Sulforaphane protects from myocardial ischemia-reperfusion damage through the balanced activation of Nrf2/AhR.

The activation of the transcription factor Nrf2 and the consequent increment in the antioxidant response might be a powerful strategy to contend against reperfusion damage. In this study we compared the effectiveness between sulforaphane (SFN), a well known activator of Nrf2 and the mechanical maneuver of post-conditioning (PostC) to confer cardioprotection in an in vivo cardiac ischemia-reperfusion model. We also evaluated if additional mechanisms, besides Nrf2 activation contribute to cardioprotection. Our results showed that SFN exerts an enhanced protective response as compared to PostC. Bot, strategies preserved cardiac function, decreased infarct size, oxidative stress and inflammation, through common protective pathways; however, the aryl hydrocarbon receptor (AhR) also participated in the protection conferred by SFN. Our data suggest that SFN-mediated cardioprotection involves transient Nrf2 activation, followed by phase I enzymes upregulation at the end of reperfusion, as a long-term protection mechanism.

Prolactin prevents mitochondrial dysfunction induced by glutamate excitotoxicity in hippocampal neurons.

Prolactin (PRL) is a pleiotropic hormone secreted by several cells and tissues in the body, such as mammary glands, T-lymphocytes, hypothalamus, among others. This hormone possess neuroprotective properties against glutamate-excitotoxicity through the activation of NF-kB, suggesting it could exert an antioxidant action. However, the role of PRL on the antioxidant defense during glutamate-induced excitotoxicity is not clear to date. Therefore, in the present study, we have evaluated the effect of PRL on SOD activity and protein content of both of its isoforms (Mn2+-SOD and Cu2+/Zn2+-SOD), as well as, its action on mitochondrial activity in primary culture of hippocampal neurons of rats. Additionally, we have evaluated the possible antioxidant effect of PRL through the determination of lipid peroxidation products (LPO), measured as malondialdehyde (MDA). Results show that PRL enhances the activity and the protein content of Mn2+-SOD and Cu2+/Zn2+-SOD in neurons exposed to glutamate-induced excitotoxicity. Moreover, our results demonstrate that PRL prevents mitochondrial dysfunction induced by glutamate and significantly decreases the levels of LPO products. To our knowledge, this is the first time that a potential antioxidant effect of PRL has been described in hippocampal neurons exposed to glutamate excitotoxicity, opening questions of its potentiality for therapeutics.

What can man do without basal ganglia motor output? The effect of combined unilateral subthalamotomy and pallidotomy in a patient with Parkinson's disease.

We have studied motor performance in a man with Parkinson's disease (PD) in whom thermolytic lesions of the left subthalamic and left globus pallidus nuclei interrupted the basal ganglia (BG)-thalamo-cortical motor circuit in the left hemisphere. This allowed us to study remaining motor capabilities in the absence of aberrant BG activity typical of PD. Movements of the left arm were slow and parkinsonian whereas movement speed and simple reaction times (RT) of the right (operated) arm were within the normal range with no obvious deficits in a range of daily life activities. Two main abnormalities were found with the right hand. (a) Implicit sequence learning in a probabilistic serial reaction time task was absent. (b) In a go/no-go task when the percent of no-go trials increased, the RT superiority with the right hand was lost. These deficits are best explained by a failure of the cortex, deprived of BG input, to facilitate responses in a probabilistic context. Our findings confirm the idea that it is better to stop BG activity than allowing faulty activity to disrupt the motor system but dispute earlier claims that interrupting BG output in PD goes without an apparent deficit. From a practical viewpoint, our observations indicate that the risk of persistent dyskinesias need not be viewed as a contraindication to subthalamotomy in PD patients since they can be eliminated if necessary by a subsequent pallidotomy without producing deficits that impair activities of daily life.

Monitoring system for isolated limb perfusion based on a portable gamma camera.

