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1.
Arq. bras. neurocir ; 39(4): 284-288, 15/12/2020.
Artigo em Inglês | LILACS | ID: biblio-1362329

RESUMO

Discovered in 1865 by Jules Bernard Luys, the subthalamic nucleus is a set of small nuclei located in the diencephalon, inferior to the thalamus and superior to the substantia nigra, that can be visualized in a posterior coronal section. Histologically, it consists of neurons compactly distributed and filled with a large number of blood vessels and sparse myelinated fibers. This review presents an analysis of this anatomical region, considering what is most recent in the literature. Subthalamic neurons are excitatory and use glutamate as the neurotransmitter. In healthy individuals, these neurons are inhibited by nerve cells located in the side globus pallidus. However, if the fibers that make up the afferent circuit are damaged, the neurons become highly excitable, thus causing motor disturbances that can be classified as hyperkinetic, for example ballism and chorea, or hypokinetic, for example Parkinson disease (PD). The advent of deep brain stimulation has given the subthalamic nucleus great visibility. Studies reveal that the stimulation of this nucleus improves themotor symptoms of PD.


Assuntos
Núcleo Subtalâmico/anatomia & histologia , Núcleo Subtalâmico/anormalidades , Núcleo Subtalâmico/cirurgia , Doença de Parkinson , Substância Negra/anatomia & histologia , Córtex Cerebral/anatomia & histologia , Corpo Estriado/anatomia & histologia , Estimulação Encefálica Profunda/métodos , Globo Pálido/anatomia & histologia , Córtex Motor/anatomia & histologia
2.
Braz. j. med. biol. res ; 52(7): e8303, 2019. graf
Artigo em Inglês | LILACS | ID: biblio-1011594

RESUMO

Reinforcement omission effects (ROEs) are characterized by higher response rates after reinforcement omission than after reinforcement delivery. This pattern of behavior is interpreted in terms of motivational and attentional processes. Recent studies from our laboratory have shown that the amygdala, nucleus accumbens, and medial prefrontal cortex are involved in ROE modulation. Also, the literature has demonstrated a role of other areas such as substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA) in processes related to surprising events, such as prediction error and presentation or omission of an event (exteroceptive stimulus and reinforcement). Since these structures send projections to areas related to ROE modulation such as the amygdala, nucleus accumbens, and prefrontal cortex, the objective of the present study was to determine whether the SNc and VTA also integrate the circuit involved in ROE modulation. Rats were trained on a fixed-interval 12 s with limited-hold 6 s signaled schedule of reinforcement (Pre-lesion training). After acquisition of stable performance, the rats received bilateral neurotoxic lesions of the SNc (Experiment 1) and VTA (Experiment 2). Following postoperative recovery, the rats were submitted to two refresher sessions (Post-lesion training). Subsequently, the training was changed from a 100 to a 50% schedule of reinforcement (Post-lesion testing). In both experiments, the results showed that there was no difference in performance between sham rats and rats with bilateral lesions of the SNc or the VTA.


Assuntos
Animais , Masculino , Ratos , Reforço Psicológico , Comportamento Animal/fisiologia , Substância Negra/lesões , Área Tegmentar Ventral/lesões , Condicionamento Operante/fisiologia , Parte Compacta da Substância Negra/lesões , Substância Negra/fisiopatologia , Ratos Wistar , Área Tegmentar Ventral/fisiopatologia , Parte Compacta da Substância Negra/fisiopatologia , Aprendizagem/fisiologia
3.
Arq. neuropsiquiatr ; 74(9): 737-744, Sept. 2016. graf
Artigo em Inglês | LILACS | ID: lil-796045

RESUMO

ABSTRACT Cell physiology is impaired before protein aggregation and this may be more relevant than inclusions themselves for neurodegeneration. The present study aimed to characterize an animal model to enable the analysis of the cell biology before and after protein aggregation. Ten-month-old Lewis rats were exposed either to 1 or 2 mg/kg/day of rotenone, delivered subcutaneously through mini-pumps, for one month. Hyperphosphorylated TAU, alpha-synuclein, amyloid-beta peptide and protein carbonylation (indicative of oxidative stress) were evaluated in the hippocampus, substantia nigra and locus coeruleus through immunohistochemistry or western blot. It was found that 2 mg/kg/day rotenone increased amyloid-beta peptide, hyperphosphorylation of TAU and alpha-synuclein. Rotenone at 1mg/kg/day did not alter protein levels. Protein carbonylation remained unchanged. This study demonstrated that aged Lewis rats exposed to a low dose of rotenone is a useful model to study cellular processes before protein aggregation, while the higher dose makes a good model to study the effects of protein inclusions.


