[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.

[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.

[Subthalamic nucleus targeting and spatial variability]. / Localización bilateral y simetría del núcleo subtalámico.

AIM: The effectiveness of anatomic localization of the subthalamic nucleus (EAL) was assessed and the mapping method is described here. The symmetry of contralateral nuclei (SCN) was analyzed on 11 parkinsonian patients submitted to bilateral subthalamotomy with ablative lesioning. PATIENTS AND METHODS: To assess EAL the percentage so much of first trajectory (p1) as the total of trajectories (pt) that hit the target and the rest of subthalamic nucleus average distance (d) was calculated. The anatomic localization error (epsilon) is determined as a difference between first trajectory coordinates with those of medial determined nucleus point, through electrophysiological data as to the statistical significance of this error. SCN is analyzed by contrasting equality hypothesis at the nucleus maximum height alongside a trajectory, average electrophysiological position center and spatial distribution of all intranuclear recordings found in each hemisphere in all patients. RESULTS: The pi, pt and d obtained values were 86.36%, 86.13% and 1.41 +/- 1.01 mm respectively. The epsilon value was greater in anteroposterior direction of 1.11 +/- 0.83 mm without statistical significance. The average number of recorded trajectories for the first procedure was 6.45 and 6 for the second. The asymmetry of contralateral nucleus was not significant. CONCLUSIONS: An indirect method with CT brain images and a new electrophysiological mapping method with a multiunitary recording for first and second nucleus is safe enough and it yields a high effectiveness in anatomofunctional nucleus localization. The nucleus of a same patient are symmetrical. There is little space variability among patient non related to the differences in the intercommissural distance.

[Database application for information on post-surgical evolution after functional neurosurgery]. / Programa de base de datos sobre evolución posquirúrgica de la neurocirugía funcional.

INTRODUCTION: A series of quantitative scales have been established internationally to evaluate the functional state of patients affected by movement disorders, such as Parkinson s disease. The values of these parameters offered by each patient, measured at different moments during his or her illness, allow us to conduct studies into their evolution as well as perform statistical studies about the casuistics. AIM. To provide a tool that enables us to study this vast amount of material in an efficient, sure and, above all, automated manner. Materials and methods. We selected the most interesting variables from the international protocols. We also designed and developed a database application for use under the Windows environment using Delphi 3.0 language and compiler and Structured Query Language. RESULTS: We designed, developed and validated a database system so as to be able to handle automatically the information on the clinical evolution of patients who had undergone functional neurosurgery. This system not only enables us to collect all relevant pre and post surgical information but also allows fast searches and selection, data processing using descriptive statistical techniques and the exportation of the data in a standard format. The system, which also allows final double blind clinical evaluation of each patient to be performed, has been used successfully in the Movement Disorders Clinic at the CIREN for over three years. CONCLUSIONS: This system allows for a considerable saving in the amount of time and effort needed for the post surgical evolution of patients, while also increasing the reliability of the results obtained.

[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.

[Contribution of thalamic somatosensory evoked potentials to stereotaxic thalamometry]. / Contribución de los potenciales somatosensoriales talámicos a la talamotomía estereotáxica.

INTRODUCTION: In order to use short latency somatosensory thalamic evoked potentials (PES) to locate therapeutic targets in functional surgery, thalamic PES were recorded during stereotactic thalamotomy in 25 patients with Parkinson's disease, using a concentric bipolar semi-micro-electrode, 4 mm in diameter. In the 72 trajectories planned. 628 registers were made, obtaining 314 PES in 55 trajectories. These recordings were divided into 5 groups, according to the electrical variables evaluated in each case (absolute latency, inter-peak latency, absolute amplitude and number of phases). MATERIAL AND METHODS: The electrophysiological characteristics of the PES groups obtained, and the spatial representation of these in a tridimensional system of coordinates, is shown. We analyze the sequence of the groups of potentials in each of the trajectories followed. CONCLUSIONS: We consider that the limit between adjacent nuclear edges, ventral intermediate (Vim)-ventro-caudal (Vc), may be represented by the transition of potentials in group 1 to potentials in group 4 and/or potentials of group 3 to those of group 2. This study shows that thalamic PES are useful for locating targets during stereotactic thalamotomy.

