RESUMO
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
BACKGROUND: Associations between electrophysiological and histological findings might provide an insight into the epileptogenicity of mild focal cortical dysplasia (FCD) in patients with temporal lobe epilepsy (TLE) and a dual pathology. SUBJECTS AND METHODS: A total of 22 patients with pharmacoresistant TLE were included in the study, 16 of them with histologically confirmed hippocampal sclerosis (HS) associated with neocortical temporal mild Palmini Type-I FCD subtypes and 6 with HS. Intraoperative electrocorticography (ECoG) recordings were analysed for epileptiform discharge frequency and morphology. Associations between histological, and electrocorticography pattern findings in these patients were analysed. Electroclinical outcomes in these patients were also evaluated. RESULTS: Neocortical areas with mild Palmini Type-I FCD showed a significantly higher spike frequency (SF) recorded in the inferior temporal gyrus than those neocortical areas in patients with HS. There was a tendency to higher spike frequency and lower amplitude in neocortical areas with histopathologic subtype IB FCD in relation with IA during intraoperative ECoG. Post-SF excision and amplitude were significantly lower during neocortical post-excision intraoperative ECoG than during neocortical pre-excision recording. There was no difference found in the clinical outcome between patients with and without FCD. CONCLUSIONS: Intraoperative electrocorticographic interictal spike frequency recorded in the neocortical inferior temporal gyrus may help to characterize the histopathologic subtypes of mild Palmini Type-I FCD in patients with temporal lobe epilepsy (TLE) and a dual pathology. Our data support the epileptogenicity of neocortical mild FCD in TLE and assessments of ECoG patterns are relevant to determine the extent of the resection in these patients which can influence the electroclinical outcome.
Assuntos
Eletroencefalografia/métodos , Epilepsia do Lobo Temporal/patologia , Epilepsia do Lobo Temporal/fisiopatologia , Malformações do Desenvolvimento Cortical/patologia , Neocórtex/patologia , Adolescente , Adulto , Lobectomia Temporal Anterior/métodos , Epilepsia do Lobo Temporal/cirurgia , Feminino , Seguimentos , Hipocampo/patologia , Humanos , Masculino , Malformações do Desenvolvimento Cortical/fisiopatologia , Malformações do Desenvolvimento Cortical/cirurgia , Pessoa de Meia-Idade , Neocórtex/fisiopatologia , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
INTRODUCTION: The dual pathology consisting of hippocampal sclerosis plus focal cortical dysplasia (FCD) is often reported in patients with medication-resistant medial temporal lobe epilepsy (MTLE). AIMS: To determine the histopathological changes that take place in the neocortex of patients with medication-resistant MTLE submitted to surgery and to evaluate the relation between the histopathological changes, pathological background and the clinical course of patients who had received surgical treatment. MATERIALS AND METHODS: Tissue obtained by en bloc resection from the neocortex of 18 patients with MTLE refractory to medical treatment was processed histologically and a tailored temporal lobectomy was performed with electrocorticography. RESULTS: Dual pathology was diagnosed in 13 patients (72.2%). Imaging studies confirmed the existence of mesial sclerosis of the temporal in 100% of cases and there was no evidence of neocortical lesions. Histologically, 46.15% and 38.46% of the patients were diagnosed as belonging to FCD type 1a and FCD type 1b, respectively. Only one patient presented FCD type 2a. A statistically significant relation was found between the presence of dual pathology and the existence of an early precipitating injury (p = 0.04). One year after surgery, 72.7% (8/11) patients with dual pathology were classified as belonging to Engel class I. CONCLUSIONS: In patients with MTLE there are microscopic FCD-type alterations in the neocortex. There is an association between these alterations and the existence of an initial precipitating injury. Complete resection of the epileptogenic area, which is guaranteed by the lobectomy tailored by electrocorticography, allows patients to enjoy a favourable post-surgical progression one year after surgery.
