Impairment in exploratory behavior is associated with arc gene overexpression in the dorsolateral striatum of rats with nigral injection of l-buthionine sulfoximine.

The aims of the present work were to evaluate the exploratory activity in Sprague-Dawley rats, as well as to analyze the nigral and striatal mRNA expression of the plasticity-related genes bdnf and arc after L-buthionine sulfoximine (BSO) injection into substantia nigra compacta. Lesioned rats traveled less distance in open field but did not show a decline in the novel object recognition test. On the other hand, RT-PCR analysis showed overexpression of striatal arc 24 h post-lesion; no significant changes in bdnf expression were observed in nigral or striatal tissue. These results suggest that intranigral BSO injection causes impairment in exploratory behavior in these rats, by affecting locomotion, which is associated with changes in striatal synaptic plasticity.

Muerte neuronal en la neocorteza de pacientes con epilepsia del lóbulo temporal resistente a fármacos / Neuronal death in the neocortex of drug resistant temporal lobe epilepsy patients

Introducción. La participación de mecanismos de muerteapoptótica en la epilepsia del lóbulo temporal resistente afármacos (ELTRF) es un aspecto muy discutido en la actualidad.Investigamos si existe pérdida neuronal y la inmunodeteccióna diferentes marcadores de muerte en tejido neocorticalen ocho pacientes con ELTRF y como tejido controlse evaluaron cinco neocortezas de sujetos fallecidos porcausas no neurológicas, pareados en edad y sexo.Métodos. La evaluación de la pérdida neuronal se realizópor medio de un estudio estereológico y por técnica inmunohistoquímicacon el marcador sinaptofisina. Se evaluóla inmunopositividad a diferentes marcadores apoptóticos(anexina V, caspasa 3 y 8, bcl-2 y p53), así como la detecciónde fragmentación del ácido desoxirribonucleico (ADN) (TUNEL),y se realizó en todos los casos un doble marcaje con sinaptofisina.Los resultados fueron evaluados por microscopiaconfocal y analizados por el programa Zeiss LSM 5 ImageBrowser, 2.80.1113 (Alemania).Resultados. Se observó una disminución estadísticamentesignificativa del número total de células (p<0,05), asícomo de las células sinaptofisina+ (p<0,01) en la neocorteza(capa IV) de los pacientes con ELTRF al ser comparadoscon el tejido control. No mostraron diferencias significativaslos marcadores apoptóticos bcl-2, p53, caspasa 3 y 8 paraninguna de las capas de neocorteza, mientras que sí resultóestadísticamente aumentado el número de células TUNEL+(p<0,05) y anexina V+ (p<0,05) en la capa IV neocortical delos pacientes.Conclusiones. Este grupo de evidencias hablan a favorde la existencia en la capa IV de neocorteza de una afectaciónen el número neuronal que se puede asociar a un procesode muerte apoptótica por una vía no dependiente de caspasas,sin que pueda ser descartada la muerte por necrosis (AU)

Introduction. Participation of apoptotic death mechanisms in drug resistant temporal lobe epilepsy (DRTLE) is currently under great debate. We have investigated if there is neuronal loss and the immunodetection to differentmarkers in neocortical tissue death in eigth patients with DRTLE. The neocortexes of five patients deceased due to non-neurological causes, paired in age and gender were evaluated as control tissue. Methods. The evaluation of neuronal loss was made by means of a stereological study and with immunohisto chemical techniques with the synaptophysin marker. Immunopositivity to different apoptotic markers (annexin V, caspase 3 and 8, bcl-2 and p53) and detection of deoxyribonucleic acid (DNA) fragmentation (TUNEL) wereanalyzed and double labeling with synaptophysin was performed in every case. The results were evaluated with confocal microscope and analyzed with the Zeiss LSM 5 Image Browser Program, 2.80.1113 (Germany). Results. A statistically significant decrease in the total number of cells (p < 0.05) and the synaptophysin cells+ (p<0.01) in the neocortex (layer IV) of the patients with DRTLE when compared with the control tissue was found. No significant differences were found in the apoptotic markers bcl-2, p53, caspase 3 and 8 for any of the neocortex layers while there was a statistically significantincrease in the number of TUNEL cells+ (p<0.05) and annexin V+ (p<0.05) in the neocortical layer IV of the patients. Conclusions. This group of evidence speaks in favor of the existence of an effect on the neuronal number in the neocortex layer IV that may be associated with non caspase dependent apoptotic death process, without beingable to rule out death by necrosis

[Neuronal death in the neocortex of drug resistant temporal lobe epilepsy patients]. / Muerte neuronal en la neocorteza de pacientes con epilepsia del lóbulo temporal resistente a fármacos.

