RESUMO
Early degeneration of pedunculopontine nucleus (PPN) is considered part of changes that characterize premotor stages of Parkinson's disease (PD). In this paper, the effects of unilateral neurotoxic lesion of the PPN in motor execution and in the development of oxidative stress events in striatal and nigral tissues in rats were evaluated. The motor performance was assessed using the beam test (BT) and the cylinder test (CT). Nigral and striatal redox balance, was studied by means of biochemical indicators such as malondialdehyde (MDA), nitric oxide (NO) and the catalase enzymatic activity (CAT EA). Lesioned rats showed fine motor dysfunction expressed both as an increase in the length (p<0.001) and deviation (p<0.001) of the traveled path and also in the time spent (p<0.01) in the circular small beam (CBS) (p<0.01) in comparison with control groups. In addition, the lesioned rats group presented a right asymmetry index greater than 0.5 which is consistent with a significant increase in the percentage of use of the right forelimb (ipsilateral to the lesion), compared with the control group (p<0.05). Biochemical studies revealed that after 48-h PPN neurotoxic injury, the CAT EA showed a significant increase in the subtantia nigra pars compacta (SNpc) (p<0.05). This significant increase of CAT EA persisted in the nigral tissue (p<0.001) and reached the striatal tissue (p<0.001) seven days after PPN injury. Also at seven days post-injury PPN, increased concentrations of MDA (p<0.01) and a tendency to decrease in the concentrations of NO in both structures (SNpc and striatum) were found. The events associated with the generation of free radicals at nigral and striatal levels, can be part of the physiological mechanisms underlying motor dysfunction in rats with unilateral PPN neurotoxic lesion.
Assuntos
Corpo Estriado/fisiologia , Atividade Motora/fisiologia , Núcleo Tegmental Pedunculopontino/fisiopatologia , Equilíbrio Postural/fisiologia , Substância Negra/fisiologia , Animais , Catalase/metabolismo , Agonistas de Aminoácidos Excitatórios/toxicidade , Membro Anterior/fisiopatologia , Lateralidade Funcional , Masculino , Malondialdeído/metabolismo , Transtornos dos Movimentos/fisiopatologia , N-Metilaspartato/toxicidade , Óxido Nítrico/metabolismo , Oxirredução , Estresse Oxidativo/fisiologia , Núcleo Tegmental Pedunculopontino/efeitos dos fármacos , Núcleo Tegmental Pedunculopontino/patologia , Ratos WistarRESUMO
Brain-derived neurotrophic factor (BDNF) concentration was measured in the striatum and cortex after quinolinic acid intrastriatal lesion and transplantation of bone marrow cells (BMSC). The results showed a significant increase of the BDNF levels in the striatum and cortex of the lesioned animals and the ability of the transplanted cells to increase the levels of BDNF in both sites. This recovery of BDNF production and distribution might have beneficial effects and ameliorate the negative consequences of the striatal lesion, a mechanism of potential interest for the treatment of Huntington's disease (HD).
Assuntos
Transplante de Medula Óssea/métodos , Fator Neurotrófico Derivado do Encéfalo/biossíntese , Ácido Quinolínico/toxicidade , Animais , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Córtex Cerebral/cirurgia , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Corpo Estriado/cirurgia , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
INTRODUCTION: Transplant is one of the alternatives available for the treatment of neurodegenerative diseases aimed at replacing the cells lost during the course of the disease. One promising source of cells for the development of transplants could be the mononucleate cells from bone marrow. AIMS. The purpose of this study was to study the capacity of bone marrow mononucleate cells to survive the transplant process, and to search for a method that enables tracking of these cells in vivo once they have been implanted. MATERIALS AND METHODS: Bone marrow mononucleate cells were extracted from the femur of rats by means of a Ficoll-Hypaque gradient. The cells under study were modified genetically with an adenovirus that expresses the PFV or which are marked with Hoechst dye. The marked cells were implanted in the striatum of rats with lesions caused by quinolinic acid. RESULTS: The viability of the genetically modified cells was low, whereas that of the cells marked with Hoechst dye was above 90%. The implanted cells survived the transplant at least a month and dispersed away from the site of entry towards the corpus callosum and cortex. CONCLUSIONS: We consider that the use of Hoechst dye offers more advantages for tracking these cells in vivo. Mononucleate cells have a number of characteristics that allow them to be included as candidate sources of cells for the treatment of neurodegenerative diseases.
