Action of SARS CoV2 in Human Brain Cultures

项目摘要 有新的证据表明，SARS-CoV 2或COVID 19进入人脑细胞，导致脑细胞的凋亡。 神经系统症状的后遗症。人们担心SARS-CoV 2可能导致神经毒性， 控制呼吸和心脏功能的大脑区域中的神经元死亡可能是一个促成因素。 急性心肺功能丧失和死亡的因素。SARS-CoV2可以通过以下方式进入大脑： 几种途径，包括通过鼻子，或神经支配受感染的肺组织或通过细胞内衬 大脑中的毛细血管COVID-19患者通常在发病前失去嗅觉或味觉， 呼吸道症状和一名患者在SARS检测呈阳性之前出现格林-巴利综合征- 冠状病毒2型似乎至少36%的COVID 19患者有神经系统表现，包括头痛， 恶心、意识丧失、中风、意识模糊、脑炎、脑膜炎和癫痫发作。这些临床 观察结果强烈表明SARS-CoV2在神经元死亡中的作用，重要的是大脑可能 是最早被感染的组织之一SARS-CoV2对大脑中不同细胞的作用， 以及在脑细胞中的感染性、向性和复制性尚不清楚。在本申请中，我们提出 评价：（1）SARS-CoV 2在人小胶质细胞、星形胶质细胞、神经元和 确定相对易感性？(2)细胞损伤的机制和评价潜在的保护 接近。(3)确定人类神经元对SARS CoV2感染的转录反应， 星形胶质细胞和小胶质细胞在单细胞水平，以获得新的见解，脑细胞的差异反应 到SARS CoV2，以更好地了解病毒引起的神经缺陷。

PROJECT SUMMARY There is emerging evidence that SARS-CoV2 or COVID19 gains entry into human brain cells leading to a sequela of neurologic symptoms. There is concern that SARS-CoV2 may lead to neurotoxicity and that neuronal death in the regions of the brain that control respiration and cardiac function may be a contributing factor to the acute loss of cardio respiratory function and death. SARS-CoV2 could gain access to the brain by several routes including through the nose, or neurons innervating infected lung tissue or through the cells lining blood capillaries in the brain. COVID-19 patients lose their sense of smell or taste often before the onset of respiratory symptoms and a patient presented with Guillain-Barré syndrome before testing positive for SARS- CoV2. It appears that at least 36% of COVID19 patients had neurologic manifestations including headache, nausea, loss of consciousness, strokes, confusion, encephalitis, meningitis and seizures. These clinical observations strongly indicate a role for SARS-CoV2 in the death of neurons and importantly the brain may be one of the first tissues infected and affected. The actions of SARS-CoV2 on the different cells in the brain, as well as the infectivity, tropism, and replication in brain cells is not yet known. In this application we propose to evaluate: (1) The tropism and replication of SARS-CoV2 in human microglia, astrocytes, neurons, and determine relative susceptibility? (2) The mechanisms of cellular injury and evaluate potential protective approaches. (3) Determine the transcriptional responses to SARS CoV2 infection in human neurons, astrocytes, and microglia at the single cell level to gain new insight into the differential response of brain cells to SARS CoV2 to better understand the neural deficits the virus causes.