Introduction. Participation of apoptotic death mechanisms in drug resistant temporal lobe epilepsy (DRTLE) is currently under great debate. We have investigated if there is neuronal loss and the immunodetection to different markers in neocortical tissue death in eigth patients with DRTLE. The neocortexes of five patients deceased due to non-neurological causes, paired in age and gender were evaluated as control tissue. Methods. The evaluation of neuronal loss was made by means of a stereological study and with immunohistochemical techniques with the synaptophysin marker. Immunopositivity to different apoptotic markers (annexin V, caspase 3 and 8, bcl-2 and p53) and detection of deoxyribonucleic acid (DNA) fragmentation (TUNEL) were analyzed and double labeling with synaptophysin was performed in every case. The results were evaluated with confocal microscope and analyzed with the Zeiss LSM 5 Image Browser Program, 2.80.1113 (Germany). Results. A statistically significant decrease in the total number of cells (p < 0.05) and the synaptophysin cells+ (p<0.01) in the neocortex (layer IV) of the patients with DRTLE when compared with the control tissue was found. No significant differences were found in the apoptotic markers bcl-2, p53, caspase 3 and 8 for any of the neocortex layers while there was a statistically significant increase in the number of TUNEL cells+ (p<0.05) and annexin V+ (p<0.05) in the neocortical layer IV of the patients. Conclusions. This group of evidence speaks in favor of the existence of an effect on the neuronal number in the neocortex layer IV that may be associated with noncaspase dependent apoptotic death process, without being able to rule out death by necrosis. Key words: Drug resistant temporal lobe epilepsy. Apoptosis. Necrosis. Neuronal loss. Neurología 2008;23(9):555-565.

Alteraciones inmunológicas en pacientes epilépticos asociadas a la localización del foco epileptogénico. Réplica / Immunological disorders in epileptic patients linked to the localisation of the epileptogenic focus. Reply

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Réplica. Alteraciones inmunológicas en pacientes epilépticos asociadas a la localización del foco epileptogénico / Reply. Immunological disorders in epileptic patients are associated to the epileptogenic focus localization

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[The effects of lesions in the compact part of the substantia nigra on glutamate and GABA release in the pedunculopontine nucleus]. / Efecto de la lesión de la sustancia negra pars compacta sobre la liberación de glutamato y GABA en el núcleo pedunculopontino.

INTRODUCTION: The pedunculopontine nucleus (PPN), co-localized with the mesencephalic locomotor region, has been proposed as a key structure in the physiopathology of Parkinson's disease. OBJECTIVES: The goal of the present study was to assess if the aminoacid neurotransmitter release in the PPN is modified by the degeneration of dopaminergic cells, from substantia nigra pars compacta in 6-hydroxidopamine (6-OHDA)-lesioned rats. In addition, it was studied the aminoacid neurotransmitter release in the PPN of rats with lesion of the subthalamic nucleus by quinolinic acid (QUIN) (100 nmol) intracerebral injection. MATERIALS AND METHODS: Rats were assigned to five groups: untreated rats (I) (n = 13), 6-OHDA lesion (II) (n = 11), 6-OHDA + QUIN lesion (III) (n = 9), sham-operated (IV) (n = 10), QUIN, STN (V) lesioned (n = 9). The extracellular concentrations of glutamic acid (GLU) and gamma-aminobutyric acid (GABA) were determined by brain microdialysis and high performance liquid chromatography (HPLC). RESULTS. GLU released in PPN from 6-OHDA lesioned rats (group II), was significantly increased in comparison with the others groups (F(4, 47) = 18.21, p < 0.001). GABA released shows significant differences between experimental groups (F(4, 45) = 12.75, p < 0.001). It was detected a higher valour (p < 0.05) in-group II. The groups III and IV exhibited intermeddle valour (p < 0.001) and groups I and IV (p < 0.001) showed the lower GABA extracellular concentrations. The infusion of artificial cerebrospinal fluid with higher potassium (100 mmol) induced an increase in the GLU and GABA released in all groups, which confirm the neuronal origin of the extracellular content. CONCLUSION: These results are in agreement with the current model of basal ganglia functioning and suggest the role of STN-PPN projection in the physiopathology of Parkinson's disease.

Efecto de la lesión de la sustancia negra parte compacta sobre la liberación de glutamato y GABA en el núcleo pedunculopontino / The effects of lesions in the compact part of the substantia nigra on glutamate and GABA release in the pedunculopontine nucleus

The pedunculopontine nucleus (PPN), co-localized with the mesencephalic locomotor region, has been proposed as a key structure in the physiopathology of Parkinson's disease. OBJECTIVES: The goal of the present study was to assess if the aminoacid neurotransmitter release in the PPN is modified by the degeneration of dopaminergic cells, from substantia nigra pars compacta in 6-hydroxidopamine (6-OHDA)-lesioned rats. In addition, it was studied the aminoacid neurotransmitter release in the PPN of rats with lesion of the subthalamic nucleus by quinolinic acid (QUIN) (100 nmol) intracerebral injection...(AU)

Efecto de la lesión de la sustancia negra pars compacta sobre la liberación de glutamato y GABA en el núcleo pedunculopontino / The effects of lesions in the compact part of the substantia nigra on glutamate and gaba release in the pedunculopontine nucleus