Assuntos
Células da Medula Óssea , Transplante de Medula Óssea , Sobrevivência Celular , Ácido Quinolínico/toxicidade , Córtex Visual , Animais , Benzimidazóis/metabolismo , Células da Medula Óssea/citologia , Células da Medula Óssea/fisiologia , Movimento Celular , Corantes Fluorescentes/metabolismo , Masculino , Doenças Neurodegenerativas/terapia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Córtex Visual/citologia , Córtex Visual/efeitos dos fármacos , Córtex Visual/patologiaRESUMO
OBJECTIVE: Clinical and experimental data support the role of immune mechanisms in the pathogeny of epilepsy. The purpose of this work was to study the immunological aspects in 30 epileptic patients with complex partial crisis resistant to antiepileptic drugs. PATIENTS AND METHODS: The patients were evaluated by EEG-Video and they were grouped attending to epileptogenic focus localization in: temporals (n = 16), lateralized (n = 6) and extratemporals (n = 4). We also studied a group with psychogenic epilepsy (n = 4), this group was diagnosed after EEG-video evaluation. The following immunological evaluations has been carried out: levels of serum immunoglobulins (IgG, IgM e IgA) by radial immunodiffusion test and lymphocytic subpopulations using immunocytochemical methods. We measured the percent of T and B lymphocytes (CD3 and CD20), helper/inductor lymphocyte T (CD4), suppressor/cytotoxic (CD8), interleukine-2 receptor (CD25) and human leukocyte antigen (HLA-DR). RESULTS: The results show a significant increase of CD8+ lymphocytes (p < 0.05) and in the activation markers (CD25+ and HLA-DR+ cells). The evaluation of immunological parameters applied to different group of epileptogenic focus localization shown that the increase of CD8+ lymphocytes is limited to temporal and lateralized patients (p < 0.01). The patients with extratemporal localization of focus and the psychogenic cases shown normal values for the evaluated immunological lymphocyte markers. We did not find a deficit in the humoral immunological aspects. CONCLUSIONS: Taking into account that patients diagnosed as psychogenic received an antiepileptic drug treatment identical to that of the other group, the observed immunological changes might be related with the patogeny of certain epilepsy variants associated with the focus localization and not with the medication.
Assuntos
Epilepsia/imunologia , Epilepsia/fisiopatologia , Doenças do Sistema Imunitário/fisiopatologia , Adulto , Antígenos de Superfície/metabolismo , Eletroencefalografia , Epilepsia/classificação , Epilepsia/diagnóstico , Feminino , Humanos , Imunoglobulinas/sangue , Subpopulações de Linfócitos , Masculino , Gravação em VídeoRESUMO
INTRODUCTION: Several studies that has focused to the dopaminergic transmission in the basal ganglia in parkinsonian condition, but only a few article has taking into account the imbalance between dopaminergic and cholinergic transmission. OBJECTIVE: To evaluate the muscarinic cholinergic receptors density in SNc and PPN in the 6-OHDA model. MATERIALS AND METHODS: Were organized five experimental groups in correspondence to the place of the lesion: I. Non treated rats, II. 6-OHDA lesion in SNc, III. 6-OHDA lesion in SNc + quinolinic acid lesion in NST, IV. Sham operated rats, V. Quinolinic acid in STN. Were obtained coronal sections of 20 microm thickness of SNc and PPN from rats and in these sections was evaluated the muscarinic receptors density through autoradiographic technique with [3H]quinuclidinylbenzilate (QNB) (1.23 nM). The muscarinic antagonist atropine (1 microM) was utilized as non-specific union. The density was evaluated in both hemispheres and the density optical was converted in fentomolas/mg of tissue with base to values obtained from tritium standards. RESULTS: Significant diminution of the muscarinic receptors density was found in the SNc ipsilateral to the 6-OHDA lesion from experimental groups II (t=2.76; p<0.05) and III (t=4.06; p<0.05). In the group V, was seen a significant increase of muscarinic receptor density in the SNc ipsilateral to the 6-OHDA lesion. The comparison between experimental groups evidenced significant differences among them (F=13.13; p<0.001) with a significant decrease in the density from SNc of groups II and III and significant increase in the density from SNc of group V in comparison of the others groups. In relation to PPN, muscarinic receptors density from right PPN ipsilateral to the 6-OHDA lesion, shown significant differences (F=3.93; p<0.01) between the experimental groups with a significant increase of this variable in the group II. CONCLUSIONS: These results signal a modification of cholinergic activity after 6-OHDA lesion. The changes in the muscarinic receptors populations located in SNc and PPN could be part of different compensatory mechanisms to attempt ameliorate the imbalance between dopaminergic and cholinergic transmission that it was installed after denervation of nigrostriatal forebrain bundle. The excitotoxic lesion of STN impose a new adjust mechanism for cell from PPN, which could be expressed in the changes of muscarinic cholinergic receptors population at the level of SNc.
