Resilience of females to acute blood-brain barrier damage and anxiety behavior following mild blast traumatic brain injury.
Resilience of females to acute blood-brain barrier damage and anxiety behavior following mild blast traumatic brain injury.
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DOI：
10.1186/s40478-022-01395-8
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发表时间：
2022-06-27
影响因子：
7.1
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中科院分区：
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低强度爆炸暴露可能会导致军事人员的神经损伤。目前，缺乏实验数据，使用性别作为生物变量的神经血管的结果后，爆炸暴露。为了模拟轻度冲击创伤性脑损伤（mbTBI），使用McMillan冲击装置将雄性和雌性大鼠暴露于单个11 psi静态峰值超压冲击波，然后在冲击后6 h、24 h、7 d和14 d对群组实施安乐死，随后分离杏仁核。在mbTBI后，动物立即经历心动过缓，尽管没有观察到氧饱和度水平的变化或体重减轻。与雄性假手术组相比，雄性mbTBI动物显示出显著更高水平的焦虑样行为（旷场和高架十字迷宫）;然而，雌性mbTBI动物中没有焦虑表型。通过测量紧密连接（TJ）蛋白（闭合小带-1（ZO-1）、闭合蛋白和封闭蛋白-5）、胶质细胞酸性蛋白（GFAP）和血脑屏障（BBB）周围星形胶质细胞末端足覆盖的表达来探索爆炸诱导的神经血管损伤。蛋白质印迹分析表明，TJ蛋白水平显着降低，在6小时和24小时后mbTBI的雄性大鼠，但不是在雌性大鼠，与假手术相比。雌性动物在mbTBI后6小时GFAP降低，而雄性动物在mbTBI后24小时显示GFAP表达降低。在mbTBI后7天，两种性别的组间TJ或GFAP水平均无显著差异。在mbTBI后24小时，男性mbTBI后BBB周围的血管完整性和星形胶质细胞终足覆盖率显著降低。这些结果表明，GFAP表达的损失可能是由于在BBB的星形胶质细胞损伤。我们的研究结果还证明了单次mbTBI后急性血管和行为结果的性别差异。与雄性动物相比，雌性动物在mbTBI后表现出缺乏BBB病理学，对应于改善的急性神经心理学结果。在线版本包含补充材料，可通过10.1186/s40478-022-01395-8获得。
Low-level blast exposure can result in neurological impairment for military personnel. Currently, there is a lack of experimental data using sex as a biological variable in neurovascular outcomes following blast exposure. To model mild blast traumatic brain injury (mbTBI), male and female rats were exposed to a single 11 psi static peak overpressure blast wave using the McMillan blast device and cohorts were then euthanized at 6 h, 24 h, 7 d and 14 d post-blast followed by isolation of the amygdala. After mbTBI, animals experience immediate bradycardia, although no changes in oxygen saturation levels or weight loss are observed. Male mbTBI animals displayed significantly higher levels of anxiety-like behavior (open field and elevated plus maze) compared to male sham groups; however, there was no anxiety phenotype in female mbTBI animals. Blast-induced neurovascular damage was explored by measuring expression of tight junction (TJ) proteins (zonula occludens-1 (ZO-1), occludin and claudin-5), glial fibrillary acidic protein (GFAP) and astrocyte end-feet coverage around the blood–brain barrier (BBB). Western blot analysis demonstrates that TJ protein levels were significantly decreased at 6 h and 24 h post-mbTBI in male rats, but not in female rats, compared to sham. Female animals have decreased GFAP at 6 h post-mbTBI while male animals display decreased GFAP expression at 24 h post-mbTBI. By 7 d post-mbTBI, there were no significant differences in TJ or GFAP levels between groups in either sex. At 24 h post-mbTBI, vascular integrity and astrocytic end-feet coverage around the BBB was significantly decreased in males following mbTBI. These results demonstrate that loss of GFAP expression may be due to astrocytic damage at the BBB. Our findings also demonstrate sex differences in acute vascular and behavioral outcomes after single mbTBI. Female animals display a lack of BBB pathology after mbTBI corresponding to improved acute neuropsychological outcomes as compared to male animals. The online version contains supplementary material available at 10.1186/s40478-022-01395-8.
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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：
--
作者：
Hubbard WB;Greenberg S;Norris C;Eck J;Lavik E;VandeVord P
通讯作者：
VandeVord P
影响因子：
3
作者：
Dickerson MR;Murphy SF;Urban MJ;White Z;VandeVord PJ
通讯作者：
VandeVord PJ
影响因子：
3.4
作者：
Heyburn, Lanier;Abutarboush, Rania;Sajja, Venkata Siva Sai Sujith
通讯作者：
Sajja, Venkata Siva Sai Sujith
影响因子：
4.6
作者：
Logsdon AF;Meabon JS;Cline MM;Bullock KM;Raskind MA;Peskind ER;Banks WA;Cook DG
通讯作者：
Cook DG