Introducción. El núcleo pedunculopontino (NPP), colocalizado con el área locomotora mesencefálica, se ha señalado como una estructura clave en la fisiopatología de la enfermedad de Parkinson. Objetivos. 1. Estudiar el efecto de la lesión de la sustancia negra pars compacta -por inyección de 6-hidroxidopamina (6-OHDA)- sobre la liberación de aminoácidos neurotransmisores en el NPP. 2. Estudiar el efecto de la lesión del núcleo subtalámico (NST), por inyección intracerebral de 100 nmol de ácido quinolínico (QUIN), sobre la liberación de aminoácidos neurotransmisores en el NPP. Materiales y métodos. Se organizaron cinco grupos experimentales: ratas sanas (I; n = 13), lesión con 6-OHDA (II; n = 11), lesión simultánea de 6-OHDA + QUIN (III; n = 9), falsa lesión de 6-OHDA (IV; n = 10), y lesión del NST con QUIN (V; n = 9). Las concentraciones extracelulares de ácido glutámico (GLU) y GABA se determinaron por medio de cromatografía líquida de alta resolución (HPLC) con detección fluorimétrica. Resultados. Se detectaron diferencias significativas en la liberación de GLU entre todos los grupos experimentales (F(4, 47) = 18,21, p < 0,001), con un aumento significativo de esta variable en el grupo II. La liberación de GABA en el NPP mostró diferencias significativas entre los grupos en estudio (F(4, 45) = 12,75, p < 0,001). Para esta variable se produjo una separación entre los grupos, con un aumento significativo (p < 0,05) en el grupo II, valores intermedios y significativamente diferentes para los grupos III y V (p < 0,001) y valores menores para los grupos I y IV. La infusión de una solución de líquido cefalorraquídeo artificial con mayor concentración de potasio (100 mmol) produjo un incremento en la liberación de los aminoácidos neurotransmisores en todos los grupos experimentales, lo cual confirma el origen neuronal del contenido extracelular estudiado. Conclusiones. Estos resultados concuerdan con el ‘modelo’ actual de funcionamiento de los ganglios basales y sugieren un papel importante a la proyección STN-NPP en la fisiopatología de la enfermedad de Parkinson

Introduction. The pedunculopontine nucleus (PPN), co-localized with the mesencephalic locomotor region, has been proposed as a key structure in the physiopathology of Parkinson’s disease. Objectives. The goal of the present study was to assess if the aminoacid neurotransmitter release in the PPN is modified by the degeneration of dopaminergic cells, from substantia nigra pars compacta in 6-hydroxidopamine (6-OHDA)-lesioned rats. In addition, it was studied the aminoacid neurotransmitter release in the PPN of rats with lesion of the subthalamic nucleus by quinolinic acid (QUIN) (100 nmol) intracerebral injection. Materials and methods. Rats were assigned to five groups: untreated rats (I) (n = 13), 6-OHDA lesion (II) (n = 11), 6-OHDA + QUIN lesion (III) (n = 9), sham-operated (IV) (n = 10), QUIN, STN (V) lesioned (n = 9). The extracellular concentrations of glutamic acid (GLU) and gamma-aminobutyric acid (GABA) were determined by brain microdialysis and high performance liquid chromatography (HPLC). Results. GLU released in PPN from 6-OHDA lesioned rats (group II), was significantly increased in comparison with the others groups (F(4, 47) = 18.21, p < 0.001). GABA released shows significant differences between experimental groups (F(4, 45) = 12.75, p < 0.001). It was detected a higher valour (p < 0.05) in-group II. The groups III and IV exhibited intermeddle valour (p < 0.001) and groups I and IV (p < 0.001) showed the lower GABA extracellular concentrations. The infusion of artificial cerebrospinal fluid with higher potassium (100 mmol) induced an increase in the GLU and GABA released in all groups, which confirm the neuronal origin of the extracellular content. Conclusion. These results are in agreement with the current model of basal ganglia functioning and suggest the role of STN-PPN projection in the physiopathology of Parkinson’s disease

[Stromal cell transplant in the 6-OHDA lesion model]. / Trasplante de células estromales en el modelo de lesión por 6-OHDA.

INTRODUCTION: A good deal of evidence currently exists to show that transplanting foetal mesencephalic tissue can produce symptomatic benefits both in patients and in disease models. Nevertheless, the technical and ethical difficulties involved in obtaining enough suitable foetal cerebral tissue have been a serious obstacle to its application. Stromal cells derived from bone marrow, due to their potential capacity to generate different types of cells, could be an ideal source of material for cell restoration in neurodegenerative diseases. AIMS: Our aim was to evaluate the effect of transplanting stromal cells derived from bone marrow on the behaviour of 6-OHDA rats, when they are inserted into the striatum. MATERIAL AND METHODS: In this study we used rats with a lesion in the substantia nigra induced by 6-hydroxydopamine, divided into several experimental groups. Rotary activity induced by D-amphetamine (5 mg/kg, intraperitoneally) was evaluated before and throughout the three months following the transplant in all the experimental groups, except in the group of healthy controls. Hemiparkinsonian rats received a total of 350 000 foetal ventral mesencephalic cells and 8 x 10(4) stromal cells/microL, which were implanted in the striatum. RESULTS AND CONCLUSIONS: Animals with stromal cells transplanted in the body of the striatum significantly reduced the number of turns induced by amphetamine (p < 0.05); yet this reduction was not greater than that induced by foetal mesencephalic cell transplants. We were also unable to demonstrate any significant improvement in the motor skills of the forelimbs.