RESUMO A fisiologia celular está prejudicada antes da agregação proteica podendo ser mais importante para a neurodegeneração do que as próprias inclusões. Assim, o objetivo deste estudo é caracterizar um modelo animal para analisar os mecanismos e efeitos da agregação proteica. Ratos Lewis com 10 meses de idade foram expostos a rotenona (1 ou 2 mg/kg/dia), administrada subcutaneamente, utilizando minibombas osmóticas. Os níveis de peptídeo beta-amiloide, TAU hiperfosforilada, alfa-sinucleína e proteínas carboniladas (indicativo de estresse oxidativo) foram avaliados por imunohistoquímica e western blot no hipocampo, substância negra e locus coeruleus. Foi demonstrado que 2 mg/kg/dia de rotenona promoveu aumento do peptídeo beta-amiloide, hiperfosforilação da TAU e alfa-sinucleína. Já 1 mg/kg/dia de rotenona não alterou os níveis dessas proteína nessas regiões. As proteínas carboniladas não se alteraram. Foi demonstrado que ratos Lewis idosos expostos a baixas doses de rotenona são modelo de estudo dos processos celulares antes da agregação proteica, enquanto 2 mg/kg/dia de rotenona permite estudos sobre os efeitos da agregação proteica.


Assuntos
Animais , Masculino , Rotenona/administração & dosagem , Sistema Nervoso Central/efeitos dos fármacos , Sistema Nervoso Central/patologia , Modelos Animais de Doenças , Agregação Patológica de Proteínas/induzido quimicamente , Agregação Patológica de Proteínas/patologia , Ratos Endogâmicos Lew , Substância Negra/efeitos dos fármacos , Imuno-Histoquímica , Sistema Nervoso Central/metabolismo , Western Blotting , Reprodutibilidade dos Testes , Peptídeos beta-Amiloides/efeitos dos fármacos , Peptídeos beta-Amiloides/metabolismo , Estresse Oxidativo , alfa-Sinucleína/efeitos dos fármacos , alfa-Sinucleína/metabolismo , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia
5.
Arch. argent. pediatr ; 113(5): e260-e263, oct. 2015. ilus, tab
Artigo em Espanhol | LILACS | ID: lil-757066

RESUMO

El trauma ocular pediátrico es frecuente y es la principal causa de ceguera unilateral no congénita. La información en países en vías de desarrollo es escasa. El objetivo de esta serie de casos es describir las características clínicas y epidemiológicas del trauma ocular en niños menores de 14 años que consultaron al Hospital Dr. Rodolfo Robles Val verde en la Ciudad de Guatemala durante el año 2010. Se incluyeron 119 pacientes en el estudio. El género masculino en edad escolar (7-9 años) fue el más comprometido. El trauma más común fue el de globo cerrado. Los objetos más frecuentes causantes de la lesión fueron madera, juguetes y químicos. La vivienda fue el lugar donde más ocurrió el trauma. Se intervinieron 21 pacientes. Son necesarios programas de educación y prevención.


Pediatric ocular trauma is common and the leading cause of non congenital unilateral blindness. The information in developing countries is scarce. The objective of this case series is to describe clinical and epidemiological characteristics of ocular trauma in children under 14 years of age who visited Hospital Dr. Rodolfo Robles Valverde in Guatemala City in 2010. In this study 119 patients were included. School-aged (7-9 years) male gender was the most affected. Closed globe injury was the commonest. The most frequent objects causing the lesions were: wooden objects, toys and chemicals. Trauma occurred most frequently at home. Twenty one of the patients were surgically intervened. Education and prevention programs for pediatric ocular trauma are necessary.


Assuntos
Animais , Feminino , Masculino , Camundongos , Corpo Estriado/efeitos dos fármacos , Neurônios Dopaminérgicos/efeitos dos fármacos , Endossulfano/toxicidade , Inseticidas/toxicidade , Substância Negra/efeitos dos fármacos , Linhagem Celular Tumoral , Células Cultivadas , Sobrevivência Celular/efeitos dos fármacos , Corpo Estriado/metabolismo , Neurônios Dopaminérgicos/metabolismo , Intoxicação por MPTP , Neuroblastoma , Fatores Sexuais , Substância Negra/metabolismo
6.
Biomédica (Bogotá) ; 34(2): 207-217, abr.-jun. 2014. ilus, graf
Artigo em Inglês | LILACS | ID: lil-712403

RESUMO

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.


