RESUMO
BACKGROUND: Erythropoietin (EPO) upregulates the mitogen activated protein kinase (MAPK) cascade, a central signaling pathway in cellular plastic mechanisms, and is critical for normal brain development. OBJECTIVE: We hypothesized that EPO could modulate the plasticity mechanisms supporting spatial memory recovery in fimbria-fornix-transected animals. METHODS: Fimbria-fornix was transected in 3 groups of rats. Seven days later, EPO was injected daily for 4 consecutive days within 10 minutes after training on a water maze task. RESULTS: Our results show that EPO injections 10 minutes after training produced a substantial spatial memory recovery in fimbria-fornix-lesioned animals. In contrast, an EPO injection shortly after fimbria-fornix lesion surgery does not promote spatial-memory recovery. Neither does daily EPO injection 5 hours after the water maze performance. EPO, on the other hand, induced the expression of plasticity-related genes like arc and bdnf, but this effect was independent of training or lesion. CONCLUSIONS: This finding supports our working hypothesis that EPO can modulate transient neuroplastic mechanisms triggered by training in lesioned animals. Consequently, we propose that EPO administration can be a useful trophic factor to promote neural restoration when given in combination with training.
Assuntos
Eritropoetina/uso terapêutico , Fórnice/lesões , Transtornos da Memória/tratamento farmacológico , Plasticidade Neuronal/efeitos dos fármacos , Recuperação de Função Fisiológica/efeitos dos fármacos , Análise de Variância , Animais , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Lesões Encefálicas/complicações , Lesões Encefálicas/patologia , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Modelos Animais de Doenças , Fórnice/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hemoglobinas/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/etiologia , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Ratos , Ratos Wistar , Fatores de TempoRESUMO
OBJECTIVE: To evaluate white matter (WM) integrity of distinct groups of patients with antiepileptic drug (AED)-resistant localization-related epilepsies. METHODS: We used diffusion tensor imaging (DTI) fiber-tractography and voxel-based morphometry (VBM) to investigate differences of WM micro- and macrostructural integrity in patients with different drug-resistant localization-related epilepsies: 17 with temporal lobe epilepsy with magnetic resonance imaging (MRI) signs of hippocampal sclerosis (TLE-HS), 17 with TLE and normal MRI (TLE-NL), 14 with frontal lobe epilepsy and subtle MRI signs of focal cortical dysplasia (FLE-FCD), and 112 healthy controls. We performed fiber-tractography using a semiautomatic deterministic method to yield average fractional anisotropy (FA), axial (AD), and radial (RD) diffusivity ipsilateral and contralateral to the epileptogenic zone of the following tracts based on their functional and anatomic relevance: body of fornix (BoF), body of cingulum (BoC), inferior frontal occipital (IFO), and uncinate fasciculi (UF). In addition, we performed VBM of the WM maps to assess macrostructural integrity differences among groups. RESULTS: TLE-HS had ipsilateral and contralateral decreased FA and increased RD for all tracts. VBM showed WM alterations mainly in the ipsilateral parahippocampal region and contralateral superior temporal gyrus. FLE-FCD showed bilateral FA decreases only in the BoC and ipsilateral RD increases also in the BoC. VBM showed WM reduction mainly in the ipsilateral precuneus and posterior and anterior cingulum. No significant WM alterations were found in the TLE-NL in DTI or VBM analysis. SIGNIFICANCE: WM abnormalities differ in distinct AED-resistant localization-related epilepsies. The diverse distribution of the WM damage in these patients suggests that the localization of the epileptic networks may play a role in the WM burden. However, the distinct degree of this damage, more accentuated in TLE-HS, also suggests that the underlying cause of the epilepsy is probably an additional factor to explain this WM damage.
