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Review of "Caveolin-1 Mediates Neuroinflammation and Cognitive Impairment in SARS-CoV-2 Infection"

Reviewers: H Rus (University of Maryland) | 📘📘📘📘📘

Published onJul 02, 2024
Review of "Caveolin-1 Mediates Neuroinflammation and Cognitive Impairment in SARS-CoV-2 Infection"
key-enterThis Pub is a Review of
Caveolin-1 mediates neuroinflammation and cognitive impairment in SARS-CoV-2 infection
Caveolin-1 mediates neuroinflammation and cognitive impairment in SARS-CoV-2 infection
Description

Abstract Leukocyte infiltration of the CNS can contribute to neuroinflammation and cognitive impairment. Brain endothelial cells regulate adhesion, activation, and diapedesis of T cells across the blood-brain barrier (BBB) in inflammatory diseases. The integral membrane protein Caveolin-1 (Cav-1) critically regulates BBB permeability, but its influence on T cell CNS infiltration in respiratory viral infections is unknown. In this study, we sought to determine the role of Cav-1 at the BBB in neuroinflammation in a COVID-19 mouse model. We used mice genetically deficient in Cav-1 to test the role of this protein in T cell infiltration and cognitive impairment. We found that SARS-CoV-2 infection upregulated brain endothelial Cav-1. Moreover, SARS-CoV-2 infection increased brain endothelial cell vascular cell adhesion molecule-1 (VCAM-1) and CD3+ T cell infiltration of the hippocampus, a region important for short term learning and memory. Concordantly, we observed learning and memory deficits. Importantly, genetic deficiency in Cav-1 attenuated brain endothelial VCAM-1 expression and T cell infiltration in the hippocampus of mice with SARS-CoV-2 infection. Moreover, Cav-1 KO mice were protected from the learning and memory deficits caused by SARS-CoV-2 infection. These results indicate the importance of BBB permeability in COVID-19 neuroinflammation and suggest potential therapeutic value of targeting Cav-1 to improve disease outcomes.

To read the original manuscript, click the link above.

Summary of Reviews: The reviewer found the study strong, investigating Caveolin-1's role in neuroinflammation and cognitive impairment during SARS-CoV-2 infection. They highlighted the significant differences observed between wild-type and Cav-1 deficient mice, noting strong evidence for Cav-1's involvement in T-cell infiltration and memory deficits. While acknowledging some limitations in neurobehavioral testing and the need for further research, the reviewer emphasized the study's potential relevance to long COVID and its identification of a new target for improving outcomes in patients with neurological sequelae.

Reviewer 1 (Horia R…) | 📘📘📘📘📘

RR:C19 Strength of Evidence Scale Key

📕 ◻️◻️◻️◻️ = Misleading

📙📙 ◻️◻️◻️ = Not Informative

📒📒📒 ◻️◻️ = Potentially Informative

📗📗📗📗◻️ = Reliable

📘📘📘📘📘 = Strong

To read the reviews, click the links below. 

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