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      Respuesta de una subpoblación de interneuronas y del transportador glial de glutamato GLT1 en la corteza contralateral a un foco isquémico Translated title: Contralateral cortical response of a subpopulation of interneurons and the glial glutamate transporter GLT1 to an ischemic core

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          Abstract

          Introducción: La isquemia cerebral es una de las formas de lesión cerebral mas frecuentes en el humano. Usualmente los investigadores cuando estudian su fisiopatología se centran en las áreas directamente comprometidas: región del foco, o en las zonas de penumbra, olvidando otros sectores vecinos o no del foco que están conectados con estos sectores de injuria, los cuales pueden estar implicados en algunos de los síntomas que se observan en los pacientes que sufren procesos isquémicos. Objetivo: Evaluar el comportamiento laminar de una subpoblación de interneuronas y de la población glial de la corteza cerebral contralateral al foco isquémico, a través de los marcadores parvalbúmina (PV), que detecta neuronas gabaérgicas y del transportador glial de glutamato GLT1. Materiales y métodos: Se ocluyó la arteria cerebral media derecha en ratas macho adultas, durante 90 minutos, utilizando una sutura intraluminal. Los animales se sacrificaron a las 24 y 72 horas post isquemia. El análisis se hizo en la corteza contralateral al foco, identificando interneuronas PV positivas y la expresión en astrocitos del transportador GLT1. Resultados: Se encontró disminución significativa de la marcación del transportador de glutamato, GLT1, en las capas III y IV de la corteza contralateral al foco isquémico y un aumento en la expresión de PV en las capas II a V comparado con los animales controles. Conclusiones: Los cambios en la expresión de GLT1 pueden proveer un nuevo estado de regulación de glutamato y un patrón diferente de actividad en áreas remotas a un foco isquémico. El aumento en la expresión de PV puede corresponder a un mecanismo adaptativo asociado al incremento de glutamato, por la disminución del transportador, en las envolturas gliales de las sinapsis. Este estudio representa un ejemplo de plasticidad neuronal y glial en zonas remotas al foco isquémico pero conectadas con el mismo.

          Translated abstract

          Introduction: Cerebral ischemia is an important cause of brain lesion in humans. The target in research has been the ischemic core or the penumbra zones; little attention has been given to areas outside the core or the penumbra but connected with the primary site of injury. Objective: Evaluate the laminar response of a subpopulation of gabaergic cells, those that are parvalbumin (PV) positive and the astrocytes through the expression of the glial transporter GLT1 on the contralateral cortex to an ischemic core. Methodology: For this purpose we used the medial cerebral artery occlusion model in rats. The artery was occluded for 90 minutes and the animals were sacrificed at 24 and 72 hours post-ischemia. The brains were removed, cut in a vibratome at 50 microns and incubated with the primary antibodies against PV or GLT1. Sections were developed using the vectastain Kit. In control tissue the primary antibody was omitted. Results: When compared with control animals, treated ones show a decrease in the expression of GLT1, especially in layers III and IV of the contralateral cortex to the ischemic core. PV positive cells increases in layers II and V. Conclusion: Increases in the expression of PV cells could correspond to an adaptation associated with glutamate increases in the synaptic compartment. These increases may be due to decreases in the expression of GLT1 transporter, that could not remove the glutamate present in the synaptic cleft, generating hyperactivity in the contralateral cortex. These changes could represent an example of neuronal and glial plasticity in remote areas to an ischemic core but connected to the primary site of injury.

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          Most cited references 29

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          Cellular distribution of the calcium-binding proteins parvalbumin, calbindin, and calretinin in the neocortex of mammals: phylogenetic and developmental patterns.

          The three calcium-binding proteins parvalbumin, calbindin, and calretinin are found in morphologically distinct classes of inhibitory interneurons as well as in some pyramidal neurons in the mammalian neocortex. Although there is a wide variability in the qualitative and quantitative characteristics of the neocortical subpopulations of calcium-binding protein-immunoreactive neurons in mammals, most of the available data show that there is a fundamental similarity among the mammalian species investigated so far, in terms of the distribution of parvalbumin, calbindin, and calretinin across the depth of the neocortex. Thus, calbindin- and calretinin-immunoreactive neurons are predominant in layers II and III, but are present across all cortical layers, whereas parvalbumin-immunoreactive neurons are more prevalent in the middle and lower cortical layers. These different neuronal populations have well defined regional and laminar distribution, neurochemical characteristics and synaptic connections, and each of these cell types displays a particular developmental sequence. Most of the available data on the development, distribution and morphological characteristics of these calcium-binding proteins are from studies in common laboratory animals such as the rat, mouse, cat, macaque monkey, as well as from postmortem analyses in humans, but there are virtually no data on other species aside of a few incidental reports. In the context of the evolution of mammalian neocortex, the distribution and morphological characteristics of calcium-binding protein-immunoreactive neurons may help defining taxon-specific patterns that may be used as reliable phylogenetic traits. It would be interesting to extend such neurochemical analyses of neuronal subpopulations to other species to assess the degree to which neurochemical specialization of particular neuronal subtypes, as well as their regional and laminar distribution in the cerebral cortex, may represent sets of derived features in any given mammalian order. This could be particularly interesting in view of the consistent differences in neurochemical typology observed in considerably divergent orders such as cetaceans and certain families of insectivores and metatherians, as well as in monotremes. The present article provides an overview of calcium-binding protein distribution across a large number of representative mammalian species and a review of their developmental patterns in the species where data are available. This analysis demonstrates that while it is likely that the developmental patterns are quite consistent across species, at least based on the limited number of species for which ontogenetic data exist, the distribution and morphology of calcium-binding protein-containingneurons varies substantially among mammalian orders and that certain species show highly divergent patterns compared to closely related taxa. Interestingly, primates, carnivores, rodents and tree shrews appear closely related on the basis of the observed patterns, marsupials show some affinities with that group, whereas prototherians have unique patterns. Our findings also support the relationships of cetaceans and ungulates, and demonstrates possible affinities between carnivores and ungulates, as well as the existence of common, probably primitive, traits in cetaceans and insectivores.
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            High affinity glutamate transporters: regulation of expression and activity.

