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Investigation of the effects of SARS-CoV-2 infection of neurons and astrocytes on neuroinflammation using 3D bioprinted neural tissue

Grant number: 20/11374-2
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): October 01, 2020
Effective date (End): March 31, 2022
Field of knowledge:Biological Sciences - Morphology - Cytology and Cell Biology
Principal Investigator:Marimélia Aparecida Porcionatto
Grantee:Eduardo Henrique Backes
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated research grant:20/05289-2 - In vitro and in silico modeling of COVID-19, AP.R

Abstract

Besides the severe damage to the respiratory system, studies have shown the effects of COVID-19 on the Central Nervous System (CNS) in patients with severe infection. Around 30% of all severe COVID-19 patients show neurological complications. The main neurological symptoms are headaches, seizures and consciousness loss, and necropsies of infected patients showing neural degeneration. The infection can result in severe neurological complications such as Viral Encephalitis, Toxic Encephalopathy, and acute cerebrovascular disease. At least two mechanisms can explain the damage to the CNS: i) SARS-CoV-2 can cross the blood-brain-barrier, as already described for other viroses; or ii) SARS-CoV-2 can directly infect the CNS, through olphactory neurons, as it was detected in the cerebrospinal fluid and axonal transport was shown for other Coronaviruses. Therefore, the studies of invasion mechanisms and their consequences are fundamental to understanding effects on the CNS. For this study, we will use 3D bioprinted neural tissue composed of biomaterial and h-iPSC differentiated in neurons and astrocytes. After infection of the bioprinted neural tissue by SARS-CoV-2 we will evaluate astrocytes response by the quantitation of anti and proinflammatory citokines, followed by testing drugs that act on neuroinflammation. (AU)