Contribución de los potenciales somatosensoriales talámicos a la talamotomía estereotáxica / Contribution of the thalamic somatosensory evoked potentials to stereotactic thalamotomy

Introducción. En un esfuerzo por utilizar los potenciales evocados somatosensoriales (PES) talámicos de corta latencia, como localizadores de blancos terapéuticos en la cirugía funcional, se registraron PES talámicos durante la talamotomía estereotáxica de 25 pacientes parkinsonianos, utilizando un semimicroelectrodo bipolar concéntrico de 0,4 mm de diámetro. A lo largo de las 72 trayectorias planificadas, se realizaron 628 registros obteniéndose 314 PES en 55 trayectorias. Estos registros se dividieron en cinco grupos, atendiendo a las variables eléctricas evaluadas para cada uno de ellos (latencia absoluta, latencia interpico, amplitud absoluta y número de fases). Material y métodos. Se muestra la caracterización electrofisiológica de los grupos de PES obtenidos, y la representación espacial de los mismos en un sistema de coordenadas tridimensional. Analizamos la secuencia de los grupos de potenciales en cada una de las trayectorias realizadas. Conclusiones. Planteamos que el límite entre bordes nucleares adyacentes ventral intermedio (Vim)-ventrocaudal (Vc) puede estar representado por la transición de potenciales del grupo 1 a potenciales del grupo 4 y/o de potenciales del grupo 3 a los del grupo 2. Con este estudio se demuestra la utilidad de los PES talámicos en la localización de los blancos durante la talamotomía estereotáxica

[Investigation of corticospinal dysfunction in multiple sclerosis and motoneuron diseases using motor evoked potentials]. / Disfunción corticospinal en la esclerosis múltiple y en las enfermedades de la neurona motora investigada mediante potenciales evocados motores.

INTRODUCTION: The introduction of motor evoked potentials (MEP) into neurological practice has been very useful in the study of motor disorders, especially in patients with motor neurone diseases (MND) and multiple sclerosis (MS). MATERIAL AND METHODS: Forty patients with MS, twenty with MND and sixty-four apparently normal control were studied, to evaluate the use of MEP in such patients. Bilateral recordings were made from the abductor pollicis brevis and tibialis anterior. The variables studied were: cortical latency, radicular latency, central conduction time, motor excitation threshold coefficients of amplitude, duration and number of phases. RESULTS: There were significant differences in most variables when the control group and the patients were compared, and also between the two subgroups of patients (Wilk's lambda = 0.4197; p < 0.05). CA analysis significantly increased the sensitivity of the study (90.4%) with respect to analysis of latencies and central conduction times (70.4%). When analysis of the coefficients of duration and of phases was included, specificity increased by approximately 30% in both groups of patients. CONCLUSIONS: The great sensitivity of MEP as a neurophysiological diagnostic tool in investigation of corticospinal bundle lesions was demonstrated.

[Automatic anatomic-physiologic correspondence of deep structures of the central nervous system in stereotaxic functional neurosurgery]. / Automatización de la correlación anatomofisiológica de las estructuras profundas del sistema nervioso central en la neurocirugía funcional estereotáxica.

This work describes in detail the graphic facilities of a neurosurgical deep recording system for the anatomic-physiologic analysis of central nervous system deep structures in stereotaxic function neurosurgery guided by deep semi-microrecordings of the brain, as developed by the International Center of Neurologic Restoration in Cuba. This system for digitization of electrical activity in the brain uses an IBM-compatible 80386/80486 microprocessor in place of analog equipment for the visualization and recording of signals, thereby providing easier manipulation of recorded data and greater flexibility of analysis. The system automatically integrates each pulse recorded and quantifies its average amplitude. For each brain region explored, the behavior of the integrated activity recorded can be displayed on the corresponding sagittal view from the cerebral atlas of Schaltenbrand-Wahren, and then automatically scaled to the anatomic dimensions of each patient. The picture, with its different options, Facilitates analysis of anatomic correspondence of deep electrophysiologic signals so the various structures, nuclei and specific neuronal groups can be precisely located in the patient's brain. To date the system has been used successfully in over 110 neurosurgical procedures ventral intermedios (vim)-thalamotomy, pallidotomy, subthalotomy and neurotransplantation, providing more certain location of lesions or grafting sites for managing symptoms in Parkinson's disease and other movement disorders.

