New insights into the neurological effects of COVID-19

Wood, Heather

doi:10.1038/s41582-020-0386-7

Cited by 25 publications

(22 citation statements)

References 3 publications

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“…Overall, these data suggest that there may be some tropism for SARS-CoV-2 in the brain of WT mice, supporting some reports of neurological issues in humans with COVID-19. 55 We also observed sex differences in K18 hACE2 transgenic mice with males exhibiting a TH1 and TH17 phenotype at 4-DPI whereas female K18 hACE2 transgenic mice had a TH2 responses at the same time point, similar to studies of acute LPSinduced inflammation, 28,29 which suggests that males may be more prone to exhibit neurological problems during SARS-CoV-2 infection, independent of viral load.…”

Section: Perlman S Mccray Personal Communication June 2020)supporting

confidence: 71%

Lethality of SARS-CoV-2 infection in K18 human angiotensin converting enzyme 2 transgenic mice

Oladunni

Park

Tamayo

et al. 2020

Preprint

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Vaccine and antiviral development against SARS-CoV-2 infection or COVID-19 disease currently lacks a validated small animal model. Here, we show that transgenic mice expressing human angiotensin converting enzyme 2 (hACE2) by the human cytokeratin 18 promoter (K18 hACE2) represent a susceptible rodent model. K18 hACE2-transgenic mice succumbed to SARS-CoV-2 infection by day 6, with virus detected in lung airway epithelium and brain. K18 ACE2-transgenic mice produced a modest TH1/2/17 cytokine storm in the lung and spleen that peaked by day 2, and an extended chemokine storm that was detected in both lungs and brain. This chemokine storm was also detected in the brain at day 4. K18 hACE2-transgenic mice are, therefore, highly susceptible to SARS-CoV-2 infection and represent a suitable animal model for the study of viral pathogenesis, and for identification and characterization of vaccines (prophylactic) and antivirals (therapeutics) for SARS-CoV-2 infection and associated severe COVID-19 disease.

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Section: Perlman S Mccray Personal Communication June 2020)supporting

confidence: 71%

Lethality of SARS-CoV-2 infection in K18 human angiotensin converting enzyme 2 transgenic mice

Oladunni

Park

Tamayo

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…Some patients with COVID-19 have developed Guillain–Barré syndrome ( 7 ). These findings suggest that neuronal damage may concern not only the olfactory system and brainstem nuclei, as was initially suggested ( 8 ).…”

supporting

confidence: 70%

Parkinson's Disease in the Era of a Novel Respiratory Virus Pandemic

et al. 2020

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“…Our results provide insight into the mechanism of progression of peripheral inflammatory responses into the CNS as well as a glimpse into the timing for the initiation of microglial activation, which leads to neuroinflammation. These findings as such are applicable to peripheral inflammation-induced neurological complications wherein there is no direct CNS infection [61] but which primarily develop and progress due to the prevailing SIRS [60,62]. Our finding that the peripheral inflammatory factors initially affecting the CECs could be more relevant in the context that CEC function can be modulated by systemically administered drugs to block the progression of peripheral inflammation into the CNS.…”

Section: Discussionmentioning

confidence: 61%

Temporal unsnarling of brain’s acute neuroinflammatory transcriptional profiles reveals panendothelitis as the earliest event preceding microgliosis

2020

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Sepsis-associated encephalopathy (SAE) is an acutely progressing brain dysfunction induced by systemic inflammation. The mechanism of initiation of neuroinflammation during SAE, which ultimately leads to delirium and cognitive dysfunction, remains elusive. We aimed to study the molecular events of SAE to capture its onset and progression into the central nervous system (CNS), and further identify the cellular players involved in mediating acute inflammatory signaling. Gene expression profiling on the cerebral vessels isolated from the brains of the mice treated with peripheral lipopolysaccharide (LPS) revealed that the cerebral vasculature responds within minutes to acute systemic inflammation by upregulating the expression of immediate early response genes, followed by activation of the nuclear factor-κB pathway. To identify the earliest responding cell type, we used fluorescence-activated cell sorting (FACS) to sort the glial and vascular cells from the brains of the mice treated with LPS at different time points, and RNA-seq was performed on microglia and cerebral endothelial cells (CECs). Bioinformatic analysis followed by further validation in all the cell types revealed that panendothelitis. i.e., the activation of CECs is the earliest event in the CNS during the inception of acute neuroinflammation. Microglial activation occurs later than that of CECs, suggesting that CECs are the most likely initial source of proinflammatory mediators, which could further initiate glial cell activation. This is then followed by the activation of apoptotic signaling in the CECs, which is known to lead to the blood–brain barrier disruption and allow peripheral cytokines to leak into the CNS, exacerbate the gliosis, and result in the vicious neuroinflammatory cascade. Together, our results model the earliest sequential events during the advancement of systemic inflammation into the CNS and facilitate to understand the interplay between the vascular and glial cells in initiating and driving acute neuroinflammation during SAE.

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New insights into the neurological effects of COVID-19

Cited by 25 publications

References 3 publications

Lethality of SARS-CoV-2 infection in K18 human angiotensin converting enzyme 2 transgenic mice

Lethality of SARS-CoV-2 infection in K18 human angiotensin converting enzyme 2 transgenic mice

Parkinson's Disease in the Era of a Novel Respiratory Virus Pandemic

Temporal unsnarling of brain’s acute neuroinflammatory transcriptional profiles reveals panendothelitis as the earliest event preceding microgliosis

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