Assuntos
Animais , Masculino , Ratos , Corpo Estriado/efeitos dos fármacos , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios GABAérgicos/efeitos dos fármacos , Ácidos Heptanoicos/uso terapêutico , Infarto da Artéria Cerebral Média/tratamento farmacológico , Ataque Isquêmico Transitório/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Pirróis/uso terapêutico , Substância Negra/efeitos dos fármacos , Comportamento Animal , Corpo Estriado/irrigação sanguínea , Corpo Estriado/patologia , Avaliação Pré-Clínica de Medicamentos , Neurônios Dopaminérgicos/enzimologia , Neurônios Dopaminérgicos/patologia , Indução Enzimática/efeitos dos fármacos , Neurônios GABAérgicos/enzimologia , Neurônios GABAérgicos/patologia , Glutamato Descarboxilase/biossíntese , Glutamato Descarboxilase/genética , Ácidos Heptanoicos/farmacologia , Infarto da Artéria Cerebral Média/patologia , Ataque Isquêmico Transitório/patologia , Transtornos dos Movimentos/etiologia , Transtornos dos Movimentos/prevenção & controle , Proteínas do Tecido Nervoso/biossíntese , Proteínas do Tecido Nervoso/genética , Fármacos Neuroprotetores/farmacologia , Pirróis/farmacologia , Ratos Wistar , Recuperação de Função Fisiológica , Organismos Livres de Patógenos Específicos , Transtornos das Sensações/etiologia , Transtornos das Sensações/prevenção & controle , Substância Negra/irrigação sanguínea , Substância Negra/patologia , /biossíntese , /genética
8.
Braz. j. med. biol. res ; 45(1): 13-19, Jan. 2012. ilus, tab
Artigo em Inglês | LILACS | ID: lil-610548

RESUMO

Neonatal Sprague-Dawley rats were randomly divided into normal control, mild hypoxia-ischemia (HI), and severe HI groups (N = 10 in each group at each time) on postnatal day 7 (P7) to study the effect of mild and severe HI on anxiety-like behavior and the expression of tyrosine hydroxylase (TH) in the substantia nigra (SN). The mild and severe HI groups were exposed to hypoxia (8 percent O2/92 percent N2) for 90 and 150 min, respectively. The elevated plus-maze (EPM) test was performed to assess anxiety-like behavior by measuring time spent in the open arms (OAT) and OAT percent, and immunohistochemistry was used to determine the expression of TH in the SN at P14, P21, and P28. OAT and OAT percent in the EPM were significantly increased in both the mild (1.88-, 1.99-, and 2.04-fold, and 1.94-, 1.51-, and 1.46-fold) and severe HI groups (1.69-, 1.68-, and 1.87-fold, and 1.83-, 1.43-, and 1.39-fold, respectively; P < 0.05). The percent of TH-positive cells occupying the SN area was significantly and similarly decreased in both the mild (17.7, 40.2, and 47.2 percent) and severe HI groups (16.3, 32.2, and 43.8 percent, respectively; P < 0.05). The decrease in the number of TH-positive cells in the SN and the level of protein expression were closely associated (Pearson correlation analysis: r = 0.991, P = 0.000 in the mild HI group and r = 0.974, P = 0.000 in the severe HI group) with the impaired anxiety-like behaviors. We conclude that neonatal HI results in decreased anxiety-like behavior during the juvenile period of Sprague-Dawley rats, which is associated with the decreased activity of TH in the SN. The impairment of anxiety and the expression of TH are not likely to be dependent on the severity of HI.


Assuntos
Animais , Feminino , Ratos , Ansiedade/metabolismo , Comportamento Animal/fisiologia , Hipóxia-Isquemia Encefálica/metabolismo , Neurônios/enzimologia , Substância Negra/enzimologia , /metabolismo , Animais Recém-Nascidos , Ansiedade/enzimologia , Hipóxia-Isquemia Encefálica/enzimologia , Imuno-Histoquímica , Ratos Sprague-Dawley , Índice de Gravidade de Doença , /análise
9.
Arq. neuropsiquiatr ; 69(6): 892-895, Dec. 2011. ilus, tab
Artigo em Inglês | LILACS | ID: lil-612627

RESUMO

In Brazil there is no systematic study on Transcranial Sonography (TCS), a neuroimaging method that depicts echogenic deep brain structures using ultrasound. OBJECTIVE: To establish the percentage of subjects with permissive temporal windows and to address the ability of TCS of the substantia nigra (SN) to distinguish parkinsonian patients in a Brazilian sample. METHOD: We performed TCS using the Acuson X300 (Siemens, Germany) in 37 individuals: 23 with Parkinson's disease (PD) and 14 healthy controls. RESULTS: 10.8 percent of subjects had insufficient temporal acoustic bone windows. SN echogenic areas were larger in patients (mean±SD, 0.31±0.08cm²) compared to controls (mean±SD, 0.17±0.02cm²). TCS accurately identified 88.2 percent of PD patients. CONCLUSION: A large proportion of Brazilians seem to be eligible for TCS. An expressive number of PD patients could be diagnosed by TCS based on an expanded SN echogenic area. However, the current data is preliminary and must be corroborated by larger studies.


