Inflammation in Primary Human Astrocytes is Dependent on Toll-Like Receptor 3 & 9 When Exposed to Astrocyte-Derived Exosomes Isolated from Patients with COVID-19 and TBI

There have been 775 million confirmed cases of SARS-CoV-2 infections worldwide. With each SARS-CoV-2 infection the patient has a chance of developing an array of chronic symptoms referred to as Long-COVID. These symptoms include fatigue, brain fog, anxiety, and depression. These symptoms could be the result of chronic inflammation of glial brain cells caused by Blood-Brain-Barrier disruption. Astrocytes are one of these glial cells involved in maintaining the Blood-Brain-Barrier. We hypothesize that the Astrocyte cells are packaging up and sending out pro-inflammatory “cargo” via exosomes that can then be taken up by other cells, inducing an inflammation phenotype.

We believe that participants who have a combined history of COVID-19 and mTBI will produce more pro-inflammatory “cargo” and better be able to transmit an inflammatory phenotype. In order to determine through which receptor this neuroinflammatory phenotype is being transmitted, we selected 5 Toll-Like Receptors on Primary Human Astrocyte cells to treat with drug inhibitors. We found that inhibition of Toll-Like Receptor 3 and 9 blocked the transmission of an inflamed phenotype to the astrocyte cell. This finding will open the possibility of future studies into the use of current Toll-Like Receptor 3 & 9 inhibitory drugs for the prevention of glial cell inflammation.