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A Triple Primary Cell Culture Model of the Human Blood-Brain Barrier for Studying Ischemic Stroke <em>In Vitro</em>

Ischemic stroke is a major cause of death and disability worldwide with limited therapeutic options. The neuropathology of ischemic stroke is ...

University of Miami

Neurological complications are common in patients affected by COVID-19 due to the ability of SARS-CoV-2 to infect brains. While the mechanisms of this process are not fully understood, it has been proposed that SARS-CoV-2 can infect the cells of the neurovascular unit (NVU), which form the blood-brain barrier (BBB). The aim of the current study was to analyze the expression pattern of the main SARS-CoV-2 receptors in naïve and HIV-1-infected cells of the NVU in order to elucidate a possible pathway of the virus entry into the brain and a potential modulatory impact of HIV-1 in this process.

Expression of SARS-CoV-2-related receptors in cells of the neurovascular unit: implications for HIV-1 infection.

We evaluated the mechanistic link between circadian rhythms and gut barrier permeability. Mice were subjected to either constant 24-h light (LL) or 12-h light/dark cycles (LD). Mice housed in LL experienced a significant increase in gut barrier permeability that was associated with dysregulated ß-catenin expression and altered expression of tight junction (TJ) proteins. Silencing of ß-catenin resulted in disruption of barrier function in SW480 cells, with ß-catenin appearing to be an upstream regulator of the core circadian components, such as Bmal1, Clock, and Per1/2. In addition, ß-catenin silencing downregulated ZO-1 and occludin TJ proteins with only limited or no changes at their mRNA levels, suggesting post transcriptional regulation. Indeed, silencing of ß-catenin significantly upregulated expression of matrix metallopeptidase (MMP)-2 and MMP-9, and blocking MMP-2/9 activity attenuated epithelial disruption induced by ß-catenin silencing. These results indicate the regulatory role of circadian disruption on gut barrier integrity and the associations between TJ proteins and circadian rhythms, while demonstrating the regulatory role of ß-catenin in this process.

Article	Year
Expression of SARS-CoV-2-related receptors in cells of the neurovascular unit: implications for HIV-1 infection. Journal of neuroinflammation\| PubMed ID: 34325716	2021
Circadian disruption alters gut barrier integrity via a ß-catenin-MMP-related pathway. Molecular and cellular biochemistry\| PubMed ID: 35976519	2022

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