Effects of aging on blood brain barrier and matrix metalloproteases following controlled cortical impact in mice.
Effects of aging on blood brain barrier and matrix metalloproteases following controlled cortical impact in mice.
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DOI：
10.1016/j.expneurol.2011.12.016
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发表时间：
2012-03
影响因子：
5.3
通讯作者：
Berman, Nancy E. J.
中科院分区：
文献类型：
--
作者：
Lee, Phil;Kim, Jieun;Williams, Rachel;Sandhir, Rajat;Gregory, Eugene;Brooks, William M.;Berman, Nancy E. J.
关键词：
衰老会改变大脑对损伤的反应能力。成年人和老年人大脑之间的主要区别之一是，类似的损伤会导致老年人大脑中更大的血脑屏障破坏。这些研究的目的是利用高场强度MRI T1定位来量化年龄对血脑屏障通透性的影响，并确定在老年C57/Bl6小鼠脑损伤后，基质金属蛋白酶及其抑制剂的激活或血脑屏障结构蛋白、occludin、小带occludin -1 （ZO-1）和claudin-5的表达是否发生改变。T1图谱研究显示，在控制性皮质冲击后，老年人（21-15个月）大脑的血脑屏障通透性高于成人（4-6个月）。免疫组化IgG证实脑膜周血脑屏障通透性增加。MMP-9活性在老年大脑皮层受控制后增加，并伴有MMP-9基因表达的增加。MMP-2活性在未损伤的老年脑组织中高于成人脑组织。两组脑损伤后Occludin和ZO-1 mRNA水平均无变化，但老年脑损伤后claudin-5 mRNA水平低于成人。这些结果表明，损伤后老年脑血脑屏障通透性定量增加，伴随MMP-9激活增加和血脑屏障修复反应下降。
Aging alters the ability of the brain to respond to injury. One of the major differences between the adult and aged brain is that comparable injuries lead to greater blood brain barrier disruption in the aged brain. The goals of these studies were to quantify the effects of age on BBB permeability using high field strength MRI T1 mapping and to determine whether activation of matrix metalloproteases, their inhibitors, or expression of blood brain barrier structural proteins, occludin, zonnula occludins-1 (ZO-1) and claudin-5 were altered following injury to the aged C57/Bl6 mouse brain. T1 mapping studies revealed greater blood brain barrier permeability in the aged (21–15 months old) brain than in the adult (4–6 months old) following controlled cortical impact. The increased blood brain barrier permeability in the pericontusional region was confirmed with IgG immunohistochemistry. MMP-9 activity was increased following controlled cortical impact in the aged brain, and this was accompanied by increased MMP-9 gene expression. MMP-2 activity was higher in the uninjured aged brain than in the adult brain. Occludin and ZO-1 mRNA levels were unchanged following injury in either age group, but claudin-5 mRNA levels were lower in the aged than the adult brain following injury. These results demonstrate quantitative increases in blood brain barrier permeability in the aged brain following injury that are accompanied by increased MMP-9 activation and decreased blood brain barrier repair responses.
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