期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 97, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.intimp.2021.107695
关键词
Brain abscess; Ciprofloxacin; Dexamethasone; Inflammation; Microglia; S; aureus
资金
- Indian Council of Medical Research (ICMR), New Delhi, India [3/1/3/JRF-2016/LS/HRD-37 (40488)]
Staphylococcus aureus-induced brain abscess is a critical health issue in developing countries, and traditional surgical intervention is not effective. This study explores the relationship between TLR-2 and GR as a potential alternative therapeutic strategy for brain abscess treatment. Results suggest that combination therapy of ciprofloxacin and dexamethasone significantly reduces bacterial burden and abscess area under TLR-2 blocking conditions, leading to improvements in behavioral impairments.
Staphylococcus aureus induced brain abscess is a critical health concern throughout the developing world. The conventional surgical intervention could not regulate the abscess-induced brain inflammation. Thus further study over the alternative therapeutic strategy for treating a brain abscess is of high priority. The resident glial cells recognize the invading S. aureus by their cell surface Toll-like receptor-2 (TLR-2). Glucocorticoid receptor (GR) was known for its immunosuppressive effects. In this study, an attempt had been taken to utilize the functional relationship or cross-talking between TLR-2 and GR during the pathogenesis of brain abscesses. Here, the combination of an antibiotic (i.e. ciprofloxacin) and dexamethasone was used to regulate the brain inflammation either in TLR-2 or GR blocking condition. We were also interested to figure out the possible impact of alternative therapy on behavioral impairments. The results indicated that combination treatment during TLR-2 blockade significantly reduced the bacterial burden and abscess area score in the infected brain. However, marked improvements were observed in anxiety, depression-like behavior, and motor co-ordination. The combination treatment after TLR-2 blocking effectively scavenged free radicals (H2O2, superoxide anion, and NO) through modulating antioxidant enzyme activities that ultimately control S. aureus induced glial reactivity possibly via up-regulating GR expression. The exogenous dexamethasone might regulate the GR expression in the brain by increasing the corticosterone concentration and the GC-GR mediated signaling. Therefore, this in-vivo study demonstrates the possible regulatory mechanism of bacterial brain abscess that involved TLR-2 and GR as a part of neuroendocrine-immune interaction.
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