RESUMO
BACKGROUND: ß-amyloid (Aß) can accumulate in the brain of aged dogs, and within vessels walls, the disease is called cerebral amyloid angiopathy (CAA). In humans, Alzheimer's disease and CAA are strongly correlated with cerebrovascular disease. However, in dogs, this association has not been extensively studied yet. The present report highlights the pathological and clinical features of a concomitant cerebrovascular disease and amyloid precursor protein (APP) accumulation in the brain of a dog. CASE PRESENTATION: A female, 16-year-old, Standard Poodle with a one-year history of cognitive deficits presented with an acute onset of right-sided postural reaction deficit and circling, left-sided head tilt, positional nystagmus, and ataxia. Due to poor prognosis the dog was euthanized, and pathological examination of the brain revealed an acute lacunar infarction within the thalamus extending to rostral colliculus. Additional findings included subacute and chronic areas of ischemia throughout the brain and areas of hemorrhage within the medulla. Immunolabeling revealed APP deposition within intraparenchymal vessels of frontal, temporal and occipital cortex, hippocampus, diencephalon, mesencephalon and myelencephalon, besides meningeal vessels walls. Glial fibrillary acidic protein (GFAP) immunolabeling showed marked astrocytosis around the acute area of infarction and within chronic areas of ischemia. Histological examination of the brain along with immunohistochemistry results showed a concomitant APP, which is an Aß precursor, accumulation within the neuroparenchyma and vessels (CAA) with histological evidences of a cerebrovascular disease in an aged dog. CONCLUSIONS: This report shows that APP accumulation in the brain can occur concomitantly to a severe cerebrovascular disease in a dog. Further studies are necessary to elucidate if cerebrovascular disease is associated with Aß accumulation in the brain of dogs.
Assuntos
Precursor de Proteína beta-Amiloide/metabolismo , Infarto Encefálico/veterinária , Encéfalo/metabolismo , Angiopatia Amiloide Cerebral/veterinária , Doenças do Cão/fisiopatologia , Animais , Infarto Encefálico/etiologia , Infarto Encefálico/metabolismo , Angiopatia Amiloide Cerebral/metabolismo , Angiopatia Amiloide Cerebral/fisiopatologia , Doenças do Cão/metabolismo , Cães , FemininoRESUMO
The p75 neurotrophin receptor (p75(NTR)) is involved in neuronal functions ranging from induction of apoptosis and growth inhibition to the promotion of survival. p75(NTR) expression is induced in the central nervous system (CNS) by a range of pathological conditions, where it seems to have a role in neuronal death and axonal growth inhibition. The cellular mechanisms driving p75(NTR) expression in cell lines and primary neurons is Sp1 dependent (Ramos et al. [2007] J. Neurosci. 27:1498). In this study, we analyzed the spatiotemporal profile of p75(NTR) expression after an ischemic lesion induced by cortical devascularization (CD). Our results show that p75(NTR) expression occurs in isolated neurons of the ischemic lesion site. The p75(NTR+) neurons presented morphological alterations and active caspase-3 staining. Some p75(NTR+) neurons were also positive for sortilin. The peak of p75(NTR) expression was localized 3 days postlesion (3DPL) in the penumbra. Sp1 transcription factor nuclear localization was observed in p75(NTR+) neurons. The overall level of Sp1 expression was increased until 14DPL on the ipsilateral hemisphere. With primary cortical neurons, we demonstrated that p75(NTR) expression is induced by excitotoxic stress and correlated with increased Sp1 abundance. We conclude that p75(NTR) expression is localized in selected neurons of the ischemic lesion and that these neurons are probably condemned to apoptotic cell death. In primary neuronal culture, it is clear that excitotoxicity and Sp1 are involved in induction of p75(NTR) expression, although, in vivo, some additional mechanisms are likely to be involved in the control of p75(NTR) expression in specific neurons in vivo.
