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• W2208481514 startingPage "151" @default.
• W2208481514 abstract "The central nervous system white matter is damaged during an ischemic stroke and therapeutic strategies derived from experimental studies focused exclusively on young adults and gray matter have been unsuccessful in the more clinically relevant aging population. The risk for stroke increases with age and the white matter inherently becomes more susceptible to injury as a function of age. Age-related changes in the molecular architecture of white matter determine the principal injury mechanisms and the functional outcome. A prominent increase in the main plasma membrane Na(+)-dependent glutamate transporter, GLT-1/EAAT2, together with increased extracellular glutamate levels may reflect an increased need for glutamate signaling in the aging white matter to maintain its function. Mitochondria exhibit intricate dynamics to efficiently buffer Ca(2+), to produce sufficient ATP, and to effectively scavenge reactive oxygen species (ROS) in response to excitotoxicity to sustain axon function. Aging exacerbates mitochondrial fusion, leading to progressive alterations in mitochondrial dynamics and function, presumably to effectively buffer increased Ca(2+) load and ROS production. Interestingly, these adaptive adjustments become detrimental under ischemic conditions, leading to increased and early glutamate release and a rapid exhaustion of mitochondrial capacity to sustain energy status of axons. Consequently, protective interventions in young white matter become injurious or ineffective to promote recovery in aging white matter after an ischemic episode. An age-specific understanding of the mechanisms of injury processes in white matter is vital in order to design dynamic therapeutic approaches for stroke victims." @default.
• W2208481514 created "2016-06-24" @default.
• W2208481514 creator A5084871376 @default.
• W2208481514 date "2014-01-01" @default.
• W2208481514 modified "2023-09-27" @default.
• W2208481514 title "Excitotoxicity and Mitochondrial Dysfunction Underlie Age-Dependent Ischemic White Matter Injury" @default.
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• W2208481514 doi "https://doi.org/10.1007/978-3-319-08894-5_8" @default.
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