Evuloção cognitiva e funcional de pacientes pós-acidente vascular cerebral - AVC

PURPOSE: Stroke is a high-incidence cerebrovascular disease with elevated morbidity that results in impairments such as functional disabilities. This study aimed to investigate the functional evolution of individuals in the first six months post-stroke. METHOD: Longitudinal study with 42 stroke patients. The functional independence measure (FIM) and The National Institutes of Health Stroke Scale (NIHSS) were used by multidisciplinary staff 3 times in each participant; the first application was at admission to rehabilitation and the others three and six months later. RESULTS: Sample predominantly female (57%), married (52%), mean age 65.26 ±10.72 years, elementary schooling level (43%), ischemic stroke (91%), and right cerebral hemisphere (74%). Motor FIM scores and NIHSS scale showed improvement in the 3 evaluations, with significant p-value (<0.001). There was a strong relation between motor FIM evolution and NIHSS evolution (r = - 0.69 p-value< 0.001). CONCLUSIONS: It was observed that functional evolution at 6 months post-stroke was significant and the smaller the evolution of clinical impairment in these patients, the larger the evolution of their functional independence. The study is important because it allows a more appropriate therapeutic planning according with functional evolution in stroke rehabilitation

Seleção de categorias da Classificação Internacional de Funcionalidade, Incapacidade e Saúde para avaliação do paciente com acidente vascular cerebral em reabilitação

Stroke represents the first cause of disabilities among adults. Although different professions work together in treatment of stroke patients, all they use different terminologies for the description of the patients problems and it can constitute an impediment in the communication between the staff members. Thus, the multidisciplinary and interdisciplinary work would be facilitated if using a reference common tool, as the new International Classification of Functioning, Disability and Health (ICF). However, the ICF is very extensive and complex and due to its complexity, it has been evidenced the necessity to select its categories to become it more practical. The aim of the study was to investigate which categories of the ICF are more suitable to evaluate and to describe the stroke patient in the view of teachers and municipal public health professionals. It was a descriptive research, which involved 5 professors and 11 professionals of Physiotherapy that have worked at the health public area in Natal / RN. It was used the Delphi Technique in 3 rounds and the Likert Scale to select the categories among the ICF components. As result, from the 362 IFC categories, 94 were selected. The selected categories correspond to rehabilitative characteristics of Stroke patients in the universe of the Physiotherapy performance. The methodology applied was suitable to the studied object emphasizing the necessity of future studies for validation of the chosen categories

Avaliação neuropsicológica de crianças com hemiparesia congênita e adquirida

A hemiparesia consiste no déficit da força muscular, com consequente debilidade na mão e no pé, afetando um dos lados do corpo. A literatura mostra poucos estudos enfocando detalhadamente as funções cognitivas e emocionais de crianças afetadas por essa condição neurológica. Este estudo teve como objetivo realizar avaliação neuropsicológica de 23 crianças e adolescentes, de ambos os gêneros, com idades entre 5 anos e 4 meses e 16 anos e 6 meses, com hemiparesia congênita e adquirida. Aplicou-se uma bateria de testes específica para avaliação de funções cognitivas superiores incluindo processos intelectuais, atenção, função perceptiva, função motora, praxias, gnosias, linguagem, memória e função visuomotora. Em relação aos aspectos emocionais, foi usado o teste do desenho da figura humana, visando-se a avaliação da percepção da imagem corporal dos pacientes. Os resultados mostraram que a hemiparesia da criança conduz a déficits em funções neuropsicológicas importantes, além de déficit motor e alterações na esfera emocional, mais precisamente aquelas relacionadas com a representação da imagem corporal. A abrangência multidisciplinar, envolvendo a neurologia pediátrica e a psicologia, engrandeceu o trabalho, referendando os resultados obtidos em todos os seus aspectos

Physical-chemical analysis of the cerebrospinal fluid of healthy dogs submitted to different storage periods and temperatures