BACKGROUND: The treatment of malignant melanoma or sarcomas on a limb using extremity perfusion with tumour necrosis factor (TNF-alpha) and melphalan can result in a high degree of systemic toxicity if there is any leakage from the isolated blood territory of the limb into the systemic vascular territory. Leakage is currently controlled by using radiotracers and heavy external probes in a procedure that requires continuous manual calculations. The aim of this work was to develop a light, easily transportable system to monitor limb perfusion leakage by controlling systemic blood pool radioactivity with a portable gamma camera adapted for intraoperative use as an external probe, and to initiate its application in the treatment of MM patients. METHODS: A special collimator was built for maximal sensitivity. Software for acquisition and data processing in real time was developed. After testing the adequacy of the system, it was used to monitor limb perfusion leakage in 16 patients with malignant melanoma to be treated with perfusion of TNF-alpha and melphalan. RESULTS: The field of view of the detector system was 13.8 cm, which is appropriate for the monitoring, since the area to be controlled was the precordial zone. The sensitivity of the system was 257 cps/MBq. When the percentage of leakage reaches 10% the associated absolute error is +/-1%. After a mean follow-up period of 12 months, no patients have shown any significant or lasting side-effects. Partial or complete remission of lesions was seen in 9 out of 16 patients (56%) after HILP with TNF-alpha and melphalan. CONCLUSION: The detector system together with specially developed software provides a suitable automatic continuous monitoring system of any leakage that may occur during limb perfusion. This technique has been successfully implemented in patients for whom perfusion with TNF-alpha and melphalan has been indicated.

Therapeutic efficacy of unilateral subthalamotomy in Parkinson's disease: results in 89 patients followed for up to 36 months.

BACKGROUND: Stereotactic thermocoagulative lesions of the subthalamic nucleus (STN) have been shown to induce significant motor improvement in patients with Parkinson's disease (PD). PATIENTS AND METHODS: 89 patients with PD were treated with unilateral subthalamotomy. 68 patients were available for evaluations after 12 months, 36 at 24 months and 25 at 36 months. RESULTS: The Unified Parkinson's Disease Rating Scale (UPDRS) motor scores improved significantly contralaterally to the lesion in the "off" and "on" states throughout the follow-up, except for the "on" state at the last evaluation. Axial features and signs ipsilateral to the lesion progressed steadily throughout the study. Levodopa daily doses were significantly reduced by 45%, 36% and 28% at 12, 24 and 36 months post-surgery. 14 patients (15%) developed postoperative hemichorea-ballism which required pallidotomy in eight. These 14 patients had significantly higher dyskinesia scores (levodopa induced) preoperatively than the entire cohort. CONCLUSION: Unilateral subthalamotomy was associated with significant and sustained motor benefit contralateral to the lesion. Further work is needed to ascertain what factors led to severe, persistent chorea-ballism in a subset of patients. Subthalamotomy may be considered an option in circumstances when deep brain stimulation is not viable.

Performance tests of two portable mini gamma cameras for medical applications.

We have developed two prototypes of portable gamma cameras for medical applications based on a previous prototype designed and tested by our group. These cameras use a CsI(Na) continuous scintillation crystal coupled to the new flat-panel-type multianode position-sensitive photomultiplier tube, H8500 from Hamamatsu Photonics. One of the prototypes, mainly intended for intrasurgical use, has a field of view of 44 x 44 mm2, and weighs 1.2 kg. Its intrinsic resolution is better than 1.5 mm and its energy resolution is about 13% at 140 keV. The second prototype, mainly intended for osteological, renal, mammary, and endocrine (thyroid, parathyroid, and suprarenal) scintigraphies, weighs a total of 2 kg. Its average spatial resolution is 2 mm; it has a field of view of 95 x 95 mm2, with an energy resolution of about 15% at 140 keV. The main advantages of these gamma camera prototypes with respect to those previously reported in the literature are high portability and low weight, with no significant loss of sensitivity and spatial resolution. All the electronic components are packed inside the mini gamma cameras, and no external electronic devices are required. The cameras are only connected through the universal serial bus port to a portable PC. In this paper, we present the design of the cameras and describe the procedures that have led us to choose their configuration together with the most important performance features of the cameras. For one of the prototypes, clinical tests on melanoma patients are presented and images are compared with those obtained with a conventional camera.