No Brasil não há estudos sistemáticos sobre a Ultrassonografia Transcraniana (USTC), modalidade de neuroimagem que visualiza estruturas ecogênicas profundas do parênquima cerebral utilizando ultrassom. OBJETIVO: Determinar a porcentagem de indivíduos com janelas ósseas adequadas e a capacidade da USTC da substância negra (SN) de discernir pacientes parkinsonianos em amostra brasileira. MÉTODO: USTC realizada com equipamento AcusonX300 (Siemens, Germany) em 37 indivíduos: 23 com doença de Parkinson (DP) e 14 controles saudáveis. RESULTADOS: 10,8 por cento dos participantes apresentaram janelas acústicas temporais inadequadas. As áreas de ecogenicidade da SN foram maiores nos pacientes (média±desvio padrão, 0,31±0,08 cm²) do que nos controles (média±desvio padrão, 0,17±0,02 cm²). A USTC identificou 88,2 por cento dos pacientes com DP. CONCLUSÃO: Grande proporção de brasileiros parece ser elegível para a realização de USTC. Um número expressivo dos pacientes com DP poderia ser diagnosticado com base no aumento da área ecogênica da SN. Contudo, esses dados preliminares devem ser corroborados com amostra mais numerosa.


Assuntos
Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson , Substância Negra , Ultrassonografia Doppler Transcraniana , Brasil , Estudos de Casos e Controles , Estudos Transversais , Projetos Piloto , Sensibilidade e Especificidade
10.
Rev. méd. Chile ; 139(1): 54-59, ene. 2011. ilus
Artigo em Espanhol | LILACS | ID: lil-595265

RESUMO

Background: The detection of hyperechogenicity of the substantia nigra using trans cranial sonography can bepredictive ofthe diagnosis of Parkinson Disease. Aim: To report an experience with transcranial sonography for the diagnosis of Parkinson disease. Material ana Methods: One hundred sixteen patients with movement disorders were subjected to a transcranial sonograpy to detect the presence ofhyper-chogenicity of the substantia nigra and basal ganglia. Afterwards, two physicians, unaware ofthe results ofthe sonography, examined the patients and reached a clinical diagnosis. The concordance between ultrasound results and the clinical diagnosis was analyzed. Results: In 64 patients, a clinical diagnosis of Parkinson disease was reached. Ofthese, 52 patients had substantia nigra hyperechogenicity and in 12, it was normal. On the other hand ultrasound was normal in 42 of43 patients without a clinical diagnosis of Parkinson disease. Therefore the sensitivity and specificity of trans cranial ultrasound for the diagnosis of Parkinson disease was 81 and 97 percent, res-pectively. Conclusions: Transcranial sonography has agood sensitivity and specificity for the diagnosis of Parkinson disease.


Assuntos
Humanos , Doença de Parkinson , Substância Negra , Ultrassonografia Doppler Transcraniana/métodos , Estudos de Coortes , Sensibilidade e Especificidade
11.
Braz. j. med. biol. res ; 43(11): 1047-1053, Nov. 2010. ilus
Artigo em Inglês | LILACS | ID: lil-564137

RESUMO

7-Nitroindazole (7-NI) inhibits neuronal nitric oxide synthase in vivo and reduces l-DOPA-induced dyskinesias in a rat model of parkinsonism. The aim of the present study was to determine if the anti-dyskinetic effect of 7-NI was subject to tolerance after repeated treatment and if this drug could interfere with the priming effect of l-DOPA. Adult male Wistar rats (200-250 g) with unilateral depletion of dopamine in the substantia nigra compacta were treated with l-DOPA (30 mg/kg) for 34 days. On the 1st day, 6 rats received ip saline and 6 received ip 7-NI (30 mg/kg) before l-DOPA. From the 2nd to the 26th day, all rats received l-DOPA daily and, from the 27th to the 34th day, they also received 7-NI before l-DOPA. Animals were evaluated before the drug and 1 h after l-DOPA using an abnormal involuntary movement scale and a stepping test. All rats had a similar initial motor deficit. 7-NI decreased abnormal involuntary movement induced by l-DOPA and the effect was maintained during the experiment before 7-NI, median (interquartile interval), day 26: 16.75 (15.88-17.00); day 28: 0.00 (0.00-9.63); day 29: 13.75 (2.25-15.50); day 30: 0.5 (0.00-6.25); day 31: 4.00 (0.00-7.13), and day 34: 0.5 (0.00-14.63), Friedman followed by Wilcoxon test,vs day 26, P < 0.05;. The response to l-DOPA alone was not modified by the use of 7-NI before the first administration of the drug (l-DOPA vs time interaction, F1,10 = 1.5, NS). The data suggest that tolerance to the anti-dyskinetic effects of a neuronal nitric oxide synthase inhibitor does not develop over a short-term period of repeated administration. These observations open a possible new therapeutic approach to motor complications of chronic l-DOPA therapy in patients with Parkinson’s disease.