Disfunções envolvendo o sistema nervoso são de grande importância na Medicina Veterinária, pois tratam-se de enfermidades de elevada incidência e com poucos subsídios auxiliares no seu diagnóstico, prognóstico e na avaliação de terapias empregadas. Ainda hoje, o diagnóstico baseia-se, em grande parte, no histórico e no exame clínico neurológico. Dessa forma, a análise dos constituintes do fluido cefalorraquidiano torna-se uma das poucas alternativas de acesso clínico ao sistema nervoso central (SNC). Mesmo com a grande utilidade do exame físico-químico e citoscópico do liquor na neurologia veterinária, poucos são os estudos sobre a estabilidade dos seus constituintes sob estocagem. Dessa forma, o presente trabalho teve como finalidade verificar a influência da temperatura e do tempo de conservação nas características físico-químicas do liquor de cães hígidos. Para tanto, foram coletadas amostras de LCR, através da punção da cisterna cerebelo-medular de cães clinicamente sadios, as quais foram submetidas à análise da densidade específica, do pH, da glicorraquia, das proteínas totais e das atividades das enzimas creatina quinase (CK) e aspartato aminotransferase (AST), após conservá-las em diferentes temperaturas (25°C, 4°C e -4°C) e por diferentes períodos de tempo (logo após a colheita, 24 horas, 48 horas, uma semana e um mês). Dentre os resultados obtidos, foi possível verificar, principalmente, que houve estabilidade dos parâmetros estudados por até um mês de estocagem nas amostras mantidas sob a temperaturas de congelamento de -4°C.

Úlcera de pressão em pacientes internados em um hospital universitário em Natal/RN: condições predisponentes e fatores de risco

The pressure ulcers (PU), also known as decubitus ulcers, are defined as injuries caused by the constant pressure exerted on a particular point of the body, causing impairment of blood supply with a decrease or interruption of tissue irrigation, causing occlusion of blood vessels and capillaries, ischemia and cell death. This is a descriptive study with longitudinal design, and panel type, with quantitative approach that aimed to examine the association between predisposing conditions (PC), intrinsic factors (IF) and extrinsic factors (EF) with the occurrence of PU, in hospitalized patients in the Intensive Care Unit (ICU), pain clinical, surgical clinical and neurology wards of a university hospital. The study population was composed of all patients who were restricted to bed during the period from December 2007 to February 2008. The study was approved by the Ethics Committee of HUOL / UFRN (No 135/07). The data-collection took place through a structured formulary of observation, data from medical records and physical examination of patients skins. The results were organized in SPSS 15.0 software, tabulated, categorized and analyzed by descriptive and inferential statistics. Of the 30 patients studied, 43.3% had been hospitalized in the pain clinical and surgical clinic wards, 20.0% in the ICU, 20.0% in the ICU / ward and 16.7% in neurology, being the length of hospitalization in those units of 7 to 18 days (63.3%) and from 19 to 30 days (36.7%), predominantly female and aged ≥ 60 years (60.0%). 19 PU were diagnosed in 43.3% of patients monitored, being 38.5% with one PU between 7 to 18 days and 46.2% with two or more between 19 to 30 days of hospitalization, showing significant relationship (ρ-value = 0029) between length of hospital stay and the number of PU. Was found an association of 35.7% of the PC (cardio-respiratory, hematological, metabolic and psychogenic), IF (age group, oedema, skin changes in humidity and change of body temperature) and EF (type of mattress and strength of body pressure) for all patients studied, statistically significant (ρ-value = 0001), between the average scores in patients with and without PU, with reason chance to 12.0 for the development of PU and there was moderate correlation ( r = 0618) in the presence of this association. Results show the influence of the multiplicity of factors and conditions on the occurrence of PU, which brings us to reflect on the assistance focused on prevention and reduction of these injuries which will encourage the reduction of hospitalization length, physical and psychological suffering, and the possibility of improving the clinical condition of the patient.

