RESUMO
Seizure-driven brain damage in epilepsy accumulates over time, especially in the hippocampus, which can lead to sclerosis, cognitive decline, and death. Excitotoxicity is the prevalent model to explain ictal neurodegeneration. Current labeling technologies cannot distinguish between excitotoxicity and hypoxia, however, because they share common molecular mechanisms. This leaves open the possibility that undetected ischemic hypoxia, due to ictal blood flow restriction, could contribute to neurodegeneration previously ascribed to excitotoxicity. We tested this possibility with Confocal Laser Endomicroscopy (CLE) and novel stereological analyses in several models of epileptic mice. We found a higher number and magnitude of NG2+ mural-cell mediated capillary constrictions in the hippocampus of epileptic mice than in that of normal mice, in addition to spatial coupling between capillary constrictions and oxidative stressed neurons and neurodegeneration. These results reveal a role for hypoxia driven by capillary blood flow restriction in ictal neurodegeneration.
Assuntos
Capilares/patologia , Epilepsia/patologia , Hipocampo/patologia , Hipóxia/patologia , Doenças Neurodegenerativas/patologia , Convulsões/patologia , Animais , Antígenos/genética , Antígenos/metabolismo , Velocidade do Fluxo Sanguíneo , Capilares/diagnóstico por imagem , Capilares/metabolismo , Circulação Cerebrovascular , Modelos Animais de Doenças , Epilepsia/diagnóstico por imagem , Epilepsia/metabolismo , Expressão Gênica , Hipocampo/irrigação sanguínea , Hipocampo/diagnóstico por imagem , Hipocampo/metabolismo , Humanos , Hipóxia/diagnóstico por imagem , Hipóxia/metabolismo , Camundongos , Microscopia Confocal , Doenças Neurodegenerativas/diagnóstico por imagem , Doenças Neurodegenerativas/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Estresse Oxidativo , Proteoglicanas/genética , Proteoglicanas/metabolismo , Convulsões/diagnóstico por imagem , Convulsões/metabolismoRESUMO
Injury to pedestrians is a major safety hazard in many countries. Since the beginning of the last century, modern cities have been designed around the use of motor vehicles despite the unfavourable interactions between the vehicles and pedestrians. This push towards urbanization resulted in a substantial number of crashes and fatalities involving pedestrians every day, all over the world. Thus, improving the design of urban cities and townships is a pressing issue for modern society. The study presented here provides a characterization of pedestrian safety problems, with the emphasis on signalized crosswalks (i.e. traffic signal) design solutions. We tested the impact of seven different traffic light configurations (steady [green, yellow, and red], flashing [green, yellow, and red], and light off) on pedestrian self-reported road-crossing behavior, using a 11-point scale -ranging from 0 («I never cross in this situation») to 10 («I always cross in this situation»). Results showed that mandatory solutions (steady green vs. steady red) are the best solutions to avoid unsafe pedestrian behaviors while crossing controlled intersections (frequency of crossing: Mgreen = 9.4 ± 1 vs. Mred = 2.6 ± 2). These findings offer important guidelines for the design of future traffic signals for encouraging a pedestrian/transit-friendly environment (AU)
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