Caveolin-1 mediates blood-brain barrier permeability, neuroinflammation, and cognitive impairment in SARS-CoV-2 infection

J Neuroimmunol. 2024 Mar 15:388:578309. doi: 10.1016/j.jneuroim.2024.578309. Epub 2024 Feb 4.


Blood-brain barrier (BBB) permeability can cause neuroinflammation and cognitive impairment. Caveolin-1 (Cav-1) critically regulates BBB permeability, but its influence on the BBB and consequent neurological outcomes in respiratory viral infections is unknown. We used Cav-1-deficient mice with genetically encoded fluorescent endothelial tight junctions to determine how Cav-1 influences BBB permeability, neuroinflammation, and cognitive impairment following respiratory infection with mouse adapted (MA10) SARS-CoV-2 as a model for COVID-19. We found that SARS-CoV-2 infection increased brain endothelial Cav-1 and increased transcellular BBB permeability to albumin, decreased paracellular BBB Claudin-5 tight junctions, and caused T lymphocyte infiltration in the hippocampus, a region important for learning and memory. Concordantly, we observed learning and memory deficits in SARS-CoV-2 infected mice. Importantly, genetic deficiency in Cav-1 attenuated transcellular BBB permeability and paracellular BBB tight junction losses, T lymphocyte infiltration, and gliosis induced by 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 establish the contribution of Cav-1 to BBB permeability and behavioral dysfunction induced by SARS-CoV-2 neuroinflammation.

Keywords: Blood-brain barrier; Brain; CD3; Caveolin-1; Claudin-5; Endothelial; Neuroinflammation; Novel object recognition; SARS-CoV-2; T cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Brain Barrier / metabolism
  • COVID-19* / complications
  • Caveolin 1 / genetics
  • Caveolin 1 / metabolism
  • Cognitive Dysfunction* / etiology
  • Memory Disorders / etiology
  • Mice
  • Neuroinflammatory Diseases
  • Permeability
  • SARS-CoV-2 / metabolism


  • Caveolin 1
  • Cav1 protein, mouse