[Optimization of use of levodopa in Parkinson's disease: role of levodopa-carbidopa-entacapone combination]. / Optimización del uso de la levodopa en la enfermedad de Parkinson: papel de la combinación levodopacarbidopa- entacapona.

Levodopa remains the mainstay treatment for Parkinson's disease (PD). Chronic treatment is associated with motor complications (MC) that marred the clinical benefit of levodopa. These problems and experimental data in cell cultures indicating a neurotoxic effect of levodopa have led to the idea of delaying the introduction of levodopa treatment for as long as possible. We here review recent data regarding the mechanism of action of levodopa and its application in clinical practice on the light of the marketing of the combination levodopa-carbidopa- entacapone. Accumulated evidence indicates that MC are mainly the consequence of disease severity governing the degree of dopaminergic depletion and the "pulsatile" dopaminergic stimulation provided by levodopa short plasma half-life. There is no in vivo or clinical evidence of a relevant neurotoxic effect of levodopa. In fact, the recent ELLDOPA study may suggest a neuroprotective effect. Entacapone reduces homocysteine plasma levels which could provide a mechanism to reduce cell death in PD. Currently, the combination levodopa-carbidopa-entacapone is particularly indicated for the treatment of "wearing off" fluctuations. Experimental evidence suggests that early treatment with levodopa-carbidopa-entacapone may substantially ameliorate the incidence of MC. Such a clinical study in "de novo" patients is underway. At present, the combination levodopa-carbidopa-entacapone is indicated when levodopa is judged necessary.

Optimización del uso de la levodopa en la enfermedad de Parkinson: papel de la combinación levodopa-carbidopa-entacapona / Optimization of use of levodopa in Parkinson's disease: role of levodopacarbidopa -entacapone combination

La levodopa continúa considerándose el fármaco más útil en el tratamiento de la enfermedad de Parkinson (EP), pero se asocia con la aparición de complicaciones motoras (CM). Estudios experimentales en la rata y el mono indican que el uso de levodopa asociada a benserazida o carbidopa ya entacapona (triple combinación) se asocia con menor incidencia de discinesias. Estudios en pacientes indican que la triple combinación proporciona un estímulo dopaminérgico más estable, acercándose en mayor medida a reponer la estimulación dopaminérgica continua que caracteriza fisiológicamente al sistema nigroestriatal. No existe evidencia de un efecto neurotóxico de la levodopa en la EP. La discrepancia entre los resultados in vitro e in vivo está principalmente relacionada con la ausencia de células de la glía en los cultivos celulares y bajos niveles de ácido ascórbico. La entacapona bloquea la elevación de homocisteína plasmática inducida por levodopa. lo cual podría ser un mecanismo protector de la muerte celular en la EP. La aplicación clínica de levodopa-carbidopa-entacapona está indicada en pacientes con «deterioro de fin de dosis)}. Los estudios experimentales sugieren que la utilización inicial de esta combinación puede reducir la incidencia de CM. Se está llevando a cabo un estudio clínico multicéntrico para analizar esta hipótesis. Provisionalmente se recomienda la asociación levodopa-carbidopa-entacapona cuando se decida añadir levodopa al tratamiento de la EP

Levodopa remains the mainstay treatment for Parkinson's disease (PD). Chronic treatment is associated with motor complications (MC) that marred the clinical benefit of levodopa. These problems and experimental data in cell cultures indicating a neurotoxic effect of levodopa have led to the idea of delaying the introduction of levodopa treatment for as long as possible. We here review recent data regarding the mechanism of action of levodopa and its application in clinical practice on the light of the marketing of the combination levodopa-carbidopa-entacapone. Accumulated evidence indicates that MC are mainly the consequence of disease severity governing the degree of dopaminergic depletion and the “pulsatile” dopaminergic stimulation provided by levodopa short plasma half-life. There is no in vivo or clinical evidence of a relevant neurotoxic effect of levodopa. In fact, the recent ELLDOPA study may suggest a neuroprotective effect. Entacapone reduces homocysteine plasma levels which could provide a mechanism to reduce cell death in PD. Currently, the combination levodopa-carbidopa-entacapone is particularly indicated for the treatment of «wearing off» fluctuations. Experimental evidence suggests that early treatment with levodopa-carbidopa-entacapone may substantially ameliorate the incidence of Me. Such a clinical study in ((de novo)} patients is underway. At present, the combination levodopa-carbidopaentacapone is indicated when levodopa is judged necessary

