Atorvastatin protects GABAergic and dopaminergic neurons in the nigrostriatal system in an experimental rat model of transient focal cerebral ischemia / La atorvastatina protege las neuronas gabérgicas y dopaminérgicas del sistema nigroestriatal en un modelo experimental de isquemia cerebral focal transitoria en ratas

Introduction: Cerebral ischemia is the third leading cause of death and the primary cause of permanent disability worldwide. Atorvastatin is a promising drug with neuroprotective effects that may be useful for the treatment of stroke. However, the effects of atorvastatin on specific neuronal populations within the nigrostriatal system following cerebral ischemia are unknown. Objective: To evaluate the effects of atorvastatin on dopaminergic and GABAergic neuronal populations in exofocal brain regions in a model of transient occlusion of the middle cerebral artery. Materials and methods: Twenty-eight male eight-week-old Wistar rats were used in this study. Both sham and ischemic rats were treated with atorvastatin (10 mg/kg) or carboxymethylcellulose (placebo) by gavage at 6, 24, 48 and 72 hours post-reperfusion. We analyzed the immunoreactivity of glutamic acid decarboxylase and tyrosine hydroxylase in the globus pallidus, caudate putamen and substantia nigra. Results: We observed neurological damage and cell loss in the caudate putamen following ischemia. We also found an increase in tyrosine hydroxylase immunoreactivity in the medial globus pallidus and substantia nigra reticulata, as well as a decrease in glutamic acid decarboxylase immunoreactivity in the lateral globus pallidus in ischemic animals treated with a placebo. However, atorvastatin treatment was able to reverse these effects, significantly decreasing tyrosine hydroxylase levels in the medial globus pallidus and substantia nigra reticulata and significantly increasing glutamic acid decarboxylase levels in the lateral globus pallidus. Conclusion: Our data suggest that post-ischemia treatment with atorvastatin can have neuro-protective effects in exofocal regions far from the ischemic core by modulating the GABAergic and dopaminergic neuronal populations in the nigrostriatal system, which could be useful for preventing neurological disorders.

Introducción. La isquemia cerebral es la tercera causa de muerte y la primera de discapacidad permanente en el mundo. La atorvastatina es un fármaco neuroprotector prometedor para el tratamiento de la apoplejía; sin embargo, su acción sobre las poblaciones neuronales del sistema nigroestriatal después de la isquemia aún se desconoce. Objetivo. Evaluar el efecto de la atorvastatina sobre poblaciones gabérgicas y dopaminérgicas en regiones exofocales en un modelo de oclusión transitoria de la arteria cerebral media. Materiales y métodos. Se utilizaron 28 ratas Wistar macho de ocho semanas de edad. Los ejemplares con isquemia simulada y los ejemplares sometidos a isquemia fueron tratados con atorvastatina (10 mg/kg) y carboximetilcelulosa (placebo) administrados por medio de sonda a las 6, 24, 48 y 72 horas después de la reperfusión. Se analizó la inmunorreacción de la descarboxilasa del ácido glutámico y de la tirosina hidroxilasa en el globo pálido, el putamen caudado y la sustancia negra. Resultados. Los datos confirmaron el daño neurológico y la pérdida celular en el putamen caudado. Se incrementó la inmunorreacción de la tirosina hidroxilasa en el globo pálido medial y la sustancia negra pars reticulata , disminuyendo la inmunorreacción de la descarboxilasa del ácido glutámico en el globo pálido lateral de los animales isquémicos tratados con placebo; sin embargo, el tratamiento con atorvastatina pudo revertirla, lo que logró una disminución significativa de la tirosina hidroxilasa en el globo pálido medial y la sustancia negra pars reticulata y aumentando los niveles de descarboxilasa del ácido glutámico en el globo pálido lateral. Conclusión. Nuestros datos sugieren que la atorvastatina en el tratamiento posterior a la isquemia ejerce neuroprotección en las zonas exofocales, modulando las poblaciones neuronales gabérgicas y dopaminérgicas del sistema nigroestriatal, lo que podría prevenir trastornos neurológicos.