Assuntos
Isquemia Encefálica/metabolismo , Córtex Cerebral/metabolismo , Transtornos Cerebrovasculares/metabolismo , Neurônios/metabolismo , Receptores de Fator de Crescimento Neural/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Animais , Apoptose/fisiologia , Infarto Encefálico/metabolismo , Infarto Encefálico/patologia , Infarto Encefálico/fisiopatologia , Isquemia Encefálica/patologia , Isquemia Encefálica/fisiopatologia , Caspase 3/metabolismo , Células Cultivadas , Artérias Cerebrais/patologia , Artérias Cerebrais/fisiopatologia , Artérias Cerebrais/cirurgia , Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/fisiopatologia , Transtornos Cerebrovasculares/patologia , Transtornos Cerebrovasculares/fisiopatologia , Modelos Animais de Doenças , Masculino , Degeneração Neural/metabolismo , Degeneração Neural/patologia , Degeneração Neural/fisiopatologia , Proteínas do Tecido Nervoso , Neurônios/patologia , Neurotoxinas/metabolismo , Ratos , Ratos Wistar , Receptores de Fatores de Crescimento , Fator de Transcrição Sp1/metabolismo , Estresse Fisiológico/fisiologia , Regulação para Cima/fisiologiaRESUMO
Stroke syndromes are a major cause of disability in middle and later life resulting in severe neuronal degeneration and loss of brain functions. In situations with energy failure, glutamate transport is impaired and high levels of this amino acid accumulate on the synaptic cleft. Our group has showed that guanosine exerts neuroprotection against neurotoxicity situations. The aim of this work is draw a post-ischemic profile of glutamate uptake and cell damage using an oxygen and glucose deprivation model (OGD) in hippocampal slices from young (P10) and adult (P60) rats, analyzing guanosine effect. OGD decreases glutamate uptake in both ages and recovery times, although decrease in cell viability was only observed 1 and 3 h after OGD in young and adult animals, respectively. Guanosine partially protected cell damage from 1 h in P10 and at 3 h in P60 rats and avoided glutamate uptake decrease from P10 rats at 3 h. The impairment of glutamate transporters since immediately after the insult observed here is probably due to an energetic failure; loss of cell viability was only observed from 1 h after OGD. The mechanism by which guanosine acts in the 'ischemic' model used here is still unknown, but evidence leads to its antiapoptotic effect.
Assuntos
Envelhecimento/metabolismo , Ácido Glutâmico/metabolismo , Guanosina/metabolismo , Hipocampo/crescimento & desenvolvimento , Hipocampo/metabolismo , Hipóxia-Isquemia Encefálica/metabolismo , Sistema X-AG de Transporte de Aminoácidos/efeitos dos fármacos , Sistema X-AG de Transporte de Aminoácidos/metabolismo , Animais , Animais Recém-Nascidos , Transporte Biológico Ativo/efeitos dos fármacos , Transporte Biológico Ativo/fisiologia , Infarto Encefálico/tratamento farmacológico , Infarto Encefálico/metabolismo , Infarto Encefálico/fisiopatologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/fisiologia , Guanosina/farmacologia , Hipocampo/fisiopatologia , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Hipóxia-Isquemia Encefálica/fisiopatologia , Masculino , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/metabolismo , Fármacos Neuroprotetores/farmacologia , Técnicas de Cultura de Órgãos , Ratos , Ratos WistarRESUMO
We have recently demonstrated that high intensity training exercise exacerbates brain damage, while a moderate intensity (2 weeks of 20 min/day of treadmill training) reduces the injury caused by in vitro ischemia, oxygen and glucose deprivation (OGD), to hippocampal slices from Wistar rats. In the present paper, the effect of different running programs on severity of ischemic OGD lesion was examined, by the evaluation of three protocols designed to simulate exercise conditions common to humans: one or three 20-min sessions per week, during 12 weeks (moderate intensity), and two 20-min daily sessions for 3 weeks. OGD caused an increase of lactate dehydrogenase (LDH) release into the incubation media, a marker of tissue necrosis, and a decline of cell viability, as assessed by the decrease of mitochondrial dehydrogenase activity (MTT method). Moderate exercise, three times a week during 12-week treadmill training, decreased LDH release after OGD, while one weekly session and 3 weeks of two daily sessions did not affect OGD-induced LDH released. No exercise protocol evaluated altered MTT reduction. Our data support the hypothesis that moderate intensity exercise reduces hippocampal susceptibility to in vitro ischemia.