investigated whether subchronic pulsatile or continuous application of 5.0 mg kg(-1) PCP over 5 days induce short-term memory deficits in holeboard learning and the action of two different neuroleptics on this behavioural test. 3. First, an impairment in the holeboard task was described when the animals were tested 24 h after the last application but not after 15 min or 1 h after the last injection. Secondly, the influence of haloperidol and risperidone on the PCP-induced short-term memory changes was tested. 4. The combined application of PCP and risperidone led to a complete antagonism of the short-term deficits, but the combined treatment with haloperidol was accompanied by a partial abolishment of the PCP-induced deficits. 5. PCP led to an upregulation of the glutamate binding sites in striatum and nucleus accumbens whereas the D(2) binding sites were reduced in striatum. The D(1) binding sites seem to be unchanged. The receptor protein expression of glutamate receptors mGluR1, GluR2, GluR5/7 and NMDAR1 were not modified in response to PCP treatment. 6. The determination of a subpopulation of GABAergic interneurons shows a decrease of the cells within the CA3 of the hippocampal formation. 7. These findings indicate that PCP induced impairments in short term memory can be detected by holeboard learning and may provide an interesting tool for the search of new neuroleptics.
Animals↗
Restoration of vision by training of residual functions.
A new paradigm emerges: visual field defects after optic nerve or brain injury are partially reversible. Using high-resolution visual field tests, areas of residual vision can be identified which are characterized by impaired vision (relative defect) with some residual capacities. By repetitively stimulating these partially damaged areas with daily computer-based visual restitution training it is now possible to enlarge the visual field. Average border shifts of 5 degrees (range, 0 to 20 degrees) have been found in clinical trials, and training is effective even when started years after the injury. Visual restitution training is useful for the treatment of patients with stroke, head injury, or partial optic nerve damage, as long as the patient presents some residual vision. The improved vision is maintained in most patients after training is discontinued. Brain plasticity is likely to provide the substrate for restoration of vision, opening new opportunities to treat partial blindness, which has been considered irreversible.
Animals↗
Computer-based training of stimulus detection improves color and simple pattern recognition in the defective field of hemianopic subjects.
In a previously conducted randomized placebo-controlled trial, we were able to demonstrate significant visual field enlargement induced by restitution therapy in patients with cerebral lesions [Kasten, E., Wuest, S., Behrens-Bamann, W., & Sabel, B. A. (1998c). Computer-based training for the treatment of partial blindness. Nature Medicine, 4, 1083-1087.]. Visual field training was performed on a computer monitor for 1 hr per day over a period of 6 months. Since the procedure included only stimulation with white light, in the present study we investigated if this simple detection training had a transfer effect on color or form recognition in the trained area (i.e., in the absence of modality specific training). Answering this question would be crucial for planning optimal restitution therapy: In case there is no transfer of training effects to other visual modalities, a specific treatment of each visual function must be performed in order to achieve maximum benefit. Therefore, we analyzed the data from 32 patients with visual field defects who had participated in the original trial and whose form and color recognition had been investigated. The experimental group (n = 19, restitution training) experienced not only an increase of 12.8% correctly detected stimuli (PeriMa program, p <.05), but also an improvement of 5.6% in pattern recognition (PeriForm) and of 6.1% in color perception (PeriColor), respectively. In contrast, the placebo group (n = 13, fixation training) showed no significant changes from baseline to final outcome in any of the visual modalities (PeriMa: 0.3%; PeriForm: -0.3%; PeriColor: 0.4%). Conventional perimetry yielded an increase of 7.8% detected stimuli in the experimental group, but only of 1.2% in the placebo group (p <.05). For form recognition and color perception, the differences between the results of the experimental and the placebo groups narrowly missed significance. However, correlations of diagnostic results showed that mainly those patients who had achieved visual field enlargement also improved in color and form perception: r =.67 (p <.05) between PeriMa and PeriForm and r =.32 between PeriMa and PeriColor. We conclude that visual restitution training using a simple white light stimulus has at least some influence on improving other visual functions such as color and pattern recognition. This result supports the "bottleneck theory" of visual restitution, i.e., training effects can be explained as a process of perceptual learning and increased processing of information by residual structures surviving lesions of the primary visual pathways.
Audiovisual Aids↗
Influence of nanoparticles on the brain-to-serum distribution and the metabolism of valproic acid in mice.
The suitability of nanoparticles as a drug-carrier system for the antiepileptic valproic acid has been studied in mice. The aim of the study was to increase the brain-to-serum ratio of the drug to reduce dose-related side effects in the periphery. The influence of nanoparticles on the metabolism of valproic acid was also investigated. The serum kinetics and the brain tissue levels of valproic acid were not altered by administration with nanoparticles. However, the nanoparticles did inhibit the metabolic degradation of valproic acid via mitochondrial beta-oxidation but did not influence any other metabolic pathway. It can be concluded that nanoparticles loaded with valproic acid may help to reduce the toxic side effects of valproate therapy, not by reducing the therapeutically necessary dosage but by inhibition of formation of toxic metabolites. Using their ability to selectively block a pathway nanoparticles may serve as a tool to investigate the metabolic origin of metabolites and their contribution to therapeutic efficacy and side effects.
Animals↗