Histological study on the effect of sodium azide on the corpus striatum of albino rats and the possible protective role of L-carnitine

Sodium azide is a white crystalline powder used as a broad-spectrum biocide in agriculture and as a preservative in aqueous laboratory reagents. The aim of this study was to determine the effect of sodium azide on the corpus striatum and the possible protection by L-carnitine. Twenty-four adult male albino rats, weighing 150-200 g, were used in this study. The animals were divided equally into four groups. Group I was the control group. Group II received sodium azide at a dose of 20 mg/kg/day orally for 60 consecutive days. Group III received sodium azide at the same previous dose in addition to L-carnitine at a dose of 100 mg/kg/day intraperitoneally for 60 consecutive days. Group IV received only L-carnitine at the same previous dose once daily for 60 consecutive days. At the end of the experiment, all the animals were anesthetized, the brain was dissected out and the regions of the corpus striatum were subjected to light and electron microscopic examination. Moreover, the number of degenerated nerve cells was counted and the results were analyzed statistically. By light and electron microscope, the nerve cells [pyramidal cells and granular cells] of group II animals showed degenerative changes in the form of shrunken darkly stained and hyperchromatic nuclei. Some apoptotic cells were observed. There were multinucleated giant cells in some areas and small vacuoles in the neuropil. Also, cytoplasmic vacuolations and swollen mitochondria with indistinct cristea were detected. The neuropil in some areas contained extravasation of blood elements. The nerve fibers showed fragmentation, thickening, aggregation, and defective myelination. Statistically, there was a highly significant increase in the mean number of degenerated neurons. In group III, L-carnitine preserved most of the histological and ultrastructural profile of the corpus striatum [nerve cells and nerve fibers], with a significant decrease in the rate of neuronal loss. The results of the current study showed that the administration of L-carnitine might protect against neurotoxicity produced by exposure to sodium azide

The microglia activation characteristics of MA-induced neurotoxicity in the rats striatum / 法医学杂志

OBJECTIVE@#To investigate the activation characteristics of microglia (MG) in the rats striatum with MA-induced neurotoxicity.@*METHODS@#Male Wistar rats were divided randomly into control group (n=24) and experimental group (n=24). The rats of experimental group were injected intraperitoneally with MA (15 mg/kg x 8 injections, at 12 hours interval). The rats of control group were administrated with saline. The tissues of striatum of two rat groups were harvested at 0.5 d, 1 d, 2 d, 3 d, 4 d, 5 d, 6 d and 7 d post initial administrations of MA or saline. The structure changes were observed by transmission electron microscopy and CD-11b immunohistochemistry. The ratio of activated MG was calculated and statistically analyzed.@*RESULTS@#In the control group, the morphological characteristics of the MG showed that the cell bodies were small with slender processes, high electronic density nucleus, and fewer organelles known as the "fork-type". In contrast, the MG in the MA-induced neurotoxicity group displayed larger cell body, shorter cell processes or disappeared, lower electronic density nucleus and rich organelles, resembling "bush-like" or "amoeba-like". The ratio of activated MG in control group was below 0.15 at all timepoints, whereas in the experimental group, the ratio of activated MG increased significantly from day 1 to day 7 (P<0.001).@*CONCLUSION@#The continuous MA stimulation of the CNS results in prominent MG activation.

