Blast exposure elicits blood-brain barrier disruption and repair mediated by tight junction integrity and nitric oxide dependent processes.
Blast exposure elicits blood-brain barrier disruption and repair mediated by tight junction integrity and nitric oxide dependent processes.
复制标题
DOI：
10.1038/s41598-018-29341-6
复制
发表时间：
2018-07-27
影响因子：
4.6
通讯作者：
Cook DG
中科院分区：
文献类型：
--
作者：
Logsdon AF;Meabon JS;Cline MM;Bullock KM;Raskind MA;Peskind ER;Banks WA;Cook DG
轻度爆炸引起的创伤性脑损伤 (TBI) 与血脑屏障 (BBB) 破坏有关。然而，爆炸破坏血脑屏障完整性的机制尚不清楚。为了解决这个问题，在 0.25 至 72 小时的时间点对 10 个大脑区域的 BBB 对外周注射的 14C-蔗糖和 99mTc-白蛋白的通透性进行了量化。在小鼠中，重复 (2X) 爆炸会引发 BBB 对 14C-蔗糖的通透性，这种通透性在特定大脑区域持续 0.25 至 72 小时。然而，99mTc-白蛋白显示在同一时间间隔内存在双相 BBB 破坏（开放-封闭-开放），这在额叶皮层和海马体中最为明显。这表明爆炸启动了特定大脑区域中相互作用的血脑屏障破坏和修复过程。对延迟（72 小时）BBB 破坏的进一步研究表明，claudin-5 (CLD5) 的表达在海马中被破坏，但在背侧纹状体中没有，该区域没有表现出爆炸诱导的 BBB 对蔗糖或白蛋白的通透性。此外，我们发现一氧化氮合酶抑制剂 N(G)-硝基-L-精氨酸甲酯 (L-NAME) 可以阻断 BBB 通透性延迟和 CLD5 表达破坏。这些数据表明，潜在的一氧化氮依赖性信号通路启动了导致延迟 BBB 破坏的过程，这以大脑区域特定的方式表现出来。
Mild blast-induced traumatic brain injury (TBI) is associated with blood-brain barrier (BBB) disruption. However, the mechanisms whereby blast disrupts BBB integrity are not well understood. To address this issue BBB permeability to peripherally injected 14C-sucrose and 99mTc-albumin was quantified in ten brain regions at time points ranging from 0.25 to 72 hours. In mice, repetitive (2X) blast provoked BBB permeability to 14C-sucrose that persisted in specific brain regions from 0.25 to 72 hours. However, 99mTc-albumin revealed biphasic BBB disruption (open-closed-open) over the same interval, which was most pronounced in frontal cortex and hippocampus. This indicates that blast initiates interacting BBB disruption and reparative processes in specific brain regions. Further investigation of delayed (72 hour) BBB disruption revealed that claudin-5 (CLD5) expression was disrupted specifically in the hippocampus, but not in dorsal striatum, a brain region that showed no blast-induced BBB permeability to sucrose or albumin. In addition, we found that delayed BBB permeability and disrupted CLD5 expression were blocked by the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). These data argue that latent nitric oxide-dependent signaling pathways initiate processes that result in delayed BBB disruption, which are manifested in a brain-region specific manner.
登录
查看更多内容
影响因子：
17.1
作者：
Goldstein LE;Fisher AM;Tagge CA;Zhang XL;Velisek L;Sullivan JA;Upreti C;Kracht JM;Ericsson M;Wojnarowicz MW;Goletiani CJ;Maglakelidze GM;Casey N;Moncaster JA;Minaeva O;Moir RD;Nowinski CJ;Stern RA;Cantu RC;Geiling J;Blusztajn JK;Wolozin BL;Ikezu T;Stein TD;Budson AE;Kowall NW;Chargin D;Sharon A;Saman S;Hall GF;Moss WC;Cleveland RO;Tanzi RE;Stanton PK;McKee AC
通讯作者：
McKee AC
影响因子：
3
作者：
Hall AA;Mendoza MI;Zhou H;Shaughness M;Maudlin-Jeronimo E;McCarron RM;Ahlers ST
通讯作者：
Ahlers ST
影响因子：
4.8
作者：
Banks, William A.;Dohgu, Shinya;Vo, Than Q.
通讯作者：
Vo, Than Q.
影响因子：
2.9
作者：
Belayev, L;Busto, R;Ginsberg, MD
通讯作者：
Ginsberg, MD
DOI：
10.1073/pnas.0808698106
发表时间：
2009-02-10
影响因子：
11.1
作者：
Argaw, Azeb Tadesse;Gurfein, Blake T.;John, Gareth R.
通讯作者：
John, Gareth R.