Quantitative study of the myenteric plexus of the stomach of rats with streptozotocin-induced diabetes

A proposta deste trabalho foi estudar as alterações morfológicas e quantitativas dos neurônios do plexo mientérico do estômago de ratos com diabetes induzido por estreptozootocina e estabelecer uma comparação com animais não diabéticos. Amostras do corpo do estômago foram submetidas a preparados de membrana corados pelo método da NADH-diaforase e a cortes histológicos corados por hematoxilina-eosina. Observou-se que o diabetes provoca significante redução no número de neurônios.

A cafeína exerce efeitos positivos sobre a memória tipo episódica em ratos adultos sem influenciar a sobrevivência neural no giro dentado

The caffeine is a mild psychostimulant that has positive cognitive effects at low doses, while promotes detrimental effects on these processes at higher doses. The episodic-like memory can be evaluated in rodents through hippocampus-dependent tasks. The dentate gyrus is a hippocampal subregion in which neurogenesis occurs in adults, and it is believed that this process is related to the function of patterns separation, such as the identification of spatial and temporal patterns when discriminating events. Furthermore, neurogenesis is influenced spatial and contextual learning tasks. Our goal was to evaluate the performance of male Wistar rats in episodic-like tasks after acute or chronic caffeine treatment (15mg/kg or 30mg/kg). Moreover, we assessed the chronic effect of the caffeine treatment, as well as the influence of the hippocampus-dependent learning tasks, on the survival of new-born neurons at the beginning of treatment. For this purpose, we used BrdU to label the new cells generated in the dentate gyrus. Regarding the acute treatment, we found that the saline group presented a tendency to have better spatial and temporal discrimination than caffeine groups. The chronic caffeine group 15 mg/kg (low dose) showed the best discrimination of the temporal aspect of episodic-like memory, whereas the chronic caffeine group 30mg/kg (high dose) was able to discriminate temporal order, only in a condition of greater difficulty. Assessment of neurogenesis using immunohistochemistry for evaluating survival of new-born neurons generated in the dentate gyrus revealed no difference among groups of chronic treatment. Thus, the positive mnemonic effects of the chronic caffeine treatment were not related to neuronal survival. However, another plastic mechanism could explain the positive mnemonic effect, given that there was no improvement in the acute caffeine groups

Efeitos da eliminação de neurônios infragranulares sobre a especificação de neurônios supragranulares do córtex cerebral

The cerebral cortex of mammals is histologically organized into different layers of excitatory neurons that have distinct patterns of connections with cortical or subcortical targets. During development, these cortical layers are established through an intricate combination of neuronal specification and migration in a radial pattern known as "insideout": deep-layer neurons are generated prior to upper-layer neurons. In the last few decades, several genes encoding transcription factors involved in the sequential specification of neurons destined to different cortical layers have been identified. However, the influence of early-generated neurons in the specification of subsequent neuronal cohorts remains unclear. To investigate this possible influence, we induced the selective death of cortical neurons from layer V and VI before the generation of layer II, III and IV neurons. Thus, we can evaluate the effects of ablation of early born neurons on the phenotype of late born neurons. Our data shows that one-day after ablation, layer VI neurons expressing the transcription factor TBR1 are newly generated while virtually no neuron expressing TBR1 was generated in the same age in control animals. This suggests that progenitors involved in the generation of neurons destined for superficial layers suffer interference from the selective death of neurons in deep layers, changing their specification. We also observed that while TBR1-positive neurons are located exclusively in deep cortical layers of control animals, many TBR1-positive neurons are misplaced in superficial layers of ablated animals, suggesting that the migration of cortical neurons could be controlled independently of neuronal phenotypes. Furthermore, we observed an increase in layer V neurons expressing CTIP2 and neurons expressing SATB2 and that these cells have changed their distributions. As a conclusion, our data indicate the existence of a mechanism of control exercised by the early-generated neurons in the cerebral cortex on the fate of the progenitors involved in the generation of the following cortical neurons. This mechanism could help to control the number of neurons in different layers and contribute to the establishment of different cortical areas

Interferindo com oscilações de alta frequência no hipocampo epiléptico: consequências para as crises espontâneas

