Esclerosis hipocampal: evaluación volumétrica de las subestructuras del hipocampo utilizando resonancia magnética / Hippocampal sclerosis: volumetric evaluation of the substructures of the hippocampus by magnetic resonance imaging

Objetivo: Evaluar las subestructuras hipocampales utilizando resonancia magnética en pacientes con esclerosis hipocampal (EH), comparando los resultados con el análisis morfológico y la volumetría global del hipocampo. Método: Se incluyeron 25 controles y 25 pacientes con EH, cuyo diagnóstico fue extraído del informe de la junta institucional de epilepsia. Se utilizó FreeSurfer para el procesamiento de los estudios y la obtención de los datos volumétricos. El volumen fue valorado de manera global y por subestructura: fimbria, subiculum, presubiculum, fisura hipocampal, CA1, CA2-CA3, CA4 y giro dentado (GD). Se consideró p <0,05 como estadísticamente significativo. Resultados: Se observó una disminución estadísticamente significativa en el hipocampo homolateral al foco epileptógeno en 19 de los 25 casos (76,0%). A excepción de la fisura hipocampal, se observó una disminución en todas las subestructuras hipocampales homolaterales en la EH derecha (CA1, p = 0,0223; CA2-CA3, p = 0,0066; CA4-GD, p = 0,0066; fimbria, p = 0,0046; presubiculum, p = 0,0087; subiculum, p = 0,0017) y la EH izquierda (CA1, p <0,0001; CA2-CA3, p <0,0001; CA4-GD, p <0,0001; fimbria, p = 0,0183; presubiculum, p <0,0001; subiculum, p <0,0001). En cuatro casos de EH izquierda, ninguna de las subestructuras presentó alteración estadísticamente significativa; sin embargo, se observó una tendencia de atrofia, principalmente en CA2-CA3 y CA4-GD. Conclusión: Los hallazgos sugieren la utilidad de la evaluación de las subestructuras hipocampales para mejorar el desempeño de la imagen en el diagnóstico de la EH

Objective: The pathological classification of hippocampal sclerosis is based on the loss of neurons in the substructures of the hippocampus. This study aimed to evaluate these substructures in patients with hippocampal sclerosis by magnetic resonance imaging and to compare the usefulness of this morphological analysis compared to that of volumetric analysis of the entire hippocampus. Material and methods: We included 25 controls and 25 patients with hippocampal sclerosis whose diagnosis was extracted from the institutional epilepsy board. We used FreeSurfer to process the studies and obtain the volumetric data. We evaluated overall volume and volume by substructure: fimbria, subiculum, presubiculum, hippocampal sulcus, CA1, CA2-CA3, CA4, and dentate gyrus (DG). We considered p < 0.05 statistically significant. Results: We observed statistically significant decreases in the volume of the hippocampus ipsilateral to the epileptogenic focus in 19 (76.0%) of the 25 cases. With the exception of the hippocampal sulcus, we observed a decrease in all ipsilateral hippocampal substructures in patients with right hippocampal sclerosis (CA1, p=0.0223; CA2-CA3, p=0.0066; CA4-GD, p=0.0066; fimbria, p=0.0046; presubiculum, p=0.0087; subiculum, p=0.0017) and in those with left hippocampal sclerosis (CA1, p<0.0001; CA2-CA3, p<0. 0001; CA4-GD, p<0. 0001; fimbria, p=0.0183; presubiculum, p<0. 0001; subiculum, p<0. 0001). In four patients with left hippocampal sclerosis, none of the substructures had statistically significant alterations, although a trend toward atrophy was observed, mainly in CA2-CA3 and CA4-GD. Conclusion: The findings suggest that it can be useful to assess the substructures of the hippocampus to improve the performance of diagnostic imaging in patients with hippocampal sclerosis

[Disorders of neurogenesis of cortical and subcortical structures in rat brain limbic system during fetal alcohol syndrome formation].