Assuntos
Animais , Masculino , Ratos , Antidiscinéticos/uso terapêutico , Discinesia Induzida por Medicamentos/tratamento farmacológico , Inibidores Enzimáticos/uso terapêutico , Indazóis/uso terapêutico , Óxido Nítrico Sintase/antagonistas & inibidores , Corpo Estriado/efeitos dos fármacos , Modelos Animais de Doenças , Levodopa/farmacologia , Ratos Wistar , Substância Negra/efeitos dos fármacos
12.
Braz. j. med. biol. res ; 43(1): 85-95, Jan. 2010. ilus
Artigo em Inglês | LILACS | ID: lil-535638

RESUMO

The objective of the present study was to determine whether lesion of the subthalamic nucleus (STN) promoted by N-methyl-D-aspartate (NMDA) would rescue nigrostriatal dopaminergic neurons after unilateral 6-hydroxydopamine (6-OHDA) injection into the medial forebrain bundle (MFB). Initially, 16 mg 6-OHDA (6-OHDA group) or vehicle (artificial cerebrospinal fluid - aCSF; Sham group) was infused into the right MFB of adult male Wistar rats. Fifteen days after surgery, the 6-OHDA and SHAM groups were randomly subdivided and received ipsilateral injection of either 60 mM NMDA or aCSF in the right STN. Additionally, a control group was not submitted to stereotaxic surgery. Five groups of rats were studied: 6-OHDA/NMDA, 6-OHDA/Sham, Sham/NMDA, Sham/Sham, and Control. Fourteen days after injection of 6-OHDA, rats were submitted to the rotational test induced by apomorphine (0.1 mg/kg, ip) and to the open-field test. The same tests were performed again 14 days after NMDA-induced lesion of the STN. The STN lesion reduced the contralateral turns induced by apomorphine and blocked the progression of motor impairment in the open-field test in 6-OHDA-treated rats. However, lesion of the STN did not prevent the reduction of striatal concentrations of dopamine and metabolites or the number of nigrostriatal dopaminergic neurons after 6-OHDA lesion. Therefore, STN lesion is able to reverse motor deficits after severe 6-OHDA-induced lesion of the nigrostriatal pathway, but does not protect or rescue dopaminergic neurons in the substantia nigra pars compacta.


Assuntos
Animais , Masculino , Ratos , Dopamina/fisiologia , Atividade Motora/efeitos dos fármacos , Neurônios/patologia , Doença de Parkinson Secundária/patologia , Substância Negra/citologia , Núcleo Subtalâmico/lesões , Imuno-Histoquímica , Atividade Motora/fisiologia , N-Metilaspartato , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Veículos Farmacêuticos , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/fisiopatologia , Distribuição Aleatória , Ratos Wistar , Substância Negra/fisiopatologia , Núcleo Subtalâmico/efeitos dos fármacos , Núcleo Subtalâmico/patologia , Núcleo Subtalâmico/cirurgia , /metabolismo
13.
Rio de Janeiro; s.n; 2010. 106 p. ilus.
Tese em Português | LILACS | ID: lil-695616

RESUMO

A hipóxia isquemia (HI) pré-natal é uma das principais causas de mortalidade e doenças neurológicas crônicas em neonatos, que podem apresentar déficits remanentes como: retardamento, paralisia cerebral, dificuldade de aprendizado ou epilepsia. Estes prejuízos, provavelmente, estão relacionados com o atraso no desenvolvimento neural, astrogliose e com a perda de neurônios e oligodendrócitos. Déficits funcionais e cognitivos estão associados à degeneração de vias dopaminérgicas e de estruturas hipocampais. A enzima tirosina hidroxilase (TH) é a enzima limitante na síntese de dopamina e seus níveis são alterados em eventos de HI. O óxido nítrico (NO) é um gás difusível que atua modulando diferentes sistemas, participando de eventos como plasticidade sináptica e neuromodulação no sistema nervoso central e é produzido em grandes quantidades em eventos de injúria e inflamação, como é o caso da HI. O presente estudo teve por objetivos avaliar, utilizando o modelo criado por Robinson e colaboradores em 2005, os efeitos da HI sobre o comportamento motor e avaliar o desenvolvimento de estruturas encefálicas relacionadas a este comportamento como a substância negra (SN) e o complexo hipocampal. A HI foi induzida a partir do clampeamento das artérias uterinas da rata grávida, por 45 minutos no décimo oitavo dia de gestação (grupo HI). Em um grupo de fêmeas a cirurgia foi realizada, mas não houve clampeamento das artérias (grupo SHAM). A avaliação do comportamento motor foi realizada com os testes ROTAROD e de campo aberto em animais de 45 dias. Os encéfalos foram processados histologicamente nas idades de P9, P16, P23 e P90, sendo então realizada imunohistoquímica para TH e histoquímica para NADPH diaforase (NADPH-d), para avaliação do NO. Nossos resultados demonstraram redução da imunorreatividade para a TH em corpos celulares na SN aos 16 dias no grupo HI e aumento na imunorreatividade das fibras na parte reticulada aos 23 dias, com a presença de corpos celulares...