            L-Glutamic acid is a major excitatory neurotransmitter in the mammalian central nervous system. The termination of the glutamatergic transmission and the clearance of the excessive, neurotoxic concentrations of glutamate is ensured by a high affinity glutamate uptake system. Four homologous types of Na/K-dependent high affinity glutamate transporters, glutamate/aspartate transporter, glutamate transporter 1, excitatory amino acid carrier 1, and excitatory amino acid transporter 4, have recently been cloned and were assigned to a separate gene family, together with two neutral amino acid carriers, alanine/serine/cysteine transporter 1/serine/alanine/threonine transporter and adipocyte amino acid transporter. The genomic organization of these transporters is still under investigation. Very little is known about the nature of the factors and molecular mechanisms that regulate developmental, regional, and cell type-specific expression of the glutamate transporters and their aberrant functioning in neurodegenerative diseases (e.g., amyotrophic lateral sclerosis and Alzheimer's disease). Some experimental conditions (e.g., ischemia, corticostriatal lesions, hyperosmolarity, culturing conditions) and several naturally occurring and synthetic compounds (e.g., glutamate receptor agonists, dopamine, alpha1- and beta-adrenergic agonists, cAMP, phorbol esters, arachidonic acid, nitric oxide, oxygen free radicals, amyloid beta-peptide, tumor necrosis factor-alpha, glucocorticosteroids, unidentified neuronal factors) affect the molecular expression and activity of glutamate transporters. Further elucidation of the molecular events that link epigenetic signals with transcriptional and post-transcriptional mechanisms (e.g., alternative splicing, translation and post-translational modifications) is crucial for the development of selective pharmacological tools and strategies interfering with the expression of the individual glutamate transporters.
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              The influence of depression, social activity, and family stress on functional outcome after stroke.

              This study was designed to assess the quality of life after an active poststroke period of rehabilitation and to investigate the possibility of a return to a working environment for those still of working age. The study was conducted on 180 consecutive patients affected by stroke who were hospitalized for the first time and discharged at least 1 year before the study. The group consisted of 65% men and 35% women with a mean age 65.29 years (SD, 11.22). The period between the stroke and the interview ranged from 12 to 196 months, with a mean of 37.5 months. The average Rankin score on discharge from the rehabilitation center was 2.718 (moderate handicap). The interview took place at home after consent obtained by telephone. The questionnaire included general and personal information regarding the individuals, their socioeconomic position, and scales for daily activity, depression, social activity, and stress produced in the family. The control group consisted of 167 age-matched subjects. A close correlation was observed in all patients between depression, social activity, and stress caused to relatives. The scores on the individual scales were clearly worse than those for control subjects. The patients received approximately 5 months of rehabilitation after the stroke. Differences emerged between men and women for depression and social activities, with the women scoring worse. In reference to daily life, 70% of prestroke ability was required on average after rehabilitation. The daily activity score at the time of the interview was also strongly influenced by the discharge score. The majority of patients were retired. Of the total, 20.64% returned to work, but not always to the same job and often after readapting to new conditions. Of this population, only 31.5% were women. With regard to the population aged younger than 65 years, 21.42% returned to work. Lesions in the dominant hemisphere do not necessarily seem to rule out return to work, even if associated with aphasia. The main discriminating element was the ability to understand language. The patients were often criticized by their cohabitants; the criticisms most often raised concerned apathy, irritability, and self-centeredness. Sexual activity was depressed in almost all cases. Despite the progress made in studying cerebral vasculopathies, patients in the aftermath of a stroke still seem to live unsatisfactorily, as they did many years ago. Useful measures include valid treatment against spasticity, psychological assistance, and greater social support.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Journal
                cm
                Colombia Médica
                Colomb. Med.
                Facultad de Salud, Universidad del Valle, Cali, Colombia (Cali )
                1657-9534
                September 2008
                : 39
                : suppl 3
                : 14-24
                Affiliations
                [1 ] Universidad del Valle Colombia
                [2 ] Universidade de São Paulo Brasil
                Article
                S1657-95342008000700003
                Product
                Product Information: website
                Categories
                MEDICINE, GENERAL & INTERNAL

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