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SARS-CoV-2 Causes Brain Damage: Therapeutic Intervention with AZD8797
Elif Kervancioglu Demirci1, Engin Alp Onen2, Erva Sevic Yilmaz1
1Histology and Embryology Department, Istanbul Faculty of Medicine, Istanbul University, Turgut Ozal Cd. No:118m, Capa-Fatih, Istanbul 34093, Turkey.
Summary
The CX3CL1-CX3CR1 pathway may worsen COVID-19 neurological damage. AZD8797, a CX3CR1 antagonist, showed protective effects in mice, reducing neuronal damage and improving memory. Further research is needed for clinical application.
Area of Science:
- Neuroscience
- Virology
- Pharmacology
Background:
- Elevated CX3CL1 levels correlate with severe COVID-19 and neurological complications.
- The CX3CL1-CX3CR1 signaling pathway is implicated in neuroinflammation and viral pathogenesis.
Purpose of the Study:
- To evaluate the neuroprotective potential of the CX3CR1 antagonist AZD8797 against SARS-CoV-2-induced neuronal damage.
- To elucidate the underlying mechanisms of AZD8797's effects in a mouse model.
Main Methods:
- K18-hACE2 transgenic mice were exposed to SARS-CoV-2 and treated with AZD8797 or vehicle.
- Cognitive function was assessed using object recognition and hole board tests.
- Brain tissues and serum were analyzed for histopathology, viral load, glial activation, apoptosis, oxidative stress markers, and cytokines.
Main Results:
- SARS-CoV-2 infection led to weight loss, neuronal damage, oxidative stress, and memory impairment.
- AZD8797 treatment partially reversed these effects, improving weight, reducing apoptosis, and enhancing glutathione levels.
- Histopathological analysis confirmed AZD8797's protective role against SARS-CoV-2-induced brain injury.
Conclusions:
- The CX3CL1-CX3CR1 pathway is a potential therapeutic target for mitigating SARS-CoV-2 neurological sequelae.
- AZD8797 demonstrates promising neuroprotective effects in a preclinical model of COVID-19.
- Further investigation is warranted to confirm clinical efficacy and explore combination therapies.