Assuntos
Epilepsia do Lobo Frontal/patologia , Epilepsia do Lobo Temporal/patologia , Hipocampo/patologia , Malformações do Desenvolvimento Cortical/patologia , Substância Branca/patologia , Adulto , Anticonvulsivantes/uso terapêutico , Encéfalo/patologia , Estudos de Casos e Controles , Imagem de Tensor de Difusão , Resistência a Medicamentos , Epilepsia do Lobo Frontal/complicações , Epilepsia do Lobo Frontal/tratamento farmacológico , Epilepsia do Lobo Temporal/tratamento farmacológico , Feminino , Fórnice/patologia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Malformações do Desenvolvimento Cortical/complicações , Pessoa de Meia-Idade , Tamanho do Órgão , Esclerose , Adulto JovemAssuntos
Transtornos do Sistema Nervoso Induzidos por Álcool/patologia , Alcoolismo/complicações , Núcleos Anteriores do Tálamo/patologia , Hemorragia Cerebral/patologia , Fórnice/patologia , Síndrome de Korsakoff/patologia , Transtornos do Sistema Nervoso Induzidos por Álcool/diagnóstico , Núcleos Anteriores do Tálamo/irrigação sanguínea , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/etiologia , Fórnice/irrigação sanguínea , Humanos , Síndrome de Korsakoff/diagnóstico , Síndrome de Korsakoff/etiologia , Masculino , Pessoa de Meia-Idade , Deficiência de Tiamina/etiologia , Deficiência de Tiamina/terapiaRESUMO
INTRODUCTION: Sperry, or interhemispheric disconnection, syndrome was reported in patients who had undergone surgical section of the corpus callosum carried out in an attempt to control medication-resistant epilepsy. It has occasionally been linked to tumours of the corpus callosum and, although even more rarely, it has also been associated to an amnesic syndrome. In this paper we report the anatomical and neuropsychological findings in a patient with interhemispheric disconnection syndrome associated to a hippocampal-type amnesic syndrome, caused by a tumour in the splenius of the corpus callosum that extended into the fornix. CASE REPORT: A 52-year-old white male who visited because of loss of memory; on admission to hospital the physical examination revealed a certain degree of asomatognosia with regard to the left-hand side of the body. An axial tomography brain scan showed a dense central lesion in the brain that extended laterally and occluded the body of both lateral ventricles. A biopsy study revealed an undifferentiated astrocytoma that affected the corpus callosum and the fornix. CONCLUSIONS: Sperry, or interhemispheric disconnection, syndrome produced by a tumour in the splenius of the corpus callosum is very likely to course with an amnesic syndrome due to disconnection caused by destruction of the fornix. This association, which characterised our patient's clinical picture, has only previously been described in three cases.
Assuntos
Amnésia Anterógrada , Astrocitoma/patologia , Neoplasias Encefálicas/patologia , Córtex Cerebral/patologia , Corpo Caloso/patologia , Fórnice/patologia , Amnésia Anterógrada/etiologia , Amnésia Anterógrada/fisiopatologia , Astrocitoma/complicações , Neoplasias Encefálicas/complicações , Córtex Cerebral/anatomia & histologia , Corpo Caloso/anatomia & histologia , Corpo Caloso/fisiologia , Evolução Fatal , Lateralidade Funcional , Humanos , Masculino , Pessoa de Meia-Idade , Vias Neurais/fisiologia , Testes Neuropsicológicos , SíndromeRESUMO
PURPOSE: Analysis of the parahippocampal gyrus (PHG) involvement in 115 patients with hippocampal sclerosis (HS) by MR imaging. The simultaneous occurrence of ipsilateral fornix (F) and mamillary body (MB) volume loss was checked also. These findings were correlated with the side of hippocampal involvement, the sex, patient s age, and the symptoms onset. METHOD: The MR images of 115 patients with HS were studied retrospectively. All the examinations were performed on 1.5 T units (SIGNA, GE, Milwaukee, WI) and included high resolution coronal T2-weighted images (3 mm thickness, 0.6 mm gap). RESULTS: The patient's age ranged between 3.5 and 80 years (mean 34.1); 62 (53.9%) were female and 53 (46.1%) were male. There were HS on the left side in 53 (46.0%), on the right side in 51 (44.3%), and bilateral in 11 (9.7%). In 43 (37.3%) cases there were ipsilateral PHG volume loss and signal hyper intensity on T2-weighted imaging. In 29 (25.2%) cases there were ipsilateral fornix volume loss and in 10 (34.5%) of this there were also ipsilateral MB changes. In abnormal PHG, 23 (53.4%) were on the left side, 17 (39.5%) were on the right side, and 3 (7.1%) were bilateral. There were fornix changes in 15 (34.8%) cases and MB volume loss in 5 (11.6%) cases. Pertinent clinical data were obtained in only 18 (41.8%) of the PHG lesion cases and 11 (61.1%) of these patients had epileptic attacks for more than 20 years before the examination. CONCLUSION: PHG involvement must be investigated in patients with HS and we suggest that the term mesial temporal sclerosis should be used only if there are also changes at this anatomical site.