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Efeitos da sinalização via creb sobre a sobrevivência e diferenciação meuronal

The cortical development requires a precise process of proliferation, migration, survival and differentiation of newly formed neurons to finally achieve the development of a functional network. Different kinases, such as PKA, CaMKII, MAPK and PI3K, phosphorylate the transcription factors CREB, and thus activate it, inducing CREB-dependent gene expression. In order to identify the involvement of such signaling pathways mediated by CREB over neuronal differentiation and survival, in vitro experiments of cell culture were conducted using pharmacological kinase inhibitors and genetic techniques to express different forms of CREB (A-CREB and CREB-FY) in cortical neurons. Inhibition of PKA and CaMKII decreased the length of neuronal processes (neurites); whereas inhibition of MAPK did not affect the length, but increased the number of neurites. Blockade of PI3K do not appear to alter neuronal morphology, nor the soma size changed with the kinase blockades. CREB activation (CREB-FY) along with MAPK and PI3K blockades presented a negative side effect over neuritic growth and the expression of A-CREB leaded to a significant decrease in neuronal survival after 60h in vitro and mimicked some of the effects on neuronal morphology observed with PKA and CaMKII blockade. In summary the signaling through CREB influences the morphology of cortical neurons, particularly when phosphorylated by PKA, and CREB signaling is also important for survival of immature neurons prior to the establishment of fully functional synaptic contacts. Our data contribute to understanding the role of CREB signaling, activated by different routes, on survival and neuronal differentiation and may be valuable in the development of regenerative strategies in different neurological diseases

Encoding mechanisms based on fast oscillations in the retina of the cat and their dependencies on anesthesia

Processing in the visual system starts in the retina. Its complex network of cells with different properties enables for parallel encoding and transmission of visual information to the lateral geniculate nucleus (LGN) and to the cortex. In the retina, it has been shown that responses are often accompanied by fast synchronous oscillations (30 - 90 Hz) in a stimulus-dependent manner. Studies in the frog, rabbit, cat and monkey, have shown strong oscillatory responses to large stimuli which probably encode global stimulus properties, such as size and continuity (Neuenschwander and Singer, 1996; Ishikane et al., 2005). Moreover, simultaneous recordings from different levels in the visual system have demonstrated that the oscillatory patterning of retinal ganglion cell responses are transmitted to the cortex via the LGN (Castelo-Branco et al., 1998). Overall these results suggest that feedforward synchronous oscillations contribute to visual encoding. In the present study on the LGN of the anesthetized cat, we further investigate the role of retinal oscillations in visual processing by applying complex stimuli, such as natural visual scenes, light spots of varying size and contrast, and flickering checkerboards. This is a necessary step for understanding encoding mechanisms in more naturalistic conditions, as currently most data on retinal oscillations have been limited to simple, flashed and stationary stimuli. Correlation analysis of spiking responses confirmed previous results showing that oscillatory responses in the retina (observed here from the LGN responses) largely depend on the size and stationarity of the stimulus. For natural scenes (gray-level and binary movies) oscillations appeared only for brief moments probably when receptive fields were dominated by large continuous, flat-contrast surfaces. Moreover, oscillatory responses to a circle stimulus could be broken with an annular mask indicating that synchronization arises from relatively local interactions among populations of activated cells in the retina. A surprising finding in this study was that retinal oscillations are highly dependent on halothane anesthesia levels. In the absence of halothane, oscillatory activity vanished independent of the characteristics of the stimuli. The same results were obtained for isoflurane, which has similar pharmacological properties. These new and unexpected findings question whether feedfoward oscillations in the early visual system are simply due to an imbalance between excitation and inhibition in the retinal networks generated by the halogenated anesthetics. Further studies in awake behaving animals are necessary to extend these conclusions

Caracterização comportamental e distribuição de neurônios inibitórios em um modelo animal de autismo induzido por ácido valpróico

