Application of a Human Blood Brain Barrier Organ-on-a-Chip Model to Evaluate Small Molecule Effectiveness against Venezuelan Equine Encephalitis Virus.
Application of a Human Blood Brain Barrier Organ-on-a-Chip Model to Evaluate Small Molecule Effectiveness against Venezuelan Equine Encephalitis Virus.
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DOI：
10.3390/v14122799
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发表时间：
2022-12-15
期刊：
影响因子：
--
通讯作者：
Narayanan A
中科院分区：
文献类型：
--
作者：
Boghdeh NA;Risner KH;Barrera MD;Britt CM;Schaffer DK;Alem F;Brown JA;Wikswo JP;Narayanan A
血脑屏障（BBB）是一个多细胞微环境，在调节中枢神经系统（CNS）的双向转运中起重要作用。已知许多急性感染性病毒如甲病毒和黄病毒的感染会影响BBB内皮衬里的完整性。通过气溶胶途径感染委内瑞拉马脑炎病毒（VEEV）会对BBB的完整性造成严重损害，这会导致长期的神经系统后遗症。理想地，有效的治疗干预策略应不仅控制宿主中的病毒载量，而且还预防和/或逆转BBB处的有害事件。二维单一培养物，包括使用内皮细胞的跨孔模型，并不能概括BBB复杂的多细胞环境。复杂的体外器官芯片模型（OOC）为引入类人实验模型提供了很好的机会，以了解疾病状态的机制基础，并以高度相关的方式评估候选治疗药物的有效性。在这里，我们证明了神经血管单位（NVU）在分析VEEV感染后感染和促炎反应的动力学和omaveloxolone的治疗有效性，以保持BBB的完整性和减少病毒和炎症负荷的效用。
The blood brain barrier (BBB) is a multicellular microenvironment that plays an important role in regulating bidirectional transport to and from the central nervous system (CNS). Infections by many acutely infectious viruses such as alphaviruses and flaviviruses are known to impact the integrity of the endothelial lining of the BBB. Infection by Venezuelan Equine Encephalitis Virus (VEEV) through the aerosol route causes significant damage to the integrity of the BBB, which contributes to long-term neurological sequelae. An effective therapeutic intervention strategy should ideally not only control viral load in the host, but also prevent and/or reverse deleterious events at the BBB. Two dimensional monocultures, including trans-well models that use endothelial cells, do not recapitulate the intricate multicellular environment of the BBB. Complex in vitro organ-on-a-chip models (OOC) provide a great opportunity to introduce human-like experimental models to understand the mechanistic underpinnings of the disease state and evaluate the effectiveness of therapeutic candidates in a highly relevant manner. Here we demonstrate the utility of a neurovascular unit (NVU) in analyzing the dynamics of infection and proinflammatory response following VEEV infection and therapeutic effectiveness of omaveloxolone to preserve BBB integrity and decrease viral and inflammatory load.
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影响因子：
4
作者：
Creelan BC;Gabrilovich DI;Gray JE;Williams CC;Tanvetyanon T;Haura EB;Weber JS;Gibney GT;Markowitz J;Proksch JW;Reisman SA;McKee MD;Chin MP;Meyer CJ;Antonia SJ
通讯作者：
Antonia SJ
DOI：
10.3390/v12091021
发表时间：
2020-09-13
期刊：
Viruses
影响因子：
--
作者：
Bakovic A;Bhalla N;Kortchak S;Sun C;Zhou W;Ahmed A;Risner K;Klimstra WB;Narayanan A
通讯作者：
Narayanan A
影响因子：
7.2
作者：
Daneman, Richard;Prat, Alexandre
通讯作者：
Prat, Alexandre
影响因子：
--
作者：
Hu L;Cao Y;Chen H;Xu L;Yang Q;Zhou H;Li J;Yu Q;Dou Z;Li Y;Yan F;Liu F;Chen G
通讯作者：
Chen G
影响因子：
7.5
作者：
Alcendor DJ;Block FE 3rd;Cliffel DE;Daniels JS;Ellacott KL;Goodwin CR;Hofmeister LH;Li D;Markov DA;May JC;McCawley LJ;McLaughlin B;McLean JA;Niswender KD;Pensabene V;Seale KT;Sherrod SD;Sung HJ;Tabb DL;Webb DJ;Wikswo JP
通讯作者：
Wikswo JP