Age-dependent exacerbation of white matter stroke outcomes: a role for oxidative damage and inflammatory mediators.
Age-dependent exacerbation of white matter stroke outcomes: a role for oxidative damage and inflammatory mediators.
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DOI：
10.1161/strokeaha.113.001796
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发表时间：
2013-09
期刊：
影响因子：
8.3
通讯作者：
Carmichael ST
中科院分区：
文献类型：
--
作者：
Rosenzweig S;Carmichael ST
Subcortical white matter stroke (WMS) constitutes up to 30% of all stroke subtypes. Mechanisms of oligodendrocyte and axon injury and repair play a central role in the damage and recovery following this type of stroke, and a comprehensive study of these processes requires a specialized experimental model that is different from common large artery, “gray matter” stroke models. Diminished recovery from stroke in aged patients implies that damage and repair processes are affected by advanced age, but such effects have not been studied in WMS. WMS was produced with focal microinjection of the vasoconstrictor L-NIO into the subcortical white matter ventral to the mouse forelimb motor cortex in young adult (2 months), middle aged (15 months) and aged mice (24 months). WMS produced localized oligodendrocyte cell death with higher numbers of apoptotic cells and greater oxidative damage in aged brains than in young-adult brains. Increased expression of MCP1 and TNFα in motor cortex neurons correlated with a more distributed microglial activation in aged brains 7 days after WMS. At 2 months aged mice displayed increased white matter atrophy and greater loss of corticostriatal connections compared to young-adult mice. Behavioral testing revealed an age-dependent exacerbation of forelimb motor deficits caused by the stroke, with decreased long-term functional recovery in aged animals. Age has a profound effect on the outcome of WMS, with more prolonged cell death and oxidative damage, increased inflammation, greater secondary white matter atrophy and a worse behavioral effect in aged vs young-adult mice.