Automatización de la correlación anatomofisiológica de las estructuras profundas del sistema nervioso central en la neurocirugía funcional estereotóxica / Automatic anatomic-physiologic correspondence of deep structures of the central nervous system in stereotaxic functional neurosurgery

Este trabajo describe en detalle las facilidades gráficas que brinda el sistema de programas NDRS (Neurosurgical Deep Recording System) para el análisis anatomofisiológico de las estructuras profundas del sistema nervioso central en la neurocirugía funcional estereotóxica guiada por semimicrorregistros profundos del cerebro, desarrollado en el Centro Internacional de Restauración Neurológica de Cuba. Este sistema de registro y procesamiento digital de la actividad eléctrica cerebral, además de permitir la sustitución con un microordenador personal 80386/80486 IBM compatible, del equipamiento electrónico de procesamiento analógico, visualización, y grabación de las señales, brinda una mayor facilidad para la manipulación de la información registrada y una mayor flexibilidad para la implementación de diferentes tipos de análisis de las señales. El sistema, como una de sus posibilidades, realiza automáticamente un proceso de integración de cada señal registrada, como cuantificación de su amplitud general. El comportamiento de esta actividad integrada puede ser mostrado a lo largo de cada trayectoria explorada dentro del cerebro, sobre la correspondiente vista sagital del atlas cerebral de Schaltenbrand-Wahren, después de una escala automática del mismo según las dimensiones automáticas de cada paciente. Este gráfico, con sus diferentes opciones, facilita el análisis de la correlaciøn anatómica de los registros electrofisiológicos profundos realizados para localizar la ubicación exacta, dentro del cerebro de cada paciente, de sus diferentes estructuras, núcleos y grupos neuronales específicos. Hasta el presente, este sistema ha sido utilizado con éxito en más de 110 intervenciones neuroquirúrgicas de núcleo ventral intermedio-talamotomías, palidotomías, subtalamotomías y neurotrasplantes, contribuyendo a aumentar la seguridad en la correcta selección de los lugares de lesión o implante para el control de los diferentes síntomas de la enfermedad de Parkinson y otros movimientos anormale

Disfunción corticospinal en la esclerosis múltiple y en las enfermedades de la neurona motora investigada mediante potenciales evocados motores / Corticospinal dysfunction in Multiple Sclerosis and in the diseases of the motor neuron investigated by motor evoked potentials

Introducción. La introducción de los potenciales evocados motores (PEM) en la práctica neurológica ha sido de gran importancia para el estudio de los trastornos motores, especialmente en pacientes con enfermedades de la neurona motora (ENM) y esclerosis múltiple (EM). Material y métodos. Con el objetivo de evaluar la utilidad clínica de los PEM en estos pacientes se realizó un estudio de 40 pacientes con diagnóstico de EM, 20 con ENM y un grupo control constituido por 64 sujetos supuestamente sanos. Se efectuaron registros sobre músculos abductor breve del pulgar y tibial anterior, bilateralmente. Fueron evaluadas las variables: latencia cortical, latencia radicular, tiempo de conducción central, umbral de excitación motor, cociente de amplitud, de duración y de número de fases. Resultados. Se encontraron diferencias significativas entre los valores observados en el grupo control y los pacientes, así como entre los dos subgrupos de pacientes (Lambda de Wilk=0,4197; p<0,05) en gran parte de las variables evaluadas. El análisis del CA incrementó significativamente la sensibilidad del estudio (90,4 por ciento) respecto al análisis de latencias y tiempo de conducción central per se (70,4 por ciento); mientras que la inclusión del análisis de los cocientes de duración y de fases incrementó la especificidad en un 30 por ciento aproximadamente para cada grupo de pacientes. Conclusiones. Se demostró la alta sensibilidad de los PEM como herramienta de diagnóstico neurofisiológico en la investigación de las lesiones del haz corticospinal

Potenciales corticales relacionados a movimientos en pacientes parkinsonianos sometidos a tratamiento quirúrgico neurorrestaurativo / Movement-related cortical potentials in parkinsonian patients with neurosurgical treatment

Uno de los componentes de los potenciales corticales relacionados con el movimiento, el Bereitschaft Potential (BP), se piensa que refleja la actividad preparatoria en las áreas corticales y subcorticales previas al movimiento voluntario. Estudios anatómicos han demostrado que el "output" palidal se dirige desde el tálamo al área motora suplementaria y al córtex premotor. Contrariamente el área premotora suplementaria envía un "input" hacia el pálido vía el estriado formando un "loop" anatómico entre las áreas motoras corticales y los ganglios basales. Hemos estudiado el BP en 13 pacientes parkinsonianos que fueron sometidos a diversos tratamientos neuroquirúrgicos (talamotomía, palidotomía y trasplante de tejido fetal) una semana antes y 6-8 meses después del procedimiento. Las mayores diferencias fueron observadas en el grupo de talamotomía, en relación al área entre el comienzo del BP y los 800 ms previos a la iniciación del movimiento. También observamos una correlación significativa entre esta área (800-200 ms antes del comienzo del movimiento) y la mejoría clínica en este grupo de pacientes. Estos resultados sugieren que la talamotomía podría influenciar el circuito neuronal relacionado con el BP.