Trasplante de células estromales en el modelo de lesión por 6-OHDA / Stromal cell transplant in the 6-OHDA lesion model

A good deal of evidence currently exists to show that transplanting foetal mesencephalic tissue can produce symptomatic benefits both in patients and in disease models. Nevertheless, the technical and ethical difficulties involved in obtaining enough suitable foetal cerebral tissue have been a serious obstacle to its application. Stromal cells derived from bone marrow, due to their potential capacity to generate different types of cells, could be an ideal source of material for cell restoration in neurodegenerative diseases. AIMS: Our aim was to evaluate the effect of transplanting stromal cells derived from bone marrow on the behaviour of 6-OHDA rats, when they are inserted into the striatum(AU)

Trasplante de células estromales en el modelo de lesión por 6-OHDA / Stromal cell transplant in the 6-OHDA lesion model

Introducción. En la actualidad, existe un cúmulo de evidencias de que el trasplante de tejido mesencefálico fetal puede producir un beneficio sintomático tanto en los pacientes con enfermedad de Parkinson como en los modelos de la enfermedad. Sin embargo, las dificultades técnicas y éticas en la obtención de tejido cerebral fetal apropiado y en cantidad suficiente ha dificultado su aplicación. Las células estromales derivadas de médula ósea, debido a su potencialidad para generar diferentes tipos de células, podrían ser una fuente ideal para la restauración celular en las enfermedades neurodegenerativas. Objetivo. Evaluar el efecto del trasplante de células estromales derivadas de médula ósea sobre la conducta de ratas con lesión por 6-OHDA, cuando se realiza en el estriado. Materiales y métodos. Se utilizaron ratas con lesión de la sustancia negra inducida por la 6-OHDA, divididas en varios grupos experimentales. La actividad rotatoria inducida por D-anfetamina (5 mg/kg intraperitonialmente) se evaluó antes y en los tres meses posteriores al trasplante en todos los grupos experimentales, excepto en el grupo de controles sanas. Las ratas hemiparkinsonianas recibieron un total de 350.000 células de mesencéfalo ventral fetal y 8 × 104 células estromales/µL, las cuales se implantaron en el estriado. Resultados y conclusiones. Los animales con trasplante de células estromales en el cuerpo estriado redujeron significativamente el número de vueltas inducidas por anfetamina (p < 0,05); sin embargo, esta reducción no fue mayor que la inducida por los trasplantes de células mesencefálicas fetales. Por otro lado, no fue posible demostrar una mejoría significativa de las habilidades motoras de las extremidades anteriores (AU)

Introduction. A good deal of evidence currently exists to show that transplanting foetal mesencephalic tissue can produce symptomatic benefits both in patients and in disease models. Nevertheless, the technical and ethical difficulties involved in obtaining enough suitable foetal cerebral tissue have been a serious obstacle to its application. Stromal cells derived from bone marrow, due to their potential capacity to generate different types of cells, could be an ideal source of material for cell restoration in neurodegenerative diseases. Aims. Our aim was to evaluate the effect of transplanting stromal cells derived from bone marrow on the behaviour of 6-OHDA rats, when they are inserted into the striatum. Materials and methods. In this study we used rats with a lesion in the substantia nigra induced by 6-hydroxydopamine, divided into several experimental groups. Rotary activity induced by D-amphetamine (5 mg/kg, intraperitoneally) was evaluated before and throughout the three months following the transplant in all the experimental groups, except in the group of healthy controls. Hemiparkinsonian rats received a total of 350,000 foetal ventral mesencephalic cells and 8 × 104 stromal cells/µL, which were implanted in the striatum. Results and conclusions. Animals with stromal cells transplanted in the body of the striatum significantly reduced the number of turns induced by amphetamine (p < 0.05); yet this reduction was not greater than that induced by foetal mesencephalic cell transplants. We were also unable to demonstrate any significant improvement in the motor skills of the forelimbs (AU)

[Immunological disorders in epileptic patients are associated to the epileptogenic focus localization]. / Alteraciones inmunológicas en pacientes epilépticos asociadas a la localización del foco epileptogénico.

OBJECTIVE: Clinical and experimental data support the role of immune mechanisms in the pathogeny of epilepsy. The purpose of this work was to study the immunological aspects in 30 epileptic patients with complex partial crisis resistant to antiepileptic drugs. PATIENTS AND METHODS: The patients were evaluated by EEG-Video and they were grouped attending to epileptogenic focus localization in: temporals (n = 16), lateralized (n = 6) and extratemporals (n = 4). We also studied a group with psychogenic epilepsy (n = 4), this group was diagnosed after EEG-video evaluation. The following immunological evaluations has been carried out: levels of serum immunoglobulins (IgG, IgM e IgA) by radial immunodiffusion test and lymphocytic subpopulations using immunocytochemical methods. We measured the percent of T and B lymphocytes (CD3 and CD20), helper/inductor lymphocyte T (CD4), suppressor/cytotoxic (CD8), interleukine-2 receptor (CD25) and human leukocyte antigen (HLA-DR). RESULTS: The results show a significant increase of CD8+ lymphocytes (p < 0.05) and in the activation markers (CD25+ and HLA-DR+ cells). The evaluation of immunological parameters applied to different group of epileptogenic focus localization shown that the increase of CD8+ lymphocytes is limited to temporal and lateralized patients (p < 0.01). The patients with extratemporal localization of focus and the psychogenic cases shown normal values for the evaluated immunological lymphocyte markers. We did not find a deficit in the humoral immunological aspects. CONCLUSIONS: Taking into account that patients diagnosed as psychogenic received an antiepileptic drug treatment identical to that of the other group, the observed immunological changes might be related with the patogeny of certain epilepsy variants associated with the focus localization and not with the medication.