Perinatal hypoxia-ischemia (HI) is one of the major causes of mortality and chronic neurological diseases in newborns that can show permanent effects such as mental retardation, cerebral palsy, learning difficulty and epilepsy. It is probable that these impairs may be related to a delay in the neural development, astrogliosis and to the death of neurons and oligodendrocytes. Cognitive and functional deficits are related to degeneration of dopaminergic pathways and hippocampus. The enzyme tyrosine hydroxylase (TH) is a limiting step in the dopamine synthesis and its levels are impaired in HI insults. Nitric oxide (NO) is a diffusible gas that acts by modulating different systems and participates in several phenomena such as synaptic plasticity and neuromodulation in the central nervous system and is produced in higher levels in events of injury and inflamation as in the case of HI. This study aimed to evaluate the effects of HI on the motor behavior and to evaluate the development of brain structures related to this behavior as the substantia nigra (SN) and the hippocampal complex, using the model developed by Robinson and colleagues in 2005. HI was induced by clamping the uterine arteries of pregnant rats, for 45 minutes, on the eighteenth day of gestation (group HI). In a group of females, the surgery was performed, but no clamping of the arteries (group SHAM) was made. Assessment of motor behavior was performed with the ROTAROD test and open field test in animals of 45 days (P45) of age. The brains were processed histologically at ages P9, P16, P23 and P90, and then submitted to immunohistochemistry for TH and NADPH diaphorase (NADPH-d) histochemistry for evaluation of NOS. Our results demonstrated an apparent decrease in TH immunoreactivity in cell bodies in the SN at P16 in the HI group and an increase in immunoreactivity of the fibers in the SN pars reticulata at P23 with the presence of TH immunoreactive cell bodies at this same region in the HI group...


Assuntos
Animais , Feminino , Ratos , Hipóxia-Isquemia Encefálica/complicações , Atividade Motora/fisiologia , Hipocampo , Hipóxia Fetal/complicações , NADPH Desidrogenase , Óxido Nítrico/metabolismo , Substância Negra , Sistema Nervoso Central/lesões , Teste de Desempenho do Rota-Rod/métodos
14.
Braz. j. med. biol. res ; 41(10): 920-925, Oct. 2008. ilus, graf
Artigo em Inglês | LILACS | ID: lil-496807

RESUMO

Dopaminergic neurotransmission is involved in the regulation of sleep. In particular, the nigrostriatal pathway is an important center of sleep regulation. We hypothesized that dopaminergic neurons located in substantia nigra pars compacta (SNpc) could be activated by gentle handling, a method to obtain sleep deprivation (SD). Adult male C57/BL6J mice (N = 5/group) were distributed into non-SD (NSD) or SD groups. SD animals were subjected to SD once for 1 or 3 h by gentle handling. Two experiments were performed. The first determined the activation of SNpc neurons after SD, and the second examined the same parameters after pharmacologically induced dopaminergic depletion using intraperitoneal reserpine (2 mg/kg). After 1 or 3 h, SD and NSD mice were subjected to motor evaluation using the open field test. Immediately after the behavioral test, the mice were perfused intracardially to fix the brain and for immunohistochemical analysis of c-Fos protein expression within the SNpc. The open field test indicated that SD for 1 or 3 h did not modify motor behavior. However, c-Fos protein expression was increased after 1 h of SD compared with the NSD and 3-h SD groups. These immunohistochemistry data indicate that these periods of SD are not able to produce dopaminergic supersensitivity. Nevertheless, the increased expression of c-Fos within the SNpc suggests that dopaminergic nigral activation was triggered by SD earlier than motor responsiveness. Dopamine-depleted mice (experiment 2) exhibited a similar increase of c-Fos expression compared to control animals indicating that dopamine neurons are still activated in the 1-h SD group despite the exhaustion of dopamine. This finding suggests that this range (2-5-fold) of neuronal activation may serve as a marker of SD.


