Center for Memory and Aging, University of New Mexico, Albuquerque, NM 87106, USA.
Department of Neurology, University of New Mexico, Albuquerque, NM 87106, USA.
Int J Mol Sci. 2022 May 5;23(9):5150. doi: 10.3390/ijms23095150.
Though COVID-19 is primarily characterized by symptoms in the periphery, it can also affect the central nervous system (CNS). This has been established by the association between stroke and COVID-19. However, the molecular mechanisms that cause stroke related to a COVID-19 infection have not been fully explored. More specifically, stroke and COVID-19 exhibit an overlap of molecular mechanisms. These similarities provide a way to better understand COVID-19 related stroke. We propose here that peripheral macrophages upregulate inflammatory proteins such as matrix metalloproteinases (MMPs) in response to SARS-CoV-2 infection. These inflammatory molecules and the SARS-CoV-2 virus have multiple negative effects related to endothelial dysfunction that results in the disruption of the blood-brain barrier (BBB). Finally, we discuss how the endothelial blood-brain barrier injury alters central nervous system function by leading to astrocyte dysfunction and inflammasome activation. Our goal is to elucidate such inflammatory pathways, which could provide insight into therapies to combat the negative neurological effects of COVID-19.
虽然 COVID-19 主要表现为外周症状，但它也可能影响中枢神经系统 (CNS)。这一点已经通过中风与 COVID-19 之间的关联得到证实。然而，导致 COVID-19 感染相关中风的分子机制尚未得到充分探索。更具体地说，中风和 COVID-19 表现出分子机制的重叠。这些相似之处为更好地理解 COVID-19 相关中风提供了途径。我们在这里提出，外周巨噬细胞在 SARS-CoV-2 感染时上调炎症蛋白，如基质金属蛋白酶 (MMPs)。这些炎症分子和 SARS-CoV-2 病毒对内皮功能障碍有多种负面影响，导致血脑屏障 (BBB) 破坏。最后，我们讨论了内皮血脑屏障损伤如何通过导致星形胶质细胞功能障碍和炎症小体激活来改变中枢神经系统功能。我们的目标是阐明这些炎症途径，这可能为对抗 COVID-19 的负面神经影响的治疗方法提供启示。
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