Bilateral subthalamotomy in Parkinson's disease: initial and long-term response

We conducted an open label pilot study of the effect of bilateral subthalamotomy in 18 patients with advanced Parkinson's disease. In seven patients, the first subthalamotomy pre-dated the second by 12-24 months (staged surgery). Subsequently, a second group of 11 patients received bilateral subthalamotomy on the same day (simultaneous surgery). Patients were assessed according to the CAPIT (Core Assessment Program for Intracerebral Transplantation) protocol, a battery of timed motor tests and neuropsychological tests. Evaluations were performed in the off and on drug states before surgery and at 1 and 6 months and every year thereafter for a minimum of 3 years after bilateral subthalamotomy. Compared with baseline, bilateral subthalamotomy induced a significant (P < 0.001) reduction in the 'off' (49.5 percent) and on (35.5 percent) Unified Parkinson's Disease Rating Scale (UPDRS) motor scores at the last assessment. A blind rating of videotape motor exams in the off and on medication states preoperatively and at 2 years postoperatively also revealed a significant improvement...(AU)

Bilateral subthalamotomy in Parkinson's disease: initial and long-term response.

We conducted an open label pilot study of the effect of bilateral subthalamotomy in 18 patients with advanced Parkinson's disease. In seven patients, the first subthalamotomy pre-dated the second by 12-24 months ('staged surgery'). Subsequently, a second group of 11 patients received bilateral subthalamotomy on the same day ('simultaneous surgery'). Patients were assessed according to the CAPIT (Core Assessment Program for Intracerebral Transplantation) protocol, a battery of timed motor tests and neuropsychological tests. Evaluations were performed in the 'off' and 'on' drug states before surgery and at 1 and 6 months and every year thereafter for a minimum of 3 years after bilateral subthalamotomy. Compared with baseline, bilateral subthalamotomy induced a significant (P < 0.001) reduction in the 'off' (49.5%) and 'on' (35.5%) Unified Parkinson's Disease Rating Scale (UPDRS) motor scores at the last assessment. A blind rating of videotape motor exams in the 'off' and 'on' medication states preoperatively and at 2 years postoperatively also revealed a significant improvement. All of the cardinal features of Parkinson's disease as well as activities of daily living (ADL) scores significantly improved (P < 0.01). Levodopa-induced dyskinesias were reduced by 50% (P < 0.01), and the mean daily levodopa dose was reduced by 47% at the time of the last evaluation compared with baseline (P < 0.0001). Dyskinesias occurred intraoperatively or in the immediate postoperative hours in 13 patients, but were generally mild and short lasting. Three patients developed severe generalized chorea that gradually resolved within the next 3-6 months. Three patients experienced severe and persistent postoperative dysarthria. In two, this coincided with the patients exhibiting large bilateral lesions also suffering from severe dyskinesias. No patient exhibited permanent cognitive impairment. The motor benefit has persisted for a follow-up of 3-6 years. This study indicates that bilateral subthalamotomy may induce a significant and long-lasting improvement of advanced Parkinson's disease, but the clinical outcome was variable. This variability may depend in large part on the precise location and volume of the lesions. Further refinement of the surgical procedure is mandatory.

Design and tests of a portable mini gamma camera.