Assuntos
Epilepsia do Lobo Temporal/patologia , Epilepsia do Lobo Temporal/cirurgia , Neocórtex/patologia , Adulto , Resistência a Medicamentos , Epilepsia do Lobo Temporal/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: A good deal of evidence currently exists to show that transplanting foetal mesencephalic tissue can produce symptomatic benefits both in patients and in disease models. Nevertheless, the technical and ethical difficulties involved in obtaining enough suitable foetal cerebral tissue have been a serious obstacle to its application. Stromal cells derived from bone marrow, due to their potential capacity to generate different types of cells, could be an ideal source of material for cell restoration in neurodegenerative diseases. AIMS: Our aim was to evaluate the effect of transplanting stromal cells derived from bone marrow on the behaviour of 6-OHDA rats, when they are inserted into the striatum. MATERIAL AND METHODS: In this study we used rats with a lesion in the substantia nigra induced by 6-hydroxydopamine, divided into several experimental groups. Rotary activity induced by D-amphetamine (5 mg/kg, intraperitoneally) was evaluated before and throughout the three months following the transplant in all the experimental groups, except in the group of healthy controls. Hemiparkinsonian rats received a total of 350 000 foetal ventral mesencephalic cells and 8 x 10(4) stromal cells/microL, which were implanted in the striatum. RESULTS AND CONCLUSIONS: Animals with stromal cells transplanted in the body of the striatum significantly reduced the number of turns induced by amphetamine (p < 0.05); yet this reduction was not greater than that induced by foetal mesencephalic cell transplants. We were also unable to demonstrate any significant improvement in the motor skills of the forelimbs.
Assuntos
Modelos Animais de Doenças , Doença de Parkinson/cirurgia , Células Estromais/transplante , Animais , Comportamento Animal , Masculino , Oxidopamina/administração & dosagem , Doença de Parkinson/etiologia , Ratos , Ratos WistarRESUMO
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
AIMS: The purpose of this work was to gather the information currently available about the content of nerve growth factor (NGF) in experimental models of neurodegeneration and in neurodegenerative diseases, including Alzheimer's, Parkinson's and Huntington's diseases, as well as to analyse how NGF content is affected by the application of different neurorestorative therapies (transplant and trophic therapy) in these neurological entities. DEVELOPMENT: Neurotrophins are proteins that promote the differentiation, growth and survival of many populations of peripheral neurons and the central nervous system during development and adulthood. NGF is the best known and most widely researched member of this family, which is also made up of the growth factor derived from the brain and neurotrophins 3, 4/5, 6 and 7. In the last few decades, significant progress has been made in the knowledge available about the biological role played by these factors, their molecular characterisation and regulation, as well as their signalling mechanisms. Yet, little is known about the role played by the neurotrophic factors in neurodegenerative diseases or whether the levels of these factors are modified following the use of neurorestorative treatment. CONCLUSIONS: Neurodegenerative disorders, especially Parkinson and Alzheimer, are accompanied by modifications in the levels of NGF that depend on the extent to which the disease has progressed. A model of the changes in NGF content during neurodegenerative processes is also proposed.
Assuntos
Fator de Crescimento Neural/metabolismo , Fator de Crescimento Neural/uso terapêutico , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/metabolismo , Animais , Transplante de Células , Modelos Animais de Doenças , Progressão da Doença , Humanos , Fator de Crescimento Neural/genética , Regeneração Nervosa/fisiologia , Receptores de Fator de Crescimento Neural/metabolismoRESUMO
INTRODUCTION: The main strategy followed in neural transplants as a method of treatment for Parkinson s disease, both experimental and clinical, has been to introduce foetal mesencephalic cells into the target area: the striatum. However, when the dopaminergic cells in the substantia nigra degenerate, not only is the dopaminergic innervation of the striatum affected but also other nuclei: globus pallidus, substantia nigra, substantia nigra pars reticulata and subthalamic nucleus. A series of data from pharmacological and physiological studies offer strong evidence that the dopamine released in these nuclei may play an important role in regulating the output nuclei of the basal ganglia. AIM: To evaluate the effect of transplanting foetal mesencephalic cells on the behaviour of 6 OH DA rats when introduced into the striatum and the subthalamic nucleus. MATERIALS AND METHODS: 6 OH DA was used to induce lesions in the substantia nigra of rats, which were divided into several experimental groups. The rotating activity induced by D amphetamine (5 mg/kg, intraperitoneally) and apomorphine (0.05 mg/kg, subcutaneously) was evaluated before and three months after the transplant in all the experimental groups, except in the control group of healthy rats. The hemiparkinsonian rats received a total of 350,000 foetal ventral mesencephalic cells, which were implanted within small deposits in the striatum (8) and in the subthalamic nucleus (4). RESULTS AND CONCLUSIONS: Rotation induced by both drugs was significantly lower (p= 0.05) in animals that had had dopaminergic cells transplanted into the striatum body. No significant improvement in this behaviour was to be found when transplants were limited to just the subthalamus or, simultaneously, also to the striatum. A significant increase in rotating behaviour induced by apomorphine was observed in the group which received a transplant in just the subthalamus.