Autism comprises a heterogeneous group of neurodevelopmental disorders that affects the brain maturation and produces sensorial, motor, language and social interaction deficits in early childhood. Several studies have shown a major involvement of genetic factors leading to a predisposition to autism, which are possibly affected by environmental modulators during embryonic and post-natal life. Recent studies in animal models indicate that alterations in epigenetic control during development can generate neuronal maturation disturbances and produce a hyper-excitable circuit, resulting in typical symptoms of autism. In the animal model of autism induced by valproic acid (VPA) during rat pregnancy, behavioral, electrophysiological and cellular alterations have been reported which can also be observed in patients with autism. However, only a few studies have correlated behavioral alterations with the supposed neuronal hyper-excitability in this model. The aim of this project was to generate an animal model of autism by pre-natal exposure to VPA and evaluate the early post-natal development and pre-puberal (PND30) behavior in the offspring. Furthermore, we quantified the parvalbumin-positive neuronal distribution in the medial prefrontal cortex and Purkinje cells in the cerebellum of VPA animals. Our results show that VPA treatment induced developmental alterations, which were observed in behavioral changes as compared to vehicle-treated controls. VPA animals showed clear behavioral abnormalities such as hyperlocomotion, prolonged stereotipies and reduced social interaction with an unfamiliar mate. Cellular quantification revealed a decrease in the number of parvalbumin-positive interneurons in the anterior cingulate cortex and in the prelimbic cortex of the mPFC, suggesting an excitatory/inhibitory unbalance in this animal model of autism. Moreover, we also observed that the neuronal reduction occurred mainly in the cortical layers II/III and V/VI. We did not detect any change in the density of Purkinje neurons in the Crus I region of the cerebellar cortex. Together, our results strengthens the face validity of the VPA model in rats and shed light on specific changes in the inhibitory circuitry of the prefrontal cortex in this autism model. Further studies should address the challenges to clarify particular electrophysiological correlates of the cellular alterations in order to better understand the behavioral dysfunctions

Revisitando o eletrocorticograma intra-operatório na epilepsia mesial do lobo temporal: relevância das oscilações de alta frequência

Epilepsies are neurological disorders characterized by recurrent and spontaneous seizures due to an abnormal electric activity in a brain network. The mesial temporal lobe epilepsy (MTLE) is the most prevalent type of epilepsy in adulthood, and it occurs frequently in association with hippocampal sclerosis. Unfortunately, not all patients benefit from pharmacological treatment (drug-resistant patients), and therefore become candidates for surgery, a procedure of high complexity and cost. Nowadays, the most common surgery is the anterior temporal lobectomy with selective amygdalohippocampectomy, a procedure standardized by anatomical markers. However, part of patients still present seizure after the procedure. Then, to increase the efficiency of this kind of procedure, it is fundamental to know the epileptic human brain in order to create new tools for auxiliary an individualized surgery procedure. The aim of this work was to identify and quantify the occurrence of epilepticform activity -such as interictal spikes (IS) and high frequency oscillations (HFO) - in electrocorticographic (ECoG) signals acutely recorded during the surgery procedure in drug-resistant patients with MTLE. The ECoG recording (32 channels at sample rate of 1 kHz) was performed in the surface of temporal lobe in three moments: without any cortical resection, after anterior temporal lobectomy and after amygdalohippocampectomy (mean duration of each record: 10 min; N = 17 patients; ethic approval #1038/03 in Research Ethic Committee of Federal University of São Paulo). The occurrence of IS and HFO was quantified automatically by MATLAB routines and validated manually. The events rate (number of events/channels) in each recording time was correlated with seizure control outcome. In 8 hours and 40 minutes of record, we identified 36,858 IS and 1.756 HFO. We observed that seizure-free outcome patients had more HFO rate before the resection than non-seizure free, however do not differentiate in relation of frequency, morphology and distribution of IS. The HFO rate in the first record was better than IS rate on prediction of seizure-free patients (IS: AUC = 57%, Sens = 70%, Spec = 71% vs HFO: AUC = 77%, Sens = 100%, Spec = 70%). We observed the same for the difference of the rate of pre and post-resection (IS: AUC = 54%, Sens = 60%, Spec = 71%; vs HFO: AUC = 84%, Sens = 100%, Spec = 80%). In this case, the algorithm identifies all seizure-free patients (N = 7) with two false positives. To conclude, we observed that the IS and HFO can be found in intra-operative ECoG record, despite the anesthesia and the short time of record. The possibility to classify the patients before any cortical resection suggest that ECoG can be important to decide the use of adjuvant pharmacological treatment or to change for tailored resection procedure. The mechanism responsible for this effect is still unknown, thus more studies are necessary to clarify the processes related to it