Effect of sildenafil on the blood vessels [angiogenic effect] of adult rat striatal neurons

Sildenafil [Viagra] is a selective inhibitor of the cyclic guanosine monophosphate [cGMP] specific phosphodiesterase 5 [PDE5] used for the oral treatment of male erectile dysfunction of organic, psychogenic or mixed aetionlogy. The corpus striatum is the largest component of the basal ganglia which is located within the depth of each cerebral hemisphere and have a diverse function ranging from movement control, cognitive function and regulation of emotional behaviour. The study aimed to study the effect of sildenafil citrate on the striatal neurons of adult albino rats. Fifteen adult male albino rats would included in the study, ten of them were given 2mg/kg sildenafil citrate orally on alternate days for one month and five rats would taken as a controls. The animals were anaesthetized with ether and perfused with fixative solution, then the animals were decapitated and the brains were extracted. Slices of striatal neurons were carefully dissected and fixed in 5% buffered glutardehyde and electron microscopic technique was made and semithin and ultrathin sections were obtained and examined by light and electron microscopically. The results revealed severe dilatation and congestion of the blood vessels of rat striatal neurons compared to controls. This may be mediated through enhancement of nitric oxide [NO]-mediated effects. Sildenfil citrate induced angiogenic effect of adult male striatal neurons which may suggest that sildenfil may have a role in treatment of some neurological disorders such as multiple sclerosis and cerebrovascular stroke which may need further investigation

Bilateral basal ganglia lucencies following acute febrile illness.

Bilateral striatal necrosis in children without damage elsewhere in the brain can present as an acute neurological disorder or as a progressive disorder. Three children of 6, 7 and 12 years age developed dystonic posture of limbs without any cranial nerve involvement or alteration of sensorium soon after recovery from acute high grade febrile illness of 3-4 days duration. Computerized tomographic scan of head showed bilateral necrosis of basal ganglia. We think that these patients probably constitute a clinically and radiologically distinct subgroup of disorder that produce bilateral striatal necrosis in children. The cause of the syndrome is unknown.

Evaluación del efecto neuroprotector de lidocaína y ketamina en un modelo de hipoxia-isquemia cerebral en la rata: estudio histopatológico en estriado, hipocampo y corteza cerebral / Evaluation of the neuroprotective effect of lidocaine and ketamine on a cerebral hypoxia-ischemia model in the rat: histopathological analysis of the striatum, hippocampus and cerebral cortex

Los fectos de la lidocaína como droga protectora del Sistema Nervioso central por isquemia y traume han sido extensamente investigados sin conclusiones definitivas. Algunos experimentos que mostraban un efecto neuroprotector promisorio de la lidocaína utilizan como agente anestésico la ketamina sin considerar su posible contribución neuroprotectora en los resultados comunicados. Esto también se observa en otros experimentos que evalúan los efectos de varias drogas: bloqueadores orgánicos de los canales de calcio, recolectores de radicales libres, esteroides y ganglioosidos. La ketamina anestésico disociativo, es un análogo de feniciclidina, que actúa como un análogo de fenciclidina, que actúa como un antagonista no competitivo en le sitio del N-metil-D-aspartato, receptor subtipo glutamato, dela fenciclidina, y su acción neuroprotectora ha sido comunicada en varios modelos experimentales. El presente trabajo evalúa los efectos de la lidocaína y ketamina en el modelo de hipoxia-isquemia incompleta cerebral de la rata neonata (modelo Levine). Los resultados muestran un efcto neuroprotector significativo de la lidocaína y ketamina, evaluados por análisis hitopatológico del estriado, hipocampo y corteza cerebral-estriado en el modelo de la hipoxia-isquemia en modelo roedor vivo

Afasias subcorticales / Subcortical aphasias

Se presentan 25 pacientes con lesiones subcorticales izquierdas, comprobadas con tomografía computada cerebral. En 9 de ellos se encontró una afasia subcortical, generalmente sensorial transcortical: 3 pacientes tenían afasia global, 2 afasia de Wernicke, 1 caso tenía afasia amnésica, otra de Broca y otro afasia latente. Ocho pacientes no tuvieron afasia, pero 5 de ellos tenían una agrafía linguística. En 16 casos se encontró disartría y en 10 hipofonía. El análisis de esta experiencia y de la literatura permite concluir que las estructuras subcorticales forman parte del sistema funcional del lenguaje del habla y de la escritura