Disorders of neurogenesis of cortical and subcortical structures in rat brain limbic system were studied in the offspring of rats that received ethanol during pregnancy. The methods used included the staining of histological sections with cresyl violet, in vitro culture, and electron paramagnetic resonance. Prenatal alcohol intoxication was shown to induce the disturbances in proliferative activity of granular layer cells in the hippocampal dentate gyrus, neuron- and glioblast migration, enhancement of free NO and lipoperoxide production and cell death. This resulted in the changes in the number of neurons in cortical and subcortical structures of rat brain limbic system and in fetal alcohol syndrome formation.

Dendritic colocalisation of serotonin1B receptors and the glutamate NMDA receptor subunit NR1 within the hippocampal dentate gyrus: an ultrastructural study.

The serotonin1B receptor (5-HT1BR) plays a significant role in cognitive processing, which also involves glutamatergic transmission via N-methyl-D-aspartate (NMDA) receptors. It is implicated in a range of disorders, many of which also have a cognitive component, and therefore represents a valuable therapeutic target. 5-HT1BRs are described as predominantly pre-synaptic auto- and/or hetero-receptors, modulating the release of neurotransmitters including glutamate. However, a detailed assessment of localisation within the hippocampus, a pivotal structure in cognitive processing, has been absent. Here, we have conducted an electron microscopic examination of the subcellular distribution of the 5-HT1BR, NMDA receptor subunit NR1 and neurotransmitter gamma-aminobutyric acid (GABA), within the hippocampal dentate gyrus. Ultrastructurally, 18% of 5-HT1BR immunoreactivity was pre-synaptic (within axons and axon terminals), and 65% post-synaptic (within dendrites and dendritic spines); no significant differences were found between molecular layer subdivisions. Post-synaptic labelling was cytoplasmic and membranous. Spinous labelling was more frequently bound to the plasma membrane, but not usually directly associated with the synaptic specialisation. Only 16% of 5-HT1BR positive profiles displayed NR1 labelling, of which most were dendrites, at a slightly higher level within the inner, compared to middle and outer molecular layer divisions. 5-HT1BR labelled profiles rarely showed labelling for GABA. These findings indicate that within the dentate gyrus, pre-synaptic 5-HT1BRs may modulate non-GABAergic neurotransmitter release whilst post-synaptic 5-HT1BRs are expressed on segments of mainly NR1 negative granule cell processes. However, a subpopulation of 5-HT1BRs is expressed on NR1 positive dendrites. Here, the 5-HT1BR may be an interesting target for modulation of NMDA receptor mediated currents.

Cellular and subcellular localization of Kir2.1 subunits in neurons and glia in piriform cortex with implications for K+ spatial buffering.

Potassium channels of the Kir2 family are widely expressed in neurons and glia, where they form strong inwardly rectifying channels. Existing functional hypotheses for these channels in neurons are based on the weak outward conductance, whereas the leading hypothesis for glia, that they promote potassium spatial buffering, is based on inward conductance. Although the spatial buffering hypothesis has been confirmed for Müller glia in retina, many aspects of Kir2 channels that will be required for understanding their functional roles in neurons and other forms of glia have received little or no study. Particularly striking is the paucity of data regarding their cellular and subcellular localization. We address this gap for Kir2.1-containing channels by using light and electron microscopic immunocytochemistry. The analysis was of piriform cortex, a highly epileptogenic area of cerebral cortex, where pyramidal cells have K(+)-selective strong inward rectification like that observed in Müller cells, where Kir2.1 is the dominant Kir2 subunit. Pyramidal cells in adult piriform cortex also lack I(h), the mixed Na(+)-K(+) current that mediates a slower form of strong inward rectification in large pyramidal cells in neocortex and hippocampus. The experiments demonstrated surface expression of Kir2.1-containing channels in astrocytes and in multiple populations of pyramidal and nonpyramidal cells. Findings for astrocytes were not consistent with predictions for K(+) spatial buffering over substantial distance. However, findings for pyramidal cells suggest that they could be a conduit for spatially buffering K(+) when it is highly elevated during seizure.