Design optimization, manufacturing, and tests, both laboratory and clinical, of a portable gamma camera for medical applications are presented. This camera, based on a continuous scintillation crystal and a position-sensitive photomultiplier tube, has an intrinsic spatial resolution of approximately 2 mm, an energy resolution of 13% at 140 keV, and linearities of 0.28 mm (absolute) and 0.15 mm (differential), with a useful field of view of 4.6 cm diameter. Our camera can image small organs with high efficiency and so it can address the demand for devices of specific clinical applications like thyroid and sentinel node scintigraphy as well as scintimammography and radio-guided surgery. The main advantages of the gamma camera with respect to those previously reported in the literature are high portability, low cost, and weight (2 kg), with no significant loss of sensitivity and spatial resolution. All the electronic components are packed inside the minigamma camera, and no external electronic devices are required. The camera is only connected through the universal serial bus port to a portable personal computer (PC), where a specific software allows to control both the camera parameters and the measuring process, by displaying on the PC the acquired image on "real time." In this article, we present the camera and describe the procedures that have led us to choose its configuration. Laboratory and clinical tests are presented together with diagnostic capabilities of the gamma camera.

[Changes in nerve growth factor levels related to age and neurotrophic treatment in non-human primate]. / Cambios en los niveles de factor de crecimiento nervioso con el envejecimiento y el tratamiento neurotrófico en primates no humanos.

INTRODUCTION: To examine the amounts and role of growth factors in different tissues and corporal fluid, new sensitive techniques have to be developed. A major problem is that the normal concentration of trophic substances, such as nerve growth factor (NGF), in central and peripheral nervous system and in fluids is very low (ng pg/ml). A valuable method of research is the sensitive two site enzyme immunoassay using the monoclonal antibody 27/21 to mouse NGF. Materials and methods. The present work applied this enzyme immunoassay to examine the NGF levels in normal non human primate sera (n= 94) and applied this assay to study of NGF levels in two non human primate receiving NGF infusion: one young and one aged. Two groups of non human primate sera were studied one young adult (n= 69) and one aged (n= 25). The serum samples NGF treated non human primate were taken before the infusion and at the 1st week and 1st, 3rd, 6th and 12th month after infusion. RESULTS: To further test the specificity of conjugate binding, dilutions of the non human primate sera were preincubated with an excess of monoclonal NGF antibody 27/21 in solution. With this strategy it was possible to completely block the signal obtained using the enzyme immunoassay. We found very low levels of NGF in aged monkeys (0.054 ng/ml) when compared with young adult group (0.152 ng/ml) (p> 0.01). The NGF levels in aged non human primate treatment with NGF was very low before (0.50 ng/ml) and during NGF treatment evolution time, whereas at the the 12th month showed an increase in NGF levels (0.180 ng/ml). We found normal values of NGF in the young monkey before and during the first year after NGF infusion. CONCLUSIONS: Using the enzyme immunoassay described it is possible to know the serum concentration of NGF immunoreactive in non human primate and this assay is able to detect peripheral changes in NGF levels after intracerebral infusion of NGF.

Cambios en los niveles de factor de crecimiento nervioso con el envejecimiento y el tratamiento neurotrófico en primates no humanos / Change in nerve growth factor levels related to age and neurotrophic treated in non-human primate

Introducción. Las concentraciones normales de factor de crecimiento nervioso (NGF, del inglés Nerve Growth Factor) en tejido y fluidos corporales son bajas (ng-pg/ml). Un método muy utilizado para cuantificar NGF es el ensayo inmunoenzimático de doble sitio con el anticuerpo 27/21 anti-NGF murino (NGFm). Material y métodos. El presente trabajo valida la utilidad de un ensayo inmunoenzimático para examinar los niveles séricos de NGF en primates no humanos normales de diferentes géneros y especies; y aplica este ensayo al estudio evolutivo de NGF en el suero de dos primates no humanos, uno joven y otro viejo, con infusión intracerebroventricular de NGFm.Para validar la detección inmunológica de NGF en suero de primates no humanos se añadió al ensayo inmunoenzimático un paso de bloqueo con anti-NGFm. Los primates no humanos normales se agruparon según los siguientes parámetros: edad (joven-adulto, n= 69, y viejo, n= 25), sexo (masculino, n= 74, y femenino, n= 20) y género o especie. Las muestras de suero de los primates no humanos con tratamiento trófico se tomaron antes y después de la infusión (semana: 1, mes: 3, 6 y 12). Resultados. Mediante la adición de un paso de bloqueo con anti-NGFm se demostró la detección inmunológica de NGF en suero de primates no humanos. Los valores de NGF encontrados en el grupo de primates no humanos jóvenes-adultos (0,152 ng/ml) son superiores a los detectados en primates no humanos viejos (0,054 ng/ml) (p< 0,01). Los niveles de NGF en el mono viejo tratado con NGF, antes (0,050 pg/ml) y durante los primeros meses posteriores al tratamiento, fueron bajos o indetectables, al año de evolución, se detectó un aumento de NGF (0,180 ng/ml) . El mono joven antes de la infusión mostró niveles similares a los del grupo control pareado en edad (0,261 ng/ ml), mientras que a los dos meses posteriores al tratamiento trófico se observó un incremento (0,380 ng/ml) de NGF a nivel periférico. Conclusión. El ensayo inmunoenzimático descrito es capaz de cuantificar NGF inmunorreactivo en suero de primates no humanos y de detectar cambios periféricos en los niveles de NGF después del tratamiento intracerebroventricular con NGF (AU)

