ABSTRACT
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 neural(AU)
Subject(s)
Parkinson Disease , Subthalamic NucleusABSTRACT
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.
Subject(s)
Aging/physiology , Alzheimer Disease/physiopathology , Brain/physiology , Disease Models, Animal , Nerve Growth Factors/physiology , Animals , Fetal Tissue Transplantation , Hippocampus/surgery , Male , Mice , Mice, Inbred BALB C , Neuronal Plasticity/physiology , Rats , Rats, Sprague-Dawley , Septum Pellucidum/embryology , Septum Pellucidum/transplantationABSTRACT
INTRODUCTION: Transplantation of foetal dopaminergic cells has been extensively used as restorative treatment for Parkinson's disease. OBJECTIVE: This study was carried out to determine the survival, modifications in rotatory activity induced by D-amphetamine and total content of dopamine in the striatal and nigra regions of hemiparkinsonian rats which had had foetal mesencephalic cells simultaneously transplanted to the striatum and pars reticularis of the substancia nigra. MATERIAL AND METHODS: The study was done using adult male Wistar rats weighing 200-250 gms. The following experimental groups were formed, depending on the site of transplant: St: transplant to striatum (n = 2); SNr: transplant to SNr (n = 20), ST + Snr; transplant to striatum and SNr simultaneously n = 20; and control (lesion with no transplant) n = 20. We studied the rotatory activity induced by D-amphetamine 1, 2, 3 and 6 months after transplantation. After this time the rats were deeply anaesthetized and randomly allocated for morphological study or biochemical determination of the total dopamine content in the St and SNr using the HPLC technique. RESULTS: Study of conduct showed no significant differences in rotatory activity induced by D-amphetamine between the groups with intrastriatal transplants, but there was a difference between these and the SNr and control groups. Biochemical analysis showed that striatal DA content was significantly greater in the ST for the groups with intrastriatal transplants. The content of substancia nigra DA was significantly greater in the SNr of the ST + SNr group, followed by the ST group. Morphometric study showed differences, which were not significant, between ST transplanted animals and significant differences between the SNr transplanted group with a significant increase in survival of the SNr of the ST + SNr group. CONCLUSIONS: These results suggest a positive effect due to intrastriatal transplants compared to survival following intranigral transplants.
Subject(s)
Adrenergic Agents/pharmacokinetics , Corpus Striatum/chemistry , Corpus Striatum/surgery , Dopamine/analysis , Dopamine/physiology , Fetal Tissue Transplantation/methods , Functional Laterality , Mesencephalon , Parkinson Disease/surgery , Substantia Nigra/chemistry , Substantia Nigra/surgery , Analysis of Variance , Animals , Cell Count , Chromatography, High Pressure Liquid/methods , Corpus Striatum/metabolism , Male , Mesencephalon/cytology , Mesencephalon/embryology , Mesencephalon/transplantation , Oxidopamine/pharmacokinetics , Rats , Rats, Wistar , Substantia Nigra/metabolism , Time FactorsABSTRACT
The possibilities of neural transplantation were studied in functional motor recovery of 21-23-month-old Sprague-Dawley male rats. Age-dependent functional losses of rats were evaluated using the Marshall scale for swimming abilities, narrow bridge task and suspension on horizontal wire. Fifteen rats exhibited motor disabilities when were compared with young control rats. Deficient rats were divided in two groups: one group received dissociated fetal dopaminergic cells from ventral mesencephalon (E12-E14) to striatum, whereas the other group having the same level of impairment, was followed without any graft and served as age-matched controls. Cell survival and behavior were evaluated twelve weeks after grafting by immunocytochemistry (tyrosine hydroxylase=TH) and the same behavioral test battery.
ABSTRACT
Aged, cognitively impaired rats were transplanted with septal fetal cells into hippocampus on both sides. Behavioral testing 12 weeks after grafting revealed a significant improvement of the transplanted animals in relation to the non-grafted, age-matched controls. Oxotremorine-induced theta activity was recorded in the transplanted animals, without any difference in regard to young, or age-matched controls, suggesting that the transplant had not affected the hippocampal structure. Acetylcholine esterase (AChE) histochemistry demonstrated the survival of cholinergic cells within the transplant. The grafted cells remained clustered near or in the hippocampal formation without disrupting its structure. The beneficial effects of the transplant are discussed in relation to its possible mechanisms, and applications to human therapy.
