Ischemic Injury to White Matter: An Age-Dependent Process
Ischemic Injury to White Matter: An Age-Dependent Process
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DOI：
10.1177/1073858408324788
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发表时间：
2009-04-01
期刊：
影响因子：
5.6
通讯作者：
Baltan, Selva
中科院分区：
文献类型：
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作者：
Baltan, Selva
缺血性中风的风险随着年龄的增长而急剧增加，尽管其原因尚未探索。白色物质（WM）和灰质构成大脑的相等比例，并且WM在大多数中风中受损。轴索损伤和功能障碍是导致中风后临床缺陷相关残疾的主要原因。作者最近报道，在老年小鼠中，中枢神经系统WM固有地更容易受到缺血性损伤，并且WM损伤的机制随着年龄的变化而变化。老年小鼠的缺血性WM损伤主要是由Ca（2+）非依赖性兴奋性毒性介导的，涉及AMPA/红藻氨酸受体的过度激活。谷氨酸释放，由于反向谷氨酸转运，发生更早，是更强大的老年小鼠显示上调GLT 1，主要的谷氨酸转运蛋白。阻断NMDA受体不能改善年轻小鼠缺血后的WM功能，但能减轻老年小鼠的缺血性损伤。本研究更新的主要目标是总结等效脑损伤随年龄增长而引起更多损伤的证据，并强调年龄在任何成功的中风治疗中的重要性。
The risk for ischemic stroke increases drastically with age, although reasons for this remain unexplored. White matter (WM) and gray matter constitute equal proportions of the brain, and WM is injured in most strokes. Axonal injury and dysfunction are responsible for much of the disability associated with clinical deficits observed after stroke. The authors recently reported that central nervous system WM is inherently more vulnerable to ischemic injury in older mice, and the mechanisms of WM injury change as a function of age. Ischemic WM injury in older mice is predominately mediated by a Ca(2+)-independent excitotoxicity involving overactivation of AMPA/kainate receptors. Glutamate release, due to reverse glutamate transport, occurs earlier and is more robust in older mice that show up-regulation of GLT1, the main glutamate transporter. Blockade of NMDA receptors does not improve WM function after ischemia in the young but aggravates ischemic injury in older mice. The main goals of this research update are to summarize the evidence for equivalent brain insults inducing more damage with aging, and to highlight the importance of age in any successful stroke therapy.