Dorsal subthalamotomy for Parkinson's disease.

We report our experience of unilateral subthalamotomy in patients with Parkinson's disease (PD). Eleven patients were included in a pilot, open-labeled study to assess the effect of unilateral lesion of the subthalamic nucleus (STN) with a minimum of 12 months of follow-up. The guidelines of CAPIT (Core Assessment Program for Intracerebral Transplantation) were followed for recruitment into the study and follow-up assessment. Levodopa equivalents daily intake (mean 967 mg) were unchanged during the first 12 months in all but one patient who stopped medication. The sensorimotor region of the STN was defined by semimicrorecording and stimulation and a thermolytic lesion was placed accordingly. There was a significant reduction in both UPDRS parts II and III in the "off" state at 1-, 6-, and 12-month follow-up. This effect was maintained in four patients up to 24 months. The dyskinesia score did not change postoperatively. Lesion-induced dyskinesias were not a management problem except in one patient who developed a large infarction several days postsurgery. This initial study indicates that a lesion of the STN is not generally associated with hemiballismus in PD. Subthalamotomy may induce considerable motor benefit and could become another surgical option under specific circumstances.

[Simultaneous micro-transplantation of fetal mesencephalic cells to the striate and substantia nigra pars reticulata in hemi-parkinsonian rats. A study of behavior]. / Microtrasplante simultáneo de células mesencefálicas fetales en estriado y substantia nigra pars reticulata de ratas hemiparkinsonianas. Estudio conductual.

INTRODUCTION: Microtransplantation of fetal dopaminergic cells has been used over the past ten years with good results in models of Parkinson's disease. OBJECTIVE: To evaluate the effect of microtransplantation of fetal dopaminergic cells 'seeded' in the substantia nigra pars reticulata (SNpr) and striate (St) simultaneously. MATERIAL AND METHODS: The animals received a transplant or microtransplant of cells into the St and SNpr ipsilateral to the lesion in the substantia nigra pars compacta or to both regions. Depending on the site and technique used the following experimental groups were considered: I. Macrotransplantation to the St (n = 20); II. Microtransplant to the St (n = 20); III. Microtransplant to St + SNpr (n = 20); IV. Microtransplant to St + SNpr (n = 20); V. Macrotransplantation to SNpr (n = 20); VI. Microtransplantation to SNpr (n = 20); and VII. Control (lesion only) (n = 20). The rotations induced by D-amphetamine (5 mg/kg i.p.) and by apomorphine were studied 1, 2, 3 and 6 months and 3 and 6 months respectively after transplantation. Three months after transplantation we studied the motor asymmetry shown by the animals by means of the ladder test. RESULTS: The rotations were reduced in the groups with intrastriate transplantation. Comparison between the surgical techniques showed nonsignificant differences between them. The ladder test showed significant differences in use of the limbs in all experimental groups. Use of the left limb was significantly reduced in all groups. CONCLUSIONS: Modification of the rotations seems more sensitive to the site of transplant than to the technique used. It seems that the skills studied using the ladder test are not altered by the microtransplant technique.