Alteraciones inmunológicas en pacientes epilépticos asociadas a la localización del foco epileptogénico / Immunological disorders in epileptic patients are associated to the epileptogenic focus localization

Objetivo. Datos clínicos y experimentales evidencian el papel del sistema inmune en la patogenia de la epilepsia. El propósito de este trabajo es mostrar los resultados de los estudios inmunológicos realizados a 30 pacientes epilépticos con crisis parciales complejas refractarias a tratamiento médico, evaluados por vídeo-EEG. Pacientes y métodos. Los pacientes se agruparon de acuerdo con la localización del foco epileptogénico en: temporales (n = 16), lateralizados (n = 6) y extratemporales (n = 4). Se estudiaron, además, pacientes (n = 4) diagnosticados según la evaluación por vídeo-EEG como epilepsia psicógena. Se determinaron los niveles de inmunoglobulinas (IgG, IgM e IgA) por inmunodifusión radial y se cuantificaron por inmunocitoquímica los linfocitos T y B (CD3 y CD20), así como los marcadores linfocitarios: CD4, CD8, CD25 y HLA-DR. Resultados. Se evidenció un aumento significativo en el porcentaje de linfocitos T CD8+ (supresores/citotóxicos, p < 0,05) y de los marcadores de activación CD25 (células receptor IL-2) y HLA-DR (antígeno leucocitario humano DR). La evaluación de los parámetros inmunológicos en los diferentes grupos de localización del foco epileptogénico mostró que el aumento significativo de los linfocitos CD8+ se limita a los casos temporales y lateralizados (p < 0,01). Los pacientes con localización extratemporal y los casos psicógenos mostraron valores normales para todos los marcadores evaluados; este último grupo recibía el mismo tratamiento médico que el resto de los pacientes. Conclusiones. Estos resultados evidencian que existen alteraciones del sistema inmune en los pacientes epilépticos con crisis parciales complejas no asociadas al tratamiento antiepiléptico; las mismas pueden ser factores relevantes en la patogenia de la epilepsia y guardan relación con la localización del foco epileptogénico (AU)

Objective. Clinical and experimental data support the role of immune mechanisms in the pathogeny of epilepsy. The purpose of this work was to study the immunological aspects in 30 epileptic patients with complex partial crisis resistant to antiepileptic drugs. Patients and methods. The patients were evaluated by EEG-Video and they were grouped attending to epileptogenic focus localization in: temporals (n = 16), lateralized (n = 6) and extratemporals (n = 4). We also studied a group with psychogenic epilepsy (n = 4), this group was diagnosed after EEG-video evaluation. The following immunological evaluations has been carried out: levels of serum immunoglobulins (IgG, IgM e IgA) by radial immunodiffusion test and lymphocytic subpopulations using immunocytochemical methods. We measured the percent of T and B lymphocytes (CD3 and CD20), helper/inductor lymphocyte T (CD4), suppresor/cytotoxic (CD8), interleukine-2 receptor (CD25) and human leukocyte antigen (HLA-DR). Results. The results show a significant increase of CD8+ lymphocytes (p < 0.05) and in the activation markers (CD25+ and HLA-DR+ cells). The evaluation of immunological parameters applied to different group of epileptogenic focus localization shown that the increase of CD8+ lymphocytes is limited to temporal and lateralized patients (p < 0.01). The patients with extratemporal localization of focus and the psychogenic cases shown normal values for the evaluated immunological lymphocyte markers. We did not find a deficit in the humoral immunological aspects. Conclusions. Taking into account that patients diagnosed as psyhcogenic received an antiepileptic drug treatment identical to that of the other group, the observed immunological changes might be related with the patogeny of certain epilepsy variants associated with the focus localization and not with the medication (AU)

Alteraciones inmunológicas en pacientes epilépticos asociadas a la localización del foco epileptogénico

Datos clínicos y experimentales evidencian el papel del sistema inmune en la patogenia de la epilepsia. El propósito de este trabajo es mostrar los resultados de los estudios inmunológicos realizados a 30 pacientes epilépticos con crisis parciales complejas refractarias a tratamiento médico, evaluados por vídeo-EEG. Pacientes y métodos. Los pacientes se agruparon de acuerdo con la localización del foco epileptogénico en: temporales (n = 16), lateralizados (n = 6) y extratemporales (n = 4). Se estudiaron, además, pacientes (n = 4) diagnosticados según la evaluación por vídeo-EEG como epilepsia psicógena. Se determinaron los niveles de inmunoglobulinas (IgG, IgM e IgA) por inmunodifusión radial y se cuantificaron por inmunocitoquímica los linfocitos T y B (CD3 y CD20), así como los marcadores linfocitarios: CD4, CD8, CD25 y HLA-DR. Resultados. Se evidenció un aumento significativo en el porcentaje de linfocitos T CD8+ (supresores/citotóxicos, p < 0,05) y de los marcadores de activación CD25 (células receptor IL-2) y HLA-DR (antígeno leucocitario humano DR). La evaluación de los parámetros inmunológicos en los diferentes grupos de localización del foco epileptogénico mostró que el aumento significativo de los linfocitos CD8+ se limita a los casos temporales y lateralizados (p < 0,01). Los pacientes con localización extratemporal y los casos psicógenos mostraron valores normales para todos los marcadores evaluados; este último grupo recibía el mismo tratamiento médico que el resto de los pacientes. Conclusiones. Estos resultados evidencian que existen alteraciones del sistema inmune en los pacientes epilépticos con crisis parciales complejas no asociadas al tratamiento antiepiléptico; las mismas pueden ser factores relevantes en la patogenia de la epilepsia y guardan relación con la localización del foco epileptogénico(AU)

