White matter vulnerability to ischemic injury increases with age because of enhanced excitotoxicity
White matter vulnerability to ischemic injury increases with age because of enhanced excitotoxicity
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DOI：
10.1523/jneurosci.5137-07.2008
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发表时间：
2008-02-06
影响因子：
5.3
通讯作者：
Ransom, Bruce R.
中科院分区：
文献类型：
--
作者：
Baltan, Selva;Besancon, Elaine F.;Ransom, Bruce R.
中风的发病率随着年龄的增长而增加，这归因于血管因素。我们在这里表明，中枢神经系统白色物质（WM）本质上是更容易受到缺血性损伤的老年动物和WM损伤的机制作为一个功能的年龄。用小鼠视神经研究WM功能。老年动物（12个月）的WM功能不能通过去除细胞外Ca 2+或阻断反向Na+/Ca 2+交换来保护缺血性损伤，就像年轻成年人一样。老年小鼠缺血性WM损伤主要由谷氨酸释放和AMPA/红藻氨酸型谷氨酸受体激活介导。谷氨酸释放，归因于反向谷氨酸转运，发生更早，是更强大的老年小鼠表现出更大的表达谷氨酸转运蛋白。WM对缺血性损伤的脆弱性是年龄依赖性的，这一观察结果可能对其他年龄相关的CNS疾病的发病机制产生影响。
Stroke incidence increases with age and this has been attributed to vascular factors. We show here that CNS white matter (WM) is intrinsically more vulnerable to ischemic injury in older animals and that the mechanisms of WM injury change as a function of age. The mouse optic nerve was used to study WM function. WM function in older animals (12 months) was not protected from ischemic injury by removal of extracellular Ca2+ or by blockade of reverse Na+/Ca2+ exchange, as is the case with young adults. Ischemic WM injury in older mice is predominately mediated by glutamate release and activation of AMPA/kainate-type glutamate receptors. Glutamate release, attributable to reverse glutamate transport, occurs earlier and is more robust in older mice that show greater expression of the glutamate transporter. The observation that WM vulnerability to ischemic injury is age dependent has possible implications for the pathogenesis of other age-related CNS conditions.