Assuntos
Gânglios da Base/química , Receptores Muscarínicos/análise , Substância Negra/química , Núcleo Subtalâmico/química , Animais , Autorradiografia , Masculino , Ratos , Ratos WistarRESUMO
INTRODUCTION: There is currently a growing interest for conducting studies into the electrical and neurochemical activity of the pedunculopontine nucleus (PPN) due to the privileged position occupied by this structure in the flow of information to and from the cortex. This nucleus acts as a relay, not only for the motor information that is processed in the basal ganglia but also for information of an emotional type, whose main centre is the nucleus accumbens. It is also strongly linked with the aspects that determine the mechanisms governing addiction to certain drugs. DEVELOPMENT: We conduct a detailed analysis of the main findings from studies of the role played by the PPN in the physiopathology of Parkinsonism, namely the study of metabolic activity, immunohistochemical studies with different tracers, electrophysiological studies that have confirmed the immunohistochemical observations, as well as deep electrical stimulation carried out in non human primates. Furthermore, we also examine the part played by this structure in the processing of emotional information associated with different learning tasks. CONCLUSIONS: Overall, the authors grant the PPN a privileged position in the physiopathology of the axial disorders related to Parkinson s disease; its most important afference, stemming from the subthalamic nucleus, appears to play a key role in the understanding of the part played by the PPN in Parkinsonism.
Assuntos
Emoções , Atividade Motora/fisiologia , Núcleo Tegmental Pedunculopontino/fisiologia , Animais , Humanos , Núcleo Accumbens/metabolismo , Doença de Parkinson/metabolismo , Doença de Parkinson/fisiopatologia , Núcleo Tegmental Pedunculopontino/anatomia & histologiaRESUMO
Bioethics , which provides a new ethical outlook on human life, is a term used in public health and biomedical research issues. It is for this reason that, in this paper, we decided to analyse certain aspects associated with the ethical considerations we must bear in mind when conducting research in humans, although the purpose of doing so is to cure or to improve the quality of life of people who suffer from certain diseases, many of which are fatal. Reasons are put forward to make it necessary to doubt which is the strategy with the most favourable benefit/risk relation for those who will undergo such interventions. We describe Alzheimer s disease and discuss the possible use of neurotrophic drugs in the treatment of this disorder (NGF therapy). We also emphasise the care that will have to be taken in each of the stages of development of the research. That is why we are witnessing the emergence of a new culture that is needed to regulate the multiple interventions that can be performed on life, and to guarantee the primacy of what is good, both for the human being of today and those of generations to come.
Assuntos
Temas Bioéticos , Fatores de Crescimento Neural/uso terapêutico , Adulto , Idoso , Doença de Alzheimer/tratamento farmacológico , Animais , Ensaios Clínicos como Assunto/ética , Ensaios Clínicos como Assunto/métodos , Ensaios Clínicos como Assunto/normas , Avaliação Pré-Clínica de Medicamentos , Tratamento Farmacológico/ética , Feminino , Experimentação Humana/ética , Humanos , Masculino , Pessoa de Meia-Idade , Fator de Crescimento Neural/efeitos adversos , Fator de Crescimento Neural/fisiologia , Fator de Crescimento Neural/uso terapêutico , Fatores de Crescimento Neural/efeitos adversos , Fatores de Crescimento Neural/fisiologia , Primatas , Qualidade de Vida , Roedores , SegurançaRESUMO
INTRODUCTION: Nerve growth factor (NGF) is the best characterized neurotrophic polypeptide. Initially it was postulated that alterations in the expression of NGF within its production sites may be responsible for the consistent atrophy and loss of cholinergic basal forebrain neurons in dementing illness such as Alzheimer s Disease (AD). OBJECTIVE: We analyze the NGF concentration in serum from control and patients with AD in order to elucidate something alteration in this fluid related with AD neuropathology. PATIENTS AND METHODS: We applied a twosite enzyme immunoassay to determine NGF levels in sera of patients with AD. RESULTS: Sera from Alzheimer s patients (36+/-7 pg/ml) showed slight but non significant reduction in NGF levels when compared with age related controls (66+/-18 pg/ml). On the another hand, the NGF concentrations in AD patients and control subjects to the sex were following: female AD patients showed a mean of 33.27+/-10.43 pg/ml vs 57.83+/-22 pg/ml founded in female controls, while the mean value for male AD patients was 40.87+/-12.29 pg/ml vs 37.47+/-12.28 pg/ml for the male controls. In all the cases studied, no significant differences were observed according to Student t-Test. CONCLUSIONS: Even when no significant differences were observed between controls and AD patients, the results show a tendency NGF concentration decrease in this illness. Certainly, NGF is produced not only in the forebrain but throughout the body, for this reason, more studies, including the analysis of cerebrospinal fluid would be useful to define the real relationship between NGF concentration changes in serum and AD-related changes in endogenous NGF concentrations, taking into account increasing levels by exogenous NGF administration could still be useful in maintaining the cholinergic neurons.
