Ischemia-reperfusion impairs blood-brain barrier function and alters tight junction protein expression in the ovine fetus.
Ischemia-reperfusion impairs blood-brain barrier function and alters tight junction protein expression in the ovine fetus.
复制标题
DOI：
10.1016/j.neuroscience.2012.08.043
复制
发表时间：
2012-12-13
期刊：
影响因子：
3.3
通讯作者：
Stonestreet, B. S.
中科院分区：
文献类型：
--
作者：
Chen, X.;Threlkeld, S. W.;Cummings, E. E.;Juan, I.;Makeyev, O.;Besio, W. G.;Gaitanis, J.;Banks, W. A.;Sadowska, G. B.;Stonestreet, B. S.
血脑屏障是脑实质和血管内腔室之间的限制性界面。紧密连接有助于血脑屏障的完整性。缺氧缺血性血脑屏障损伤可能是胎儿脑损伤的重要组成部分。我们假设缺血后血脑屏障通透性的增加取决于再灌注的持续时间，紧密连接蛋白的减少与胎儿缺血相关的血脑屏障功能损害有关。采用Western免疫印迹法定量测定胎羊在妊娠127天无缺血、缺血后4、24、48小时的血脑转移常数（Ki）和紧密连接蛋白。缺血后4 h Ki升高幅度最大（P<0.05）。Occludin和claudin-5的表达在缺血后4小时下降，但在缺血后24和48小时恢复到对照水平。缺血后闭塞带-1和-2降低。Ki与紧密连接蛋白呈负相关，表明紧密连接蛋白的减少导致缺血后血脑屏障功能受损。我们得出结论，血脑屏障功能受损是胎儿缺氧缺血性脑损伤的重要组成部分，并且定量测量屏障通透性（Ki）变化的增加是缺血后再灌注时间的函数。通透性最大的增加发生在缺血后4小时，损伤后早期血脑屏障功能改善，因为血脑屏障的通透性在缺血后24小时和48小时比缺血后4小时要低。缺血后紧密连接分子组成的改变与血脑屏障通透性的增加有关。
The blood-brain barrier is a restrictive interface between the brain parenchyma and the intravascular compartment. Tight junctions contribute to the integrity of the blood-brain barrier. Hypoxic-ischemic damage to the blood-brain barrier could be an important component of fetal brain injury. We hypothesized that increases in blood-brain barrier permeability after ischemia depend upon the duration of reperfusion and that decreases in tight junction proteins are associated with the ischemia-related impairment in blood-brain barrier function in the fetus. Blood-brain barrier function was quantified with the blood-to-brain transfer constant (Ki) and tight junction proteins by Western immunoblot in fetal sheep at 127 days-of-gestation without ischemia, and 4-, 24-, or 48-h after ischemia. The largest increase in Ki (P<0.05) was 4-h after ischemia. Occludin and claudin-5 expressions decreased at 4-h, but returned toward control levels 24- and 48-h after ischemia. Zonula occludens-1 and -2 decreased after ischemia. Inverse correlations between Ki and tight junction proteins suggest that the decreases in tight junction proteins contribute to impaired blood-brain barrier function after ischemia. We conclude that impaired blood-brain barrier function is an important component of hypoxic-ischemic brain injury in the fetus, and that increases in quantitatively measured barrier permeability (Ki) change as a function of the duration of reperfusion after ischemia. The largest increase in permeability occurs 4-h after ischemia and blood-brain barrier function improves early after injury because the blood-brain barrier is less permeable 24- and 48- than 4-h after ischemia. Changes in the tight junction molecular composition are associated with increases in blood-brain barrier permeability after ischemia.
登录
查看更多内容
影响因子：
6.3
作者：
Lenzser, Gabor;Kis, Bela;Busija, David W.
通讯作者：
Busija, David W.
影响因子：
3.1
作者：
Cipolla, MJ;Crete, R;Rix, RD
通讯作者：
Rix, RD
影响因子：
12.7
作者：
Pfeiffer F;Schäfer J;Lyck R;Makrides V;Brunner S;Schaeren-Wiemers N;Deutsch U;Engelhardt B
通讯作者：
Engelhardt B
影响因子：
5.6
作者：
Fischer, S;Wiesnet, M;Schaper, W
通讯作者：
Schaper, W
影响因子：
2.9
作者：
Belayev, L;Busto, R;Ginsberg, MD
通讯作者：
Ginsberg, MD