Assuntos
Animais , Masculino , Camundongos , Dopamina/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Privação do Sono/metabolismo , Substância Negra/metabolismo , Imuno-Histoquímica , Atividade Motora/fisiologia , Reserpina/farmacologia , Fatores de Tempo
15.
Prensa méd. argent ; 94(8): 453-468, oct. 2007. ilus
Artigo em Espanhol | LILACS | ID: lil-497128

RESUMO

Luego del estudio de 43 pacientes con síndromes extrapiramidales (Parkinsonismos, Temblor esencial, Parálisis Supranuclear) mediante evaluaciones clínicas, por Resonancia Magnética y ecografía transcraneana se perfeccionó la metodología de evaluación incluyendo el estudio sistematizado de la región mesencefálica (SN;T) Unidades de Intensidad ROI; Grado 2: 85-105 y Grado 1: 105-115, detección de depósitos férricos mediante técnica de GRE y correlacionarlo con la evaluación del área de sección transversal por eco transcraneano y la determinación de grados de visualización ecográfica del mesencéfalo...Lo anterior nos ha permitido incluir en nuestras evaluaciones rutinarias cuestionarios para evaluar olfato y conducta alimentaria, relacionados con las alteraciones del núcleo accumbens como marcadores tempranos de Enfermedad de Parkinson. Asimismo nos ha permitido diferenciar entre los distintos cuadros con afectación del circuito extrapiramidal.


Assuntos
Humanos , Dopamina/fisiologia , Doença de Parkinson/diagnóstico , Imageamento por Ressonância Magnética , Biomarcadores , Mutação/genética , Núcleo Accumbens , Norepinefrina/fisiologia , Substância Negra , Ubiquitina , Ultrassonografia
16.
Braz. j. med. biol. res ; 40(1): 89-96, Jan. 2007. ilus, graf
Artigo em Inglês | LILACS | ID: lil-439667

RESUMO

There is a great concern in the literature for the development of neuroprotectant drugs to treat Parkinson's disease. Since anesthetic drugs have hyperpolarizing properties, they can possibly act as neuroprotectants. In the present study, we have investigated the neuroprotective effect of a mixture of ketamine (85 mg/kg) and xylazine (3 mg/kg) (K/X) on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 6-hydroxydopamine (6-OHDA) rat models of Parkinson's disease. The bilateral infusion of MPTP (100 æg/side) or 6-OHDA (10 æg/side) into the substantia nigra pars compacta of adult male Wistar rats under thiopental anesthesia caused a modest (~67 percent) or severe (~91 percent) loss of tyrosine hydroxylase-immunostained cells, respectively. On the other hand, an apparent neuroprotective effect was observed when the rats were anesthetized with K/X, infused 5 min before surgery. This treatment caused loss of only 33 percent of the nigral tyrosine hydroxylase-immunostained cells due to the MPTP infusion and 51 percent due to the 6-OHDA infusion. This neuroprotective effect of K/X was also suggested by a less severe reduction of striatal dopamine levels in animals treated with these neurotoxins. In the working memory version of the Morris water maze task, both MPTP- and 6-OHDA-lesioned animals spent nearly 10 s longer to find the hidden platform in the groups where the neurotoxins were infused under thiopental anesthesia, compared to control animals. This amnestic effect was not observed in rats infused with the neurotoxins under K/X anesthesia. These results suggest that drugs with a pharmacological profile similar to that of K/X may be useful to delay the progression of Parkinson's disease.


Assuntos
Animais , Masculino , Ratos , Anestésicos Combinados/administração & dosagem , Ketamina/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Substância Negra/efeitos dos fármacos , Xilazina/administração & dosagem , Anestésicos Combinados/farmacologia , Monoaminas Biogênicas/metabolismo , Corpo Estriado/metabolismo , Modelos Animais de Doenças , Imuno-Histoquímica , Ketamina/farmacologia , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Fármacos Neuroprotetores/farmacologia , Oxidopamina , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Ratos Wistar , Substância Negra/metabolismo , Substância Negra/patologia , Tiopental/administração & dosagem , Tiopental/farmacologia , /metabolismo , Xilazina/farmacologia
18.
Braz. j. med. biol. res ; 37(4): 539-548, Apr. 2004. ilus, tab, graf
Artigo em Inglês | LILACS | ID: lil-357114

RESUMO

Parkinson's disease, a major neurodegenerative disorder in humans whose etiology is unknown, may be associated with some environmental factors. Nocardia otitidiscaviarum (GAM-5) isolated from a patient with an actinomycetoma produced signs similar to Parkinson's disease following iv injection into NMRI mice. NMRI mice were infected intravenously with a non-lethal dose of 5 x 10(6) colony forming units of N. otitidiscaviarum (GAM-5). Fourteen days after bacterial infection, most of the 60 mice injected exhibited parkinsonian features characterized by vertical head tremor, akinesia/bradykinesia, flexed posture and postural instability. There was a peak of nocardial growth in the brain during the first 24 h followed by a decrease, so that by 14 days nocardiae could no longer be cultured. At 24 h after infection, Gram staining showed nocardiae in neurons in the substantia nigra and occasionally in the brain parenchyma in the frontal and parietal cortex. At 21 days post-infection, tyrosine hydroxylase immunolabeling showed a 58 percent reduction of tyrosine hydroxylase in the substantia nigra, and a 35 percent reduction of tyrosine hydroxylase in the ventral tegmental region. Dopamine levels were reduced from 110 ± 32.5 to 58 ± 16.5 ng/mg protein (47.2 percent reduction) in brain from infected mice exhibiting impaired movements, whereas serotonin levels were unchanged (191 ± 44 protein in control and 175 ± 39 ng/mg protein in injected mice). At later times, intraneuronal inclusion bodies were observed in the substantia nigra. Our observations emphasize the need for further studies of the potential association between Parkinson's disease or parkinsonism-like disease and exposure to various nocardial species.