Assuntos
Doença de Alzheimer/metabolismo , Fator de Crescimento Neural/metabolismo , Prosencéfalo/metabolismo , Idoso , Método Duplo-Cego , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Fator de Crescimento Neural/sangue , Fator de Crescimento Neural/líquido cefalorraquidianoRESUMO
OBJECTIVES: In this study we review the major concepts related to the immunological aspects which have currently been shown to be, perhaps, one of the basic factors of the so called neuroimmune cascade which characterizes Alzheimer s disease (AD). We emphasise the mechanisms causing these alterations, their repercussions and implications in this disease. DEVELOPMENT: There is a close relationship between the nervous, immune and endocrine systems, due to the presence of molecules such as the interleukins which permit this connection, for example: the IL 1 and IL 6 are involved in the immunological events which occur in AD, in which it has been suggested that the cell damage and neurodegeneration which occurs may be due to a neuroimmune reaction together with inflammatory mechanisms. The World Health Organization (WHO) has estimated that in the coming years, the population affected will reach a total of 423 million persons aged over 65, including a prevalence of 13.9% of persons aged between 70 and 89 years with AD. CONCLUSIONS: It is necessary to have clear, precise, reliable knowledge of the neuroimmune mechanisms involved in AD, if we take into account that the quantitative determination of interleukins may be a key to the overall evaluation of patients with AD. It may also be a useful tool for the follow up of patients treated by a method of neuro restoration. This is useful when classifying each patient and will lead to a better quality of life.
Assuntos
Doença de Alzheimer/imunologia , Interleucina-1/metabolismo , Interleucina-6/metabolismo , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/fisiopatologia , Humanos , Interleucina-1/imunologia , Interleucina-6/imunologia , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Transthyretin is considered an excellent marker for monitoring nutritional status in serum. In cerebrospinal fluid it is synthesized by chroroid plexus. Cuban epidemic neuropathy is an emergent disease with a hypothetically viral and nutritional origin. OBJECTIVE: To know the behavior of this transport molecule in serum and cerebrospinal fluid in patients with Cuban epidemic neuropathy. PATIENTS AND METHODS: Serum and cerebrospinal fluid was quantified in 11 patients with Cuban epidemic neuropathy, eight patients suffering from other neuropathies and 15 patients with Down's syndrome and 10 patients with Alzheimer's disease. RESULTS: Serum transthyretin was diminished in patients with Cuban epidemic neuropathy, other neuropathies and Alzheimer's disease. Down's syndrome patients had significantly higher transthyretin levels in comparison with Cuban epidemic neuropathy and Alzheimer's disease. Cerebrospinal fluid transthyretin was significantly increased in patients with Cuban epidemic neuropathy in comparison with the normal values and with Alzheimer's disease patients whose values were settled below the normal values. CONCLUSIONS: The decrement of serum transthyretin in Cuban epidemic neuropathy indicates malnutrition and its higher levels in cerebrospinal fluid also indicate a viral infection. These findings support the nutrio-viral hypothesis of the disease.
Assuntos
Doenças do Sistema Nervoso/sangue , Doenças do Sistema Nervoso/líquido cefalorraquidiano , Pré-Albumina/análise , Adolescente , Adulto , Doença de Alzheimer/sangue , Doença de Alzheimer/líquido cefalorraquidiano , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Criança , Cuba , Síndrome de Down/sangue , Síndrome de Down/líquido cefalorraquidiano , Humanos , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/virologia , Pré-Albumina/líquido cefalorraquidianoRESUMO
INTRODUCTION: The neurotrophins are a family of proteins which are closely related structurally and functionally and include nerve growth factor (NGF), brain derived nerve factor (BDNF) and neurotrophin-3 (NT-3), neurotrophin-4/5 (NT-4/5) and more recently neurotrophin-6 (NT-6). BDNF is one of the most important endogenous proteins for control of survival, growth and differentiation of certain neurone populations both in the peripheral and central nervous systems. DEVELOPMENT: The ARNmt of the BDNF is found in nearly all regions of the brain. The highest levels are those of the hippocampus and cerebral cortex. The large number of effects attributed to BDNF are probably due to the union of this protein to its specific receptor on the cell surface, which leads to the formation of a complex which enables transmission of the signal caused by activation of the specific neurone pathway. Since discovery, BDNF has been detected and/or measured by different methods from biological assay to the application of molecular biology techniques. These methods have permitted analysis of the biochemical characteristics of this factor and its behaviour in different tissues. CONCLUSIONS: In this paper we review the most relevant aspects of distribution, biological actions of BDNF on different neurone populations, its clinical usefulness in neurological disorders, routes of administration and side effects.