Introduction: Ocular dysfunctions and toxicities induced by antiepileptic drugs (AEDs) are rarely reviewed and not frequently received attention by treating physicians compared to other adverse effects (e.g. endocrinologic, cognitive and metabolic). However, some are frequent and progressive even in therapeutic concentrations or result in permanent blindness. Although some adverse effects are non-specific, others are related to the specific pharmacodynamics of the drug.
Areas covered: This review was written after detailed search in PubMed, EMBASE, ISI web, SciELO, Scopus, and Cochrane Central Register databases (from 1970 to 2019). It summarized the reported ophthalmologic adverse effects of the currently available AEDs; their risks and possible pathogenic mechanisms. They include ocular motility dysfunctions, retinopathy, maculopathy, glaucoma, myopia, optic neuropathy, and impaired retinal vascular autoregulation. In general, ophthalmo-neuro- or retino-toxic adverse effects of AEDs are classified as type A (dose-dependent), type B (host-dependent or idiosyncratic) or type C which is due to the cumulative effect from long-term use.
Expert opinion: Ocular adverse effects of AEDs are rarely reviewed although some are frequent or may result in permanent blindness. Increasing knowledge of their incidence and improving understanding of their risks and pathogenic mechanisms are crucial for monitoring, prevention, and management of patients’ at risk. 相似文献
Interneurons immunoreactive for vasoactive intestinal polypeptide (VIP) are integral elements of columnar organization patterns in the rat cerebral cortex. By application of the sensitive mirror technique, the co-localization of VIP with the classical inhibitory neurotransmitter γ-aminobutyric acid (GABA) and the acetylcholine-synthesizing enzyme, choline acetyltransferase (ChAT), was investigated in neocortical neurons. Furthermore, the frequency of co-localization of ChAT with GABA was determined. In a sample of 118 VIP-immunoreactive neurons, mostly from the primary somatosensory cortex, it was demonstrated that virtually all of them reveal immunoreactivity for GABA and, therefore, are to be GABAergic. Moreover, 34% of mostly bipolar, VIP-positive neurons contained ChAT and are, thus, supposedly cholinergic as well. Co-localization of VIP and ChAT varied according to cortical laminae. Finally, 88% of a total of 60 ChAT-immunoreactive neurons were also immunostained for GABA. It is concluded that almost all VIP-immunoreactive neurons and most of the cholinergic neurons in rat neocortex represent partly overlapping subpopulations of inhibitory interneurons utilizing GABA. 相似文献
While adult mice receiving picrotoxin (PTX) alone responded with clonic and tonic-clonic seizures, this response was greatly suppressed for mice simultaneously injected with 2,3-butanedione monoxime (BDM). For example, 60% and 10% of the mice convulsed when injected (i.p.) with 3.0 mg/kg PTX alone or PTX plus 205 mg/kg of BDM, respectively. In contrast, a non-oxime analogue of BDM, 2,3-butanedione (BTD), did not have this anticonvulsant effect. In order to explore the basis for the anticonvulsant effect of BDM, we recorded GABA-activated currents (IGABA) of frontal cortical as well as ventromedial hypothalamic neurons before, during and after exposure to this oxime. BDM had a biphasic effect on concentrations (100 μM-40 mM) decreased and lower concentrations (0.01 μM–0.001 μM) potentiatedIGABA; these effects of BDM reversed upon washout of the oxime. In contrast, BTD had no effect onIGABA. Finally, when 0.001 μM BDM, 10–30 μM PTX and GABA were co-applied the inhibitory effect of the toxin onIGABA was markedly suppressed. These data suggest that the anticonvulsant effect of oximes involves facilitation of the inhibitory action of GABA. 相似文献
Whole-cell voltage clamp recordings in 400 microns thick hippocampal slices revealed discrete excitatory and inhibitory postsynaptic currents which persisted at synapses on granule cells following abolition of action potentials with 1 microM tetrodotoxin (TTX). The conductances associated with excitatory amino acid and GABAA receptor mediated events had mean peaks of 200 and 800 pS, and decayed monoexponentially with time constants of 5.6 and 5.3 ms. At a holding potential close to the normal resting membrane potential of granule cells (-80 to -90 mV), the frequency of glutamate/aspartate mediated spontaneous excitatory postsynaptic currents (sEPSCs) was decreased from 2.04 Hz in slices cut parallel to the plane of the perforant path to 0.87 Hz in slices cut in a plane that disrupted the distal perforant path fibres, suggesting that presynaptic integrity influences the rate of action potential independent neurotransmitter release. The orientation of the slicing had no effect on the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs). 相似文献
The synaptic organization of the projection from the cat striate visual cortex to the posteromedial lateral suprasylvian cortical area (PMLS) was examined. The anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) was iontophorectically delivered into area 17, and anterogradely labeled fibers were revealed in PMLS by means of an immunocytochemical detection method. Most axons and presumptive terminal swellings were found in layers III and IV. The neuronal elements (n = 190) that were postsynaptic to anterogradely labeled boutons were quantitatively analyzed. All anterogradely labeled cortico-cortical boutons (n = 182) established type 1 synapses. The results show that 83% of the postsynaptic targets were dendritic spines, probably belonging to pyramidal cells. Dendritic shafts constituted 17% of the targets. The dendritic shafts postsynaptic to cortico-cortical boutons were studied for the presence of gamma-aminobutyric acid (GABA) with a postembedding immunogold method. Most dendritic shafts (85%) that were tested were found to be GABA-positive, demonstrating that they originate from local inhibitory neurons. Taking into account that most postsynaptic targets were spines and extending the results of the immunocytochemical testing to the total population of postsynaptic dendrites, it was calculated that at least 14% of targets originated from GABA-positive cells. Thus cortico-cortical axons establish direct monosynpatic connections mainly with pyramidal and to a lesser extent with GABAergic nonpyramidal neurons in area PMLS, providing both feedforward excitation and feedforward inhibition to a visual associational area known to be involved in the processing of motion information. The results are consistent with previously demonstrated deficits in physiological properties of neurons in PMLS following removal of cortico-cortical afferents. 相似文献
The disector, an unbiased stereological method for evaluation of synaptic densities, was used to analyse putative GABA and glutamate innervations of the supraoptic nucleus of virgin and lactating rats. The analysis was performed on ultrathin sections labelled for either of the amino acids with a postembedding immunogold technique. Our observations showed that the volume of the nucleus increased by 40% in lactating animals, an increase due to a significant enlargment of dendritic and somatic, but not vascular, volumes. Nevertheless, values of overall synaptic densities in the whole nucleus remained as high as those in virgin rats (37–40×106 synapses/mm3). About 45% of all synapses were immunoreactive for GABA and 25% for glutamate; there were twice as many GABA- and glutamate-positive synapses on dendrites as on somata. When we estimated synaptic densities in relation to the neuropil (by subtracting the proportion of sampled areas occupied by somatic profiles), we found a significant increase in synaptic density in lactating animals. This affected axodendritic as well as axosomatic synapses, immunopositive and immunonegative for GABA or glutamate. The disector also allowed us to determine that the number of synapses from terminals making contacts on several somata and/or dendrites simultaneously constituted about 9% of all synapses in virgin rats, a proportion which more than doubled in lactating rats. About 50% were immunopositive for GABA and 30% for glutamate.
Our data offer further evidence of physiologically-linked structural synaptic plasticity in the supraoptic nucleus and clearly demonstrate that it affects both inhibitory and excitatory inputs on dendrites, as well as on somata, throughout the nucleus. 相似文献