[Lesions in the pars compacta substantiae nigra and the subthalamic nucleus modify the density of muscarinic receptors in different nuclei of the basal ganglia]. / La lesión de la sustancia negra pars compacta y del núcleo subtalámico modifica la densidad de receptores muscarínicos en distintos núcleos de los ganglios basales.

INTRODUCTION: Several studies that has focused to the dopaminergic transmission in the basal ganglia in parkinsonian condition, but only a few article has taking into account the imbalance between dopaminergic and cholinergic transmission. OBJECTIVE: To evaluate the muscarinic cholinergic receptors density in SNc and PPN in the 6-OHDA model. MATERIALS AND METHODS: Were organized five experimental groups in correspondence to the place of the lesion: I. Non treated rats, II. 6-OHDA lesion in SNc, III. 6-OHDA lesion in SNc + quinolinic acid lesion in NST, IV. Sham operated rats, V. Quinolinic acid in STN. Were obtained coronal sections of 20 microm thickness of SNc and PPN from rats and in these sections was evaluated the muscarinic receptors density through autoradiographic technique with [3H]quinuclidinylbenzilate (QNB) (1.23 nM). The muscarinic antagonist atropine (1 microM) was utilized as non-specific union. The density was evaluated in both hemispheres and the density optical was converted in fentomolas/mg of tissue with base to values obtained from tritium standards. RESULTS: Significant diminution of the muscarinic receptors density was found in the SNc ipsilateral to the 6-OHDA lesion from experimental groups II (t=2.76; p<0.05) and III (t=4.06; p<0.05). In the group V, was seen a significant increase of muscarinic receptor density in the SNc ipsilateral to the 6-OHDA lesion. The comparison between experimental groups evidenced significant differences among them (F=13.13; p<0.001) with a significant decrease in the density from SNc of groups II and III and significant increase in the density from SNc of group V in comparison of the others groups. In relation to PPN, muscarinic receptors density from right PPN ipsilateral to the 6-OHDA lesion, shown significant differences (F=3.93; p<0.01) between the experimental groups with a significant increase of this variable in the group II. CONCLUSIONS: These results signal a modification of cholinergic activity after 6-OHDA lesion. The changes in the muscarinic receptors populations located in SNc and PPN could be part of different compensatory mechanisms to attempt ameliorate the imbalance between dopaminergic and cholinergic transmission that it was installed after denervation of nigrostriatal forebrain bundle. The excitotoxic lesion of STN impose a new adjust mechanism for cell from PPN, which could be expressed in the changes of muscarinic cholinergic receptors population at the level of SNc.

La lesión de la sustancia negra pars compacta y del núcleo subtalámico modifica la densidad de receptores muscarínicos en distintos núcleos de los ganglios basales / Lesions in the pars compacta substantiae nigrae and the subthalamic nucleus modify the density of muscarinic receptors in different nuclei of the basal ganglia

Introducción. Numerosos estudios han abordado el papel de la neurotransmisión dopaminérgica en los ganglios basales en condiciones de parkinsonismo, pero pocos se han encaminado hacia el desequilibrio entre la trasmisión dopaminérgica y colinérgica. Objetivo. Evaluar la densidad de receptores colinérgicos muscarínicos en sustancia negra pars compacta (SNc) y núcleo pedunculopontino (NPP) en el modelo de 6-OHDA. Materiales y métodos. Se organizaron cinco grupos experimentales según la lesión de SNcyNST: 1. Animales sanos; 2. Ratas lesionadas con 6-OHDA; 3. Ratas con lesión simultánea de SNcyNST; 4. Ratas Sham del modelo de 6-OHDA; 5. Ratas con lesión de NST. Se obtuvieron cortes de 20 µm de grosor de SNc y NPP de ratas, en los cuales se evaluó la densidad de receptores colinérgicos muscarínicos por autorradiografía con [3H]quinuclidinilbencilato (QNB) (1,23 nM). Como unión no específica se usó el antagonista muscarínico atropina (1 µM). Se realizaron lecturas en los dos hemisferios y la densidad óptica se convirtió en fentomolas por mg de tejido con base en los valores obtenidos de los estándares de tritio. Resultados. En los grupos 2 (t = 2,76; p < 0,05) y 3 (t = 4,06; p < 0,05) se evidenció una disminución significativa de la densidad de receptores muscarínicos en la SNc ipsilateral a la lesión de 6-OHDA. El grupo 5 mostró un aumento significativo de la densidad de receptores muscarínicos en la SNc lesionada con 6-OHDA (t = 2,69; p < 0,05). La comparación entre grupos experimentales arrojó diferencias significativas entre éstos (F=13,13;p<0,001), con una disminución en los grupos 2 y 3 y un aumento significativo en el grupo 5, en relación con los restantes grupos. La densidad de receptores muscarínicos para el NPP derecho ipsilateral a la lesión de SNc mostró diferencias significativas entre los grupos experimentales (F=3,93;p<0,01), con un aumento significativo de esta variable en el grupo 2. Conclusiones. Estos resultados apuntan hacia una modificación de la actividad colinérgica posterior a la denervación de la SNc por inyección de 6-OHDA. Los cambios en las poblaciones de receptores muscarínicos distribuidos en SNc y NPP pueden ser parte de distintos mecanismos compensatorios que intentan atenuar el desequilibrio entre las transmisiones dopaminérgica y colinérgica, que se instala después de la degeneración de la vía negroestriatal. La lesión excitotóxica de lNST impone un nuevo mecanismo de ajuste a las células del NPP, que pudiera expresarse en los cambios en las poblaciones de receptores colinérgicos de la SNc (AU)

