RESUMO
Stroke is a leading cause of death and a major contributor to neurological disability in adults. Tissue plasminogen activator is the only approved treatment. However, due to its narrow therapeutic window, <5% of patients receive treatment. Recently, hypoxic postconditioning (HPC) was shown to reduce stroke induced-injury in mice, but the mechanisms and functional outcomes are still unknown. In the current study, male Sprague Dawley rats were subjected to endothelin-1 induced stroke. HPC (8% O2, 1â¯h/d for 5d) or normoxia treatments were started 24â¯h after stroke. Behavioural tests were performed at various time-points (pre- and post-surgery, 1 and 6â¯days post stroke) and brains were collected 6â¯days after stroke for histological and immunoblotting analysis. HPC improved deficits in neurological score, motor and sensory function after stroke. Furthermore, HPC reduced infarct volume and neuronal loss in the cortex, while it increased the number of astrocytes and of Fluoro-Jade-positive cells in the injured hemisphere. We observed a mild increase in HIF-1 and its target gene, glucose transporter-1. Our data suggest that HPC-induced neuroprotection was mediated by enhanced astrocyte function, which may have contributed to functional recovery after stroke.
Assuntos
Endotelina-1 , Hipóxia/patologia , Infarto da Artéria Cerebral Média/induzido quimicamente , Infarto da Artéria Cerebral Média/patologia , Animais , Astrócitos/patologia , Comportamento Animal , Transportador de Glucose Tipo 1/genética , Elevação dos Membros Posteriores , Hipóxia/psicologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Infarto da Artéria Cerebral Média/psicologia , Masculino , Neurônios/patologia , Neuroproteção , Desempenho Psicomotor , Ratos , Ratos Sprague-Dawley , Reconhecimento Psicológico , Acidente Vascular Cerebral/fisiopatologiaRESUMO
OPINION STATEMENT: Metastatic colorectal cancer (CRC) is the second leading cause of cancer related mortality in the United States. The median age of patients at diagnosis is over 70, so as the American population ages, it can be expected that the incidence of CRC will also increase. There is limited prospective data regarding the safety and efficacy of chemotherapy in elderly patients with metastatic CRC. However, the data that are available suggest that elderly patients with a good performance status have a similar likelihood of response to currently available chemotherapy, though perhaps a somewhat higher likelihood of toxicities such as myelosuppression. This paper reviews the available data and recommendations for the treatment of this patient population.