Microtrasplante simultáneo de células mesencefálicas fetales en estriado y substantia nigra pars reticulata de ratas hemiparkinsonianas. Estudio conductual / Simultaneous microtransplantation of fetal mesencephalic cells to the striate and substantia nigra pars reticulata in hemiparkinsonian rats. A study of conduct

Introducción. El microtrasplante de células dopaminérgicas fetales se ha utilizado en la última década con resultados relevantes en modelos de enfermedad de Parkinson. Objetivo. Evaluar el efecto del microtrasplante de células dopaminérgicas fetales `sembradas' en la substantia nigra pars reticulata (SNpr) simultáneamente con el estriado (Est). Material y métodos. Los animales recibieron trasplante o microtrasplante de células en el estriado y la SNpr ipsilateral a la lesión de la substantia nigra pars compacta o en ambos. De acuerdo con el sitio y la técnica utilizada se consideraron los siguientes grupos experimentales: I. Macrotrasplante en Est (n= 20); II. Microtrasplante en Est (n= 20); III. Macrotrasplante en Est + SNpr (n= 20); IV. Microtrasplante en Est + SNpr (n= 20); V. Macrotrasplante en SNpr (n= 20); VI. Microtrasplante en SNpr (n= 20), y VII. Control (sólo lesión) (n= 20). Las rotaciones inducidas por D-anfetamina (5 mg/kg ip) y por apomorfina fueron estudiadas 1, 2, 3 y 6 meses, y 3 y 6 meses, respectivamente, después del trasplante. Tres meses después del trasplante se estudió la asimetría motora que presentaban los animales a través de la prueba de la escalera. Resultados. Las rotaciones disminuyeron en los grupos con trasplante intraestriatal. La comparación de las técnicas quirúrgicas mostró diferencias no significativas entre ellas. La prueba de la escalera reveló diferencias significativas en la utilización de las extremidades en todos los grupos experimentales. La utilización de la extremidad izquierda disminuyó significativamente en todos los grupos.Conclusiones. La modificación de las rotaciones parece ser más sensible al sitio de trasplante que a la técnica utilizada en cuestión. Las habilidades que se estudian con la prueba de la escalera no parecen ser susceptibles de modificarse con la técnica de microtrasplante (AU)

[Simultaneous transplantation of fetal mesencephalic cells to the striatum and globus pallidus of rats with lesions induced by 6-hydroxydopamine]. / Trasplante simultáneo de células mesencefálicas fetales en striatum y globus pallidus de ratas con lesión por 6-hidroxidopamina.

INTRODUCTION: Studies of neural transplants in experimental models of Parkinson's disease have concentrated their attention on ectopic transplants of foetal mesencephalic cells to denervated striatum. However, the external globus pallidus has recently been shown to play an important part in the physiopathology of this disease. OBJECTIVE: Bearing in mind the importance of loss of extra-striatal dopamine in the genesis of the clinical signs found in parkinsonism, the objective of this study was to evaluate the effect of foetal mesencephalic transplantation to the globus pallidus of hemiparkinsonian rats. MATERIAL AND METHODS: Following conventional transplantation methodolgy, suspensions of cells from the ventral mesencephalum of rat embryos (E-14) were implanted. The tissue was grafted into the striatum, pallidum-striatum and pallidum areas of rats with unilateral lesions of the striatonigral bundle. One, two, three and six months after transplantation, the rotatory activity induced by D-amphetamine was evaluated. The rotatory behaviour induced by apomorphine was evaluated at three months. Motor ability of the front legs was evaluated in all experimental groups three months after transplantation using the 'ladder test'. RESULTS: In the experimental groups in which a transplant was made to the globus pallidus there was a significant reduction (p < 0.01) in rotatory activity induced by D-amphetamine and by apomorphine as compared with the non-transplanted groups. CONCLUSIONS: Transplants of foetal dopaminergic cells survive in the globus pallidus of hemiparkinsonian rats and can improve the rotational activity induced by dopaminergic agonists.

[Factors that lead to death of neurons in neurodegenerative diseases]. / Factores que desencadenan la muerte neuronal en enfermedades neurodegenerativas.