Introduction. Several studies that has focused to the dopaminergic transmission in the basal ganglia in parkinsonian condition, but only a few article has taking into account the imbalance between dopaminergic and cholinergic transmission. Objective. To evaluate the muscarinic cholinergic receptors density in SNc and PPN in the 6-OHDA model. Materials and methods. Were organized five experimental groups in correspondence to the place of the lesion: I. Non treated rats, II. 6-OHDA lesion in SNc, III. 6-OHDA lesion in SNc + quinolinic acid lesion in NST, IV. Sham operated rats, V. Quinolinic acid in STN. Were obtained coronal sections of 20 µm thickness of SNc and PPN from rats and in these sections was evaluated the muscarinic receptors density through autoradiographic technique with [3H]quinuclidinylbenzilate (QNB) (1.23 nM). The muscarinic antagonist atropine (1 µM) was utilized as non-specific union. The density was evaluated in both hemispheres and the density optical was converted in fentomolas/mg of tissue with base to values obtained from tritium standards. Results. Significant diminution of the muscarinic receptors density was found in the SNc ipsilateral to the 6-OHDA lesion from experimental groups II (t = 2.76; p < 0.05) and III (t = 4.06; p < 0.05). In the group V, was seen a significant increase of muscarinic receptor density in the SNc ipsilateral to the 6-OHDA lesion. The comparison between experimental groups evidenced significant differences among them (F = 13.13; p < 0.001) with a significant decrease in the density from SNc of groups II and III and significant increase in the density from SNc of group V in comparison of the others groups. In relation to PPN, muscarinic receptors density from right PPN ipsilateral to the 6-OHDA lesion, shown significant differences (F = 3.93; p < 0.01) between the experimental groups with a significant increase of this variable in the group II. Conclusions. These results signal a modification of cholinergic activity after 6-OHDA lesion. The changes in the muscarinic receptors populations located in SNc and PPN could be part of different compensatory mechanisms to attempt ameliorate the imbalance between dopaminergic and cholinergic transmission that it was installed after denervation of nigrostriatal forebrain bundle. The excitotoxic lesion of STN impose a new adjust mechanism for cell from PPN, which could be expressed in the changes of muscarinic cholinergic receptors population at the level of SNc (AU)

[The pedunculopontine nucleus. A structure involved in motor and emotional processing]. / Núcleo pedunculopontino. Una estructura involucrada en el procesamiento motor y emocional.

INTRODUCTION: There is currently a growing interest for conducting studies into the electrical and neurochemical activity of the pedunculopontine nucleus (PPN) due to the privileged position occupied by this structure in the flow of information to and from the cortex. This nucleus acts as a relay, not only for the motor information that is processed in the basal ganglia but also for information of an emotional type, whose main centre is the nucleus accumbens. It is also strongly linked with the aspects that determine the mechanisms governing addiction to certain drugs. DEVELOPMENT: We conduct a detailed analysis of the main findings from studies of the role played by the PPN in the physiopathology of Parkinsonism, namely the study of metabolic activity, immunohistochemical studies with different tracers, electrophysiological studies that have confirmed the immunohistochemical observations, as well as deep electrical stimulation carried out in non human primates. Furthermore, we also examine the part played by this structure in the processing of emotional information associated with different learning tasks. CONCLUSIONS: Overall, the authors grant the PPN a privileged position in the physiopathology of the axial disorders related to Parkinson s disease; its most important afference, stemming from the subthalamic nucleus, appears to play a key role in the understanding of the part played by the PPN in Parkinsonism.

