SARS-CoV-2 Causes Brain Damage: Therapeutic Intervention with AZD8797
Küçük Resim Yok
Tarih
2023
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Oxford Univ Press
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Elevated CX3CL1 is associated with severe COVID-19 and neurologic symptoms. We aimed to investigate the potential protective effects of selective CX3CR1 antagonist AZD8797 on SARS-CoV-2-induced neuronal damage, and to identify the underlying mechanisms. K18-hACE2 transgenic mice (n = 37) were randomly divided into control groups and SARS-CoV-2 groups, with and without intraperitoneal administration of vehicle or AZD8797 (2.5 mg/mL/day), following exposure to either a single dose of SARS-CoV-2 inhalation or no exposure. Object recognition and hole board tests were performed to assess memory function. Postinfection 8 days, brain tissues were analyzed for histopathological changes, viral, glial, apoptotic, and other immunohistochemical markers, along with measuring malondialdehyde, glutathione, and myeloperoxidase activities. Serum samples were analyzed for proinflammatory cytokines. The SARS-CoV-2 group showed significant weight loss, neuronal damage, oxidative stress, and impaired object recognition memory, while AZD8797 treatment mitigated some of these effects, especially in weight, apoptosis, glutathione, and MCP-1. Histopathological analyses supported the protective effects of AZD8797 against SARS-CoV-2-induced damage. The CX3CL1-CX3CR1 signaling pathway could offer a promising target for reducing SARS-CoV-2's neurological impact, but additional research is needed to confirm these findings in combination with other therapies and assess the clinical significance.
Açıklama
Anahtar Kelimeler
Covid-19, Cx3cl1, Histology, Oxidative Stress, Transgenic Mice
Kaynak
Microscopy and Microanalysis
WoS Q Değeri
N/A
Scopus Q Değeri
Q3
Cilt
29
Sayı
6
