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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 units (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.  The gene and protein expression profile of ACE2, TMPRSS2, ADAM17, BSG, DPP4, AGTR2, ANPEP, cathepsin B and cathepsin L was assessed by qPCR and immunoblotting, respectively. In addition, we investigated if brain endothelial cells can be affected by the exposure to the S1 subunit of the S protein, the domain responsible for the direct binding of SARS-CoV-2 to the ACE2 receptors.  The receptors involved in SARS-CoV-2 infection are coexpressed in the cells of the NVU, especially in astrocytes and microglial cells. These receptors are functionally active as exposure of endothelial cells to the SARS CoV-2 S1 protein subunit altered the expression pattern of tight junction proteins, such as claudin-5 and ZO-1. Additionally, HIV-1 infection upregulated ACE2 and TMPRSS2 expression in brain astrocytes and microglia cells.  These findings provide key insight into SARS-CoV-2 recognition by cells of the NVU and may help to develop possible treatment of CNS complications of COVID-19.

Expression of SARS-CoV-2-related Receptors in Cells of the Neurovascular Unit: Implications for HIV-1 Infection.

The blood-brain barrier (BBB) is essential for the homeostasis of the central nervous system (CNS). Functions of the BBB are performed by the neurovascular unit (NVU), which consists of endothelial cells, pericytes, astrocytes, microglia, basement membrane, and neurons. NVU cells interact closely and together are responsible for neurovascular coupling, BBB integrity, and transendothelial fluid transport. Studies have shown that NVU dysfunction is implicated in several acute and chronic neurological diseases, including Alzheimer's disease, multiple sclerosis, and stroke. The mechanisms of NVU disruption remain poorly understood, partially due to difficulties in selective targeting of NVU cells. In this review, we discuss the relative merits of available protein markers and drivers of the NVU along with recent advancements that have been made in the field to increase efficiency and specificity of NVU research.

In Vivo Targeting of the Neurovascular Unit: Challenges and Advancements.

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.

Article	Year
Expression of SARS-CoV-2-related Receptors in Cells of the Neurovascular Unit: Implications for HIV-1 Infection. Research square\| PubMed ID: 33655239	2021
In Vivo Targeting of the Neurovascular Unit: Challenges and Advancements. Cellular and molecular neurobiology\| PubMed ID: 34086179	2022
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

Oandy Naranjo

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