OBJECTIVE: The objective of this paper was to review information related to the various factors which may trigger the mechanisms of cell death, induced or programmed, which take place in the nervous system and their relationship with the aetiopathogenesis of the neurodegenerative diseases. DEVELOPMENT: In recent years it has been recognized that cell death may be not only the consequence of accidental damage but also a sign of a suicide programme. This form of death is currently known as apoptosis. It is a process which is morphologically distinct from accidental cell death or necrosis. It does not cause an inflammatory response. This type of death is not only involved in the development and haemostasis of tissues, but also in setting off neuronal degeneration in experimental models of Parkinson's disease, Huntington's chorea, etc. CONCLUSIONS: In the cell death occurring in neurodegenerative diseases there is more than one induction mechanisms. Understanding the factors which trigger cell death, and the chain of events leading to this, gives grounds for the design of new pharmacological strategies for the treatment of these diseases.

[Behavioral evaluation of the unilateral lesion model in rats using 6-hydroxydopamine. Correlation between the rotations induced by D-amphetamine, apomorphine and the manual dexterity test]. / Evaluación conductual del modelo de lesión unilateral en ratas con 6-hidroxidopamina. Correlación entre las rotaciones inducidas por D-anfetamina, apomorfina y la prueba de habilidades manuales.

INTRODUCTION: Evaluation of rotatory activity induced by dopaminergic agonists is the most widely used test of conduct for the measurement of dopaminergic depletion of a unilateral lesion of the striatonigral pathway caused by 6-hydroxydopamine (6-OHDA) in rats, since it is quantitatively related to the extension of the dopaminergic denervation. OBJECTIVE: The objective of this study was to evaluate, from different angles, the changes in conduct seen in the model of unilateral lesion with 6-OHDA and to establish correlation with the rotation induced by D-amphetamine and by apomorphine and the ladder test. MATERIAL AND METHODS: Male Wistar rats were used. Lesions were produced in the SNpc by stereotactic injection of 6-OHDA into the right hemisphere and the effectiveness of the lesions was studied using the rotary conduct induced by D-amphetamine and apomorphine. The motor ability of the front legs was measured by the ladder test, carried out under standard and forced conditions. RESULTS: All the animals with lesions had difficulty in reaching food with both legs, although the most pronounced deficit was in the leg contralateral to the lesion. The ladder test correlated better with rotatory activity induced by apomorphine than by D-amphetamine. CONCLUSION: The animals with most dopamine loss showed most deficient use of their front legs.

[Obtention and characterization of murine beta-NGF. Application in a model of cerebral aging]. / Obtención y caracterización del beta-NGF murino. Aplicación en un modelo de envejecimiento cerebral.

INTRODUCTION: beta-NGF is a basic protein of 118 aminoacids which acts are a trophic factor for sensory and sympathetic neurons of the peripheral nervous system, and on cholinergic neurons of the anterior basal cerebrum. OBJECTIVES: In view of the functional effect of beta-HGF and its possibilities as a therapeutic agent in neurodegenerative disease, including Alzheimer's disease in this study our aim was to obtain, characterize and show the main results of the application of beta-NGFm in a model of cerebral ageing in rats with cognitive disorders. MATERIAL AND METHODS: For the obtention of beta-NGFm we followed Mobley's method as modified by Ebendal and used mouse submaxillary gland as a source of raw material. The characterization studies were carried out by application of seven techniques which allowed physicochemical characterization and demonstration of the biological activity of the product. Application of beta-NGF obtained under these conditions was carried out in a mode of cerebral ageing and the effects of treatment were assessed by conduct studies, measurement of the activity of the enzyme acetyl cholinesterase and study of neural plasticity. CONCLUSIONS: Characterization studies carried out on the beta-NGFm showed that the protein obtained consists of a mixture of molecules of beta-NGFm which are intact at their extreme N-Terminal, and molecules which have lost the octapeptide of the N-terminal position and show some modification increasing hydrophobicity. All these species were recognized immunologically by the specific antibody anti-NGFm and showed biological activity.