Efeitos da administração aguda de quetamina sobre as oscilações eletrofisiológicas da região CA1 hipocampal

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

The influence of visual inter-hemispheric connections on spiking, assembly and LFP activities, and their phase relationship during figure-ground stimulation

Desde os descobrimentos pioneiros de Hubel e Wiesel acumulou-se uma vasta literatura descrevendo as respostas neuronais do córtex visual primário (V1) a diferentes estímulos visuais. Estes estímulos consistem principalmente em barras em movimento, pontos ou grades, que são úteis para explorar as respostas dentro do campo receptivo clássico (CRF do inglês classical receptive field) a características básicas dos estímulos visuais como a orientação, direção de movimento, contraste, entre outras. Entretanto, nas últimas duas décadas, tornou-se cada vez mais evidente que a atividade de neurônios em V1 pode ser modulada por estímulos fora do CRF. Desta forma, áreas visuais primárias poderiam estar envolvidas em funções visuais mais complexas como, por exemplo, a separação de um objeto ou figura do seu fundo (segregação figura-fundo) e assume-se que as conexões intrínsecas de longo alcance em V1, assim como as conexões de áreas visuais superiores, estão ativamente envolvidas neste processo. Sua possível função foi inferida a partir da análise das variações das respostas induzidas por um estímulo localizado fora do CRF de neurônios individuais. Mesmo sendo muito provável que estas conexões tenham também um impacto tanto na atividade conjunta de neurônios envolvidos no processamento da figura quanto no potencial de campo, estas questões permanecem pouco estudadas. Visando examinar a modulação do contexto visual nessas atividades, coletamos potenciais de ação e potenciais de campo em paralelo de até 48 eletrodos implantados na área visual primária de gatos anestesiados. Estimulamos com grades compostas e cenas naturais, focando-nos na atividade de neurônios cujo CRF estava situado na figura. Da mesma forma, visando examinar a influência das conexões laterais, o sinal proveniente da área visual isotópica e contralateral foi removido através da desativação reversível por resfriamento. Fizemos isso devido a: i) as conexões laterais intrínsecas não podem ser facilmente manipuladas sem afetar diretamente os sinais que estão sendo medidos, ii) as conexões inter-hemisféricas compartilham as principais características anatômicas com a rede lateral intrínseca e podem ser vistas como uma continuação funcional das mesmas entre os dois hemisférios e iii) o resfriamento desativa as conexões de forma causal e reversível, silenciando temporariamente seu sinal, permitindo conclusões diretas a respeito da sua contribuição. Nossos resultados demonstram que o mecanismo de segmentação figurafundo se reflete nas taxas de disparo de neurônios individuais, assim como na potência do potencial de campo e na relação entre sua fase e os padrões de disparo produzidos pela população. Além disso, as conexões laterais inter-hemisféricas modulam estas variáveis dependendo da estimulação feita fora do CRF. Observamos também uma influência deste circuito lateral na coerência entre potenciais de campo entre eletrodos distantes. Em conclusão, nossos resultados dão suporte à ideia de um mecanismo complexo de segmentação figura-fundo atuando desde as áreas visuais primárias em diferentes escalas de frequência. Esse mecanismo parece envolver grupos de neurônios ativos sincronicamente e dependentes da fase do potencial de campo. Nossos resultados também são compatíveis com a hipótese que conexões laterais de longo alcance também fazem parte deste mecanismo