Integration of neocortical embryonal grafts with the neocortex of host rats examined by Leao's spreading cortical depression.

Cortical spreading depression (SD) was used to assess the density and organization of neural elements in neocortical transplants and their connectivity with the host brain. Embryonal neocortex (E14) was transplanted into cavities in the frontoparietal cortex of 3-month-old rats. SD elicited in the cortex of anesthetized host rats (n = 12) 3 to 8 months after transplantation did not penetrate into the grafts. SD could be elicited in large transplants but did not propagate to the surrounding host neocortex. Spontaneous unit activity in the transplants was affected by SD elicited in the neocortex of the host rats anesthetized with urethane. Most units (n = 49) displayed excitatory-inhibitory (52%) or inhibitory (29%) reactions, whereas purely excitatory reactions were less frequent (8%). The results suggest that the packing density of neurons in the transplant can support SD but that the conditions at the graft-host boundary (glial scar, scarcity of neurons) stop SD propagation. High reactivity of the graft neurons to SD in the host neocortex indicates that afferentation from the host brain represents an important, predominantly excitatory contribution to the spontaneous activity of the transplant.

Differential effect of ketamine on the reference and working memory versions of the Morris water maze task.

The assumption that blockade of long-term potentiation by N-methyl-D-aspartate antagonists interferes with spatial memory was supported by experiments showing that 15 mg/kg ketamine impairs acquisition of navigation to a hidden platform but not to a visible platform. Higher doses were required to impair retrieval of overtrained place navigation. In a working memory version of the task, retrieval latencies were shorter than acquisition latencies with 4- to 15-min but not with 30- and 60-min delays. Latent learning was only effective with the 4-min delay. Ketamine prolonged the initial search of the hidden platform at 3 mg/kg and impaired latent learning but not active acquisition at 1.5-10 mg/kg. Comparison of behavioral and synaptic effects of ketamine suggests that long-term potentiation is a necessary condition, but not a sufficient condition, for acquisition of place navigation, because search strategy and latent place learning are impaired by ketamine doses not interfering with this synaptic phenomenon.

Unilateral striatal grafts induce behavioral and electrophysiological asymmetry in rats with bilateral kainate lesions of the caudate nucleus

Rats (n=11) with bilateral kainate lesions of the caudate nucleus and subsequen unilateral transplantation of embryonic striatal tissue into the damaged area prefered 4 months later to reach for food with the forepaw contralateral to the graft. No such asymmetry was observed in lesioned, nontransplanted (n=8) or unoperated (n=5) control rats. Good integration of the graft with the host brain was indicated by the fnding that cortical spreading depression did not enter the lesioned caudate nucleus but did penetrate into the lesioned caudate with the graft almos as regulary as in intact rats. Behavioral asymmetry produced by unilateral grafts in bilaterally lesioned animals reveals the effects of transplantation with more sensitivity than the graft-induced compensation of the asymmetries caused by unilateral lesions

Systemic ketamine blocks cortical spreading depression but does not delay the onset of terminal anoxic depolarization in rats.

Ketamine (KET)-induced blockade of cortical spreading depression (CSD) was examined in rats (n = 51) anesthetized with pentobarbital (50 mg/kg). CSD was elicited by intracortical injection of 1 microliter of 0.15 mol/l potassium acetate 10-40 min after i.p. injection of 6-50 mg/kg KET. KET was almost ineffective at 6 mg/kg but prevented CSD propagation at 12 mg/kg and at higher dosages. The blockade was maximal 20 min after injection. Terminal anoxic depolarization elicited by N2 breathing developed in control rats after a latency which was not significantly different from that in rats pretreated with 50 and 100 mg/kg KET. The failure of CSD blocking dosages of KET to delay the onset of terminal anoxic depolarization indicates that excitotoxic amino acids play different roles in the mechanism of the anoxia-elicited and CSD-related autoregenerative ionic shifts.