Blood-brain barrier (BBB) permeability can cause neuroinflammation and cognitive impairment. Caveolin-1 (Cav-1) critically regulates BBB permeability, but its influence on the BBB and consequent neurological outcomes in respiratory viral infections is unknown. We used Cav-1-deficient mice with genetically encoded fluorescent endothelial tight junctions to determine how Cav-1 influences BBB permeability, neuroinflammation, and cognitive impairment in mice with respiratory infection with ouse dapted (MA10) SARS-CoV-2 as a model for COVID-19. We found that SARS-CoV-2 infection increased brain endothelial Cav-1 and increased transcellular BBB permeability to albumin, decreased paracellular BBB Claudin-5 tight junctions, and caused T lymphocyte infiltration in the hippocampus, a region important for learning and memory. Concordantly, we observed learning and memory deficits in SARS-CoV-2 infected mice. Importantly, genetic deficiency in Cav-1 attenuated transcellular BBB permeability and paracellular BBB tight junction losses, T lymphocyte infiltration, and gliosis induced by SARS-CoV-2 infection. Moreover, Cav-1 KO mice were protected from the learning and memory deficits caused by SARS-CoV-2 infection. These results establish the contribution of Cav-1 to BBB permeability and behavioral dysfunction induced by SARS-CoV-2 neuroinflammation.

中文翻译：

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Caveolin-1 介导 SARS-CoV-2 感染中的血脑屏障通透性、神经炎症和认知障碍

血脑屏障（BBB）通透性可导致神经炎症和认知障碍。Caveolin-1 (Cav-1) 严格调节 BBB 通透性，但其对呼吸道病毒感染中 BBB 和后续神经系统结果的影响尚不清楚。我们使用具有基因编码荧光内皮紧密连接的 Cav-1 缺陷小鼠来确定 Cav-1 如何影响以适应 (MA10) SARS-CoV-2 为模型的呼吸道感染小鼠的 BBB 通透性、神经炎症和认知障碍。 2019冠状病毒病。我们发现，SARS-CoV-2感染增加了脑内皮Cav-1的含量，增加了跨细胞BBB对白蛋白的通透性，减少了细胞旁BBB Claudin-5紧密连接，并导致海马体（一个对学习和记忆很重要的区域）中T淋巴细胞浸润。同样，我们观察到 SARS-CoV-2 感染小鼠的学习和记忆缺陷。重要的是，Cav-1 的遗传缺陷减弱了 SARS-CoV-2 感染引起的跨细胞 BBB 通透性和细胞旁 BBB 紧密连接损失、T 淋巴细胞浸润和神经胶质增生。此外，Cav-1 KO 小鼠免受 SARS-CoV-2 感染引起的学习和记忆缺陷的影响。这些结果确定了 Cav-1 对 SARS-CoV-2 神经炎症引起的 BBB 通透性和行为功能障碍的贡献。