Assuntos
Humanos , Animais , Feminino , Camundongos , Encéfalo , Nocardia , Nocardiose , Doença de Parkinson , Encéfalo , Imuno-Histoquímica , Nocardiose , Doença de Parkinson , Organismos Livres de Patógenos Específicos , Substância Negra , Tirosina 3-Mono-Oxigenase
19.
Arq. neuropsiquiatr ; 61(4): 936-941, Dec. 2003. ilus, tab
Artigo em Inglês | LILACS | ID: lil-352429

RESUMO

A male 70 years old patient with diffuse or ''pure'' Lewy body disease is described. The diagnosis was made based on clinical features of nightmares with no atonia, attention deficits with fluctuation in cognitive function, incapacity to find his way around the neighbourhood and other formerly familiar environments and mild neuropsychiatric symptoms. Neuropsychological assessment showed memory deficits, visuospatial and visuo-constructive disturbances. He had neither parkinsonism nor recurrent visual hallucinations typically well formed and detailled. Neuroimaging (computed tomography and magnetic resonance spectroscopy) showed mild diffuse cortical atrophy, mostly on the left temporal lobe and a decrease of N-acetil-aspartate levels. A cholinesterase inhibitor was prescribed to this patient during 6 months with clinically relevant behavioral effect. Diagnosis confirmation was made by post-mortem neuropathological findings. Macroscopical features were mild atrophy on the frontal, parietal and temporal lobes, notedly on the frontal lobes. Microscopically, there was neuronal loss and diffuse classic Lewy bodies. Brainstem (substantia nigra, raphe nucleus, locus coeruleus, pedunculopontine nucleus), limbic cortex, and neocortex (frontal, parietal and temporal) were the areas of predilection for Lewy bodies. Hematoxylin-eosin and Bielschowsky staining did not show neuronal swelling (balooned cell), argyrophilic inclusion (Pick's bodies), neurofibrillary tangles nor senile plaques. Immunohistochemical staining for anti-tau, anti-beta-amyloid, and anti-prion protein were negative. Antiubiquitine reaction was positive for Lewy body in the cerebral cortex and brainstem


Assuntos
Humanos , Masculino , Idoso , Sonhos/psicologia , Doença por Corpos de Lewy/patologia , Atrofia , Carbamatos/uso terapêutico , Inibidores da Colinesterase/uso terapêutico , Evolução Fatal , Imuno-Histoquímica , Doença por Corpos de Lewy/tratamento farmacológico , Doença por Corpos de Lewy/psicologia , Espectroscopia de Ressonância Magnética , Testes Neuropsicológicos , Neurônios/patologia , Substância Negra/patologia , Tomografia Computadorizada por Raios X
20.
Arq. neuropsiquiatr ; 61(2B): 381-386, Jun. 2003. ilus
Artigo em Português | LILACS | ID: lil-342780

RESUMO

Apresentamos 5 casos de parkinsonismo nos quais as imagens de ressonância magnética (RM) mostram alterações em estruturas do circuito dos núcleos da base (NB). Foram estudados 5 pacientes: 3 do sexo masculino e 2 do feminino nos quais as manifestações clínicas tiveram início nas faixas estárias de 5 a 52 anos. Os exames de RM foram realizados com equipamento de 1.5T. As imagens nas sequências em T2 evidenciaram hipersinal bilateral e simétrico nas seguintes topografias: exclusivamente na substância negra (3 casos), exclusivamente no globo pálido (1 caso) e envolvendo simultaneamente a substância negra, o globo pálido e as conexöes nigro-estriatais (1 caso). Em três casos havia dados sugestivos de parkinsonismo secundário: um pelo herbicida glifosato; outro após vacinaçäo anti-sarampo; outro após período de coma por encefalite. Nos dois casos restantes, o diagnóstico clínico era de doença de Parkinson (DP). Entretanto, nesses dois casos, os dados da RM permitiram excluir o diagnóstico inicial de DP. A RN foi fundamental para identificar casos de parkinsonismo secundário, embora em alguns destes pacientes näo tenha sido possível determinar os agentes etiológicos


Assuntos
Adolescente , Adulto , Feminino , Pré-Escolar , Humanos , Transtornos Parkinsonianos , Gânglios da Base , Imageamento por Ressonância Magnética , Transtornos Parkinsonianos , Gravidez , Estudos Retrospectivos , Substância Negra
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