Núcleo pedunculopontino. Una estructura involucrada en el procesamiento motor y emocional / The pedunculopontine nucleus. A structure involved in motor and emotional processiong

Introducción. Existe en la actualidad un interés creciente por abordar el estudio de la actividad eléctrica y neuroquímica del núcleo pedunculopontino (NPP), debido a la posición privilegiada de esta estructura en el flujo de información que procede de la corteza y regresa a ella. Este núcleo sirve de relevo no sólo a la información motora que se procesa en los ganglios basales, sino también a la información de tipo emocional cuyo principal centro es el núcleo accumbens y está estrechamente relacionado con los mecanismos de adicción a determinados fármacos. Desarrollo. Se realiza un análisis detallado de los principales resultados sobre la función que desempeña el NPP en la fisiopatología del parkinsonismo, a saber: estudio de su actividad metabólica, estudios inmunohistoquímicos con diferentes trazadores, estudios electrofisiológicos-que han confirmado las observaciones inmunohistoquímicas-, así como estimulación eléctrica profunda practicada en primates. Igualmente, se aborda la participación de esta estructura en el procesamiento de información emocional asociada a distintas tareas de aprendizaje. Conclusiones. En general, los autores confieren al NPP una función privilegiada en la fisiopatología de los trastornos axiales relacionados con la enfermedad de Parkinson; su aferencia más importante, procedente del núcleo subtalámico, parece ser una pieza clave para entender la participación del NPP en el parkinsonismo (AU)

[Effects of simultaneous transplant of foetal mesencephalic cells in the striatum and the subthalamic nucleus of hemiparkinsonian rats]. / Efectos del trasplante simultáneo de células mesencefálicas fetales en el estriado y el núcleo subtalámico de ratas hemiparkinsonianas.

INTRODUCTION: The main strategy followed in neural transplants as a method of treatment for Parkinson s disease, both experimental and clinical, has been to introduce foetal mesencephalic cells into the target area: the striatum. However, when the dopaminergic cells in the substantia nigra degenerate, not only is the dopaminergic innervation of the striatum affected but also other nuclei: globus pallidus, substantia nigra, substantia nigra pars reticulata and subthalamic nucleus. A series of data from pharmacological and physiological studies offer strong evidence that the dopamine released in these nuclei may play an important role in regulating the output nuclei of the basal ganglia. AIM: To evaluate the effect of transplanting foetal mesencephalic cells on the behaviour of 6 OH DA rats when introduced into the striatum and the subthalamic nucleus. MATERIALS AND METHODS: 6 OH DA was used to induce lesions in the substantia nigra of rats, which were divided into several experimental groups. The rotating activity induced by D amphetamine (5 mg/kg, intraperitoneally) and apomorphine (0.05 mg/kg, subcutaneously) was evaluated before and three months after the transplant in all the experimental groups, except in the control group of healthy rats. The hemiparkinsonian rats received a total of 350,000 foetal ventral mesencephalic cells, which were implanted within small deposits in the striatum (8) and in the subthalamic nucleus (4). RESULTS AND CONCLUSIONS: Rotation induced by both drugs was significantly lower (p= 0.05) in animals that had had dopaminergic cells transplanted into the striatum body. No significant improvement in this behaviour was to be found when transplants were limited to just the subthalamus or, simultaneously, also to the striatum. A significant increase in rotating behaviour induced by apomorphine was observed in the group which received a transplant in just the subthalamus.

Efectos del trasplante simultáneo de células mesencefálicas fetales en el estriado y el núcleo subtalámico de ratas hemiparkinsonianas / Effects of simultaneous transplant of foetal mesencephalic cells in the striatum and the subthalamic nucleus of hemiparkinsonian rats

Introducción. La principal estrategia de trasplante neural como tratamiento de la enfermedad de Parkinson, tanto experimental como clínico, ha sido colocar las células mesencefálicas fetales en su principal blanco: el estriado. Sin embargo, cuando las células dopaminérgicas de la sustancia negra degeneran, no sólo se afecta la inervación dopaminérgica del estriado; por el contrario, la inervación de otros núcleos, como el globo pálido, sustancia negra parte reticulada y núcleo subtalámico, también se afectan. Una serie de datos provenientes de estudios farmacológicos y fisiológicos proveen de fuertes evidencias acerca de que la dopamina liberada en estos núcleos puede desempeñar un papel importante en la regulación de los núcleos de salida de los ganglios basales. Objetivo. El objetivo principal de este estudio fue evaluar el efecto del trasplante de células mesencefálicas fetales sobre la conducta de ratas-6-OH-DA, cuando el mismo se coloca en el estriado y el núcleo subtalámico. Materiales y métodos. Se utilizaron ratas con lesión de la sustancia negra inducida por la 6-OHDA, divididas en varios grupos experimentales. La actividad rotatoria inducida por D-anfetamina (5 mg/kg, intraperitonealmente) y apomorfina (0,05 mg/kg, subcutáneamente) se evaluó antes y en los tres meses posteriores al trasplante en todos los grupos experimentales, excepto en el grupo de controles sanos. Las ratas hemiparkinsonianas recibieron un total de 350.000 células de mesencéfalo ventral fetal, que se implantaron en pequeños depósitos en el estriado (8) y en el núcleo subtalámico (4). Resultados y conclusiones. Los animales con trasplante de células dopaminérgicas en el cuerpo estriado redujeron significativamente el número de vueltas inducido por ambas drogas (p= 0,05). No fue posible demostrar mejoría significativa de estas conductas cuando los trasplantes se colocaron sólo en el subtálamo o en este núcleo, simultáneamente al estriado. Se observó un incremento significativo en la conducta de giro inducida por apomorfina en el grupo con trasplante aislado en subtálamo (AU)