Feedforward inhibition regulates perirhinal transmission of neocortical inputs to the entorhinal cortex: ultrastructural study in guinea pigs.

The rhinal cortices constitute the main route for impulse traffic to and from the hippocampus. Tracing studies have revealed that the perirhinal cortex forms strong reciprocal connections with the neo- and entorhinal cortex (EC). However, physiological investigations indicate that perirhinal transmission of neocortical and EC inputs occurs with a low probability. In search of an explanation for these contradictory findings, we have analyzed synaptic connections in this network by combining injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHAL) into the neocortex, area 36, or area 35 with gamma-aminobutyric acid (GABA) immunocytochemistry and electron microscopic observations. Within area 36, neocortical axon terminals formed only asymmetric synapses, usually with GABA-negative spines (87%), and less frequently with GABA-immunopositive (GABA+) dendrites (13%). A similar synaptic distribution was observed within area 35 except that asymmetric synapses onto GABA+ dendrites were more frequent (23% of synapses). Examination of the projections from area 36 to area 35 and from both regions to the EC revealed an even higher incidence of asymmetric synapses onto GABA+ dendrites (35 and 32%, respectively) than what was observed in the neocortical projection to areas 36 and 35. Furthermore, some of the neocortical and perirhinal terminals containing PHAL and GABA immunolabeling formed symmetric synapses onto GABA-negative dendrites in their projection sites (neocortex to area 35, 16%; area 36 to 35, 7%; areas 36-35 to EC, 12%). Taken together, these findings suggest that impulse transmission through the rhinal circuit is subjected to strong inhibitory influences, reconciling anatomical and physiological data about this network.

Ultrastructure of astrocytes in the cortex of the hippocampal gyrus and in the neocortex of the temporal lobe in experimental valproate encephalopathy and after valproate withdrawal.

The aim of the study was to analyse the astrocyte ultrastructure within the hippocampal gyre cortex and neocortex of the temporal lobe in valproate encephalopathy induced by chronic administration of an anti-epileptic drug - sodium valproate (VPA) to rats for 1, 3, 6, 9 and 12 months, once daily intragastrically, in a dose of 200 mg/kg b.w. and after its withdrawal for 1 and 3 months. Prolonged application of VPA caused damage to protoplasmic astrocytes of the cortex regions examined, mainly in the pyramidal layer, which intensified in the later stages of the experiment, especially after 9 and 12 months. Ultrastructural alterations in astroglia during this experiment did not differ significantly between the hippocampal cortex and neocortex. The most pronounced astroglial abnormalities, concerning about 2/3 of protoplasmic astrocytes after 9 and 12 months, were characterized by considerable swelling of cells, with the presence of empty vacuolar structures in the cytoplasm, a substantial decrease in the number of gliofilaments or even their complete loss, which indicated fibrillopoietic failure of the cell, and the appearance of astrocytes showing phagocytic activity. The astrocytic changes coexisted with distinct damage to neurones and structural elements of the blood-brain barrier. One month after termination of chronic exposure to the drug, the abnormalities did not subside, whereas after 3 months features of distinct normalization could be observed in a considerable number, more than a half, of astrocytes. In valproate encephalopathy, apart from any direct effect of VPA and/or its metabolites on astrocytes, the main cause of the protoplasmic astroglial damage in the cortex of the CNS structures examined could be associated with changes in microcirculation in the cortex (vasogenic factor), leading to its ischaemia.

Cooperation between mglu receptors: a depressing mechanism?

Recent findings from the perirhinal cortex have shed new light on the ways in which metabotropic glutamate receptors could be involved in synaptic plasticity, and in particular in long-term depression (LTD) of synaptic transmission. Importantly, these findings have also led to a greater understanding of mechanisms that could regulate mglu-receptor signalling and the ways in which mglu receptors interact with one another.