Assuntos
Epilepsia do Lobo Temporal/patologia , Hipocampo/patologia , Giro Para-Hipocampal/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Atrofia , Criança , Pré-Escolar , Epilepsia do Lobo Temporal/complicações , Epilepsia do Lobo Temporal/cirurgia , Feminino , Fórnice/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Corpos Mamilares/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Esclerose/complicações , Esclerose/patologiaRESUMO
INTRODUCTION: Numerous reports show that lesions to hippocampus afferents, such as the entorhinal cortex (EC) and the fimbria fornix (FF), exert an effect on memory in rodents. There are, however, no long term comparative studies that show which of these lesions could be most useful as a model for studies into neuroplasticity. MATERIAL AND METHODS: Young male Sprague Dawley rats were used. Bilateral electrolytic lesion was caused to the EC or the FF was damaged by transection. One, four or 12 weeks later the animals were evaluated in a Morris water maze, first with an invisible platform and then with the platform within view. The results from the two groups were compared to each other and to those obtained from healthy controls and subjects with false lesions by means of a variance analysis. RESULTS: In the test with an invisible platform, both types of lesion gave rise to serious, irreparable involvement of the spatial memory of the animals, at least up to 12 weeks after the lesion. The test with the visible platform revealed significant differences between animals with lesion to the EC evaluated at 12 weeks, which suggests the development of some visual or motor deterioration in these animals. CONCLUSIONS: Although both lesions gave rise to behavioural deterioration that was irreversible in the long term in rodents, the lesion to the FF seems to be a better model for evaluating specific effects on learning and memory, since the lesion to the EC apparently triggers additional sensory and motor involvement.
Assuntos
Encefalopatias/patologia , Córtex Entorrinal/patologia , Fórnice/patologia , Memória/fisiologia , Animais , Encefalopatias/fisiopatologia , Humanos , Masculino , Aprendizagem em Labirinto , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
INTRODUCTION: Lesion of the fimbria-fornix causes dysfunction of learning processes and has been used in animal models for the study of Alzheimer's disease. MATERIAL AND METHODS: With the objective of comparing the efficacy of two methods of producing a lesion of the fimbria-fornix, 40 young male Sprague-Dawley rats were distributed in four experimental groups: control (6), falsely lesioned (8), lesion due to aspiration (12) and lesion due to transection (14). RESULTS: The results showed that whilst with both techniques, in rats, serious cognitive defects were produced, as expressed by the high latencies of escape and small number of crossings of Morris's aquatic labyrinth, the aspiration lesion led to greater mortality than the transection lesion did. Similarly, the aspiration technique in rats induced hyperactivity, aggressiveness and tigmotaxia, while in the rats with lesions due to transection tigmotaxia ceased after their first attempts and hyperactivity on the second day of training. CONCLUSION: These results would suggest that a bilateral lesion due to transection of the fimbria-fornix is an effective alternative to an aspiration lesion to interrupt this pathway.