Chiang Wesley, Stout Angela, Yanchik-Slade Francine, Li Herman, Terrando Niccolò, Nilsson Bradley L, Gelbard Harris A, Krauss Todd D
Department of Biochemistry and Biophysics, Center for Neurotherapeutics Discovery and Department of Neurology, and Departments of Pediatrics, Neuroscience, and Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York 14642, United States.
Department of Chemistry and The Institute of Optics, University of Rochester, Rochester, New York 14627, United States.
ACS Appl Nano Mater. 2023 Aug 7;6(16):15094-15107. doi: 10.1021/acsanm.3c02719. eCollection 2023 Aug 25.
Despite limited evidence for infection of SARS-CoV-2 in the central nervous system, cognitive impairment is a common complication reported in "recovered" COVID-19 patients. Identification of the origins of these neurological impairments is essential to inform therapeutic designs against them. However, such studies are limited, in part, by the current status of high-fidelity probes to visually investigate the effects of SARS-CoV-2 on the system of blood vessels and nerve cells in the brain, called the neurovascular unit. Here, we report that nanocrystal quantum dot micelles decorated with spike protein (COVID-QDs) are able to interrogate neurological damage due to SARS-CoV-2. In a transwell co-culture model of the neurovascular unit, exposure of brain endothelial cells to COVID-QDs elicited an inflammatory response in neurons and astrocytes without direct interaction with the COVID-QDs. These results provide compelling evidence of an inflammatory response without direct exposure to SARS-CoV-2-like nanoparticles. Additionally, we found that pretreatment with a neuro-protective molecule prevented endothelial cell damage resulting in substantial neurological protection. These results will accelerate studies into the mechanisms by which SARS-CoV-2 mediates neurologic dysfunction.
尽管有证据表明严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染中枢神经系统的情况有限，但认知障碍是“康复”的冠状病毒病（COVID-19）患者中常见的并发症。确定这些神经损伤的根源对于指导针对它们的治疗设计至关重要。然而，这类研究在一定程度上受到高保真探针现状的限制——高保真探针用于直观研究SARS-CoV-2对大脑中血管和神经细胞系统（即神经血管单元） 的影响时。在此，我们报告称，用刺突蛋白修饰的纳米晶体量子点胶束（COVID-QDs）能够探究SARS-CoV-2引起的神经损伤情况。在神经血管单元的Transwell共培养模型中, 脑内皮细胞暴露于COVID-QDs会引发神经元和星形胶质细胞的炎症反应，而无需与COVID-QDs直接相互作用。这些结果为在未直接接触SARS-CoV-2样纳米颗粒的情况下发生炎症反应提供了令人信服的证据。此外，我们发现用一种神经保护分子进行预处理可防止内皮细胞损伤，从而产生实质性的神经保护作用。这些结果将加速对SARS-CoV-2介导神经功能障碍机制的研究。