Assuntos
Transplante de Tecido Encefálico , Transplante de Tecido Fetal , Mesencéfalo/citologia , Neurônios/transplante , Doença de Parkinson/terapia , Núcleo Subtalâmico/cirurgia , Córtex Visual/cirurgia , Adrenérgicos/farmacologia , Animais , Antiparkinsonianos/farmacologia , Apomorfina/farmacologia , Comportamento Animal , Dextroanfetamina/farmacologia , Modelos Animais de Doenças , Dopamina/metabolismo , Masculino , Mesencéfalo/embriologia , Mesencéfalo/transplante , Neurônios/citologia , Neurônios/efeitos dos fármacos , Oxidopamina/toxicidade , Ratos , Ratos Wistar , Rotação , Núcleo Subtalâmico/patologia , Córtex Visual/patologiaRESUMO
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
INTRODUCTION: Alzheimer s disease (AD) is a progressive degenerative disease affecting a significant proportion of the elderly population. The disease is characterized clinically by a progressive loss of memory function and mental impairment associated with the presence of degenerative well known pathological lesions. Although, the pathogenesis of AD is unclear; several reports indicate the involvement of immune factors. PATIENTS AND METHODS: This paper evaluates some cerebrospinal fluid immune markers from 21 patients with early and late AD and 20 age matched non-demented subjects. The analytical method included the evaluation of T cell subpopulations (using AcMc CD2, CD4, CD8) and activated T cells (AcMc HLA-DR and CD25) from CSF and peripheral blood by immunocytochemical techniques on a fixed cell slide as described by Bernd. The lymphocyte phenotype expressed as a percentage of positively stained cells for each cell surface marker evaluated. RESULTS: Some significant differences were observed for T cell subpopulations from different compartments, between the different AD groups and the controls (p< 0.05). Nevertheless, the most significant differences were found in the activated T cells from cerebrospinal fluid between AD groups and controls (p< 0.01). CONCLUSIONS: These results support the theory of neuroimmune dysregulation, probably involved in the progressive neurodegeneration and dementia in some AD.
Assuntos
Doença de Alzheimer/epidemiologia , Doença de Alzheimer/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Albuminas/imunologia , Análise de Variância , Antígenos CD/sangue , Antígenos CD/líquido cefalorraquidiano , Antígenos CD/imunologia , Antígenos CD4/sangue , Antígenos CD4/líquido cefalorraquidiano , Antígenos CD4/imunologia , Feminino , Antígenos HLA-DR/sangue , Antígenos HLA-DR/líquido cefalorraquidiano , Antígenos HLA-DR/imunologia , Humanos , Imuno-Histoquímica , Interleucina-2/sangue , Interleucina-2/líquido cefalorraquidiano , Interleucina-2/imunologia , Masculino , Pessoa de Meia-Idade , Receptores de Interleucina-2/imunologia , Receptores de Interleucina-2/metabolismoRESUMO
Beta-nerve growth factor (beta-NGF) is a trophic factor in the nervous system. We aimed to isolate and characterize this protein in view of its potential therapeutic use in neurodegenerative diseases. For purification a two-step ion-exchange procedure was followed. The characterization was performed using separation and immunological techniques, as well as a biological assay. These studies showed that the obtained protein consisted of a mixture of beta-NGF molecules, intact at their NH2-terminal extreme, and molecules which have lost the NH2-terminal octapeptide and exhibit modifications increasing its hydrophobicity. All these molecular species were recognized immunologically and showed biological activity.