ADMSC-derived Exosome-facilitated Ciprofloxacin Therapy Improves Neurological Outcomes in E. coli-infected Rodents
Han-Tan Chai, Kuan-Hung Chen, Yi-Ling Chen, Chi-Ruei Huang, Hon-Kan YipIntroduction:
Bacterial meningitis remains a major cause of neurological morbidity, with limited treatment efficacy due to inflammation and oxidative damage. This study investigated whether exosomes derived from adipose-derived mesenchymal stem cells (ADMSC-Exo) could enhance the neuroprotective effects of ciprofloxacin (CIP) against Escherichia coli-induced brain injury in rats.
Methods:
In vitro, N2a neuroblastoma cells were co-treated with lipopolysaccharide (LPS, 50 ng/mL), CIP (20 µM), and/or ADMSC-Exo (5 µg) to assess cellular damage, inflammatory markers, and apoptosis. In vivo, rats (n=50) were divided into five groups: (1) sham control, (2) E. coli implantation, (3) E. coli + CIP (3 mg/kg, i.v. for 5 days), (4) E. coli + ADMSC-Exo (100 µg, i.v. on Days 0, 1, and 3), and (5) E. coli + CIP + ADMSC-Exo. Neurological outcomes, infection area, and protein expression of inflammatory, apoptotic, and oxidative stress markers were evaluated.
Results:
LPS exposure markedly increased DNA damage, cellular senescence, and expression of inflammatory and apoptotic proteins, which were significantly reduced by either CIP or ADMSCExo, and most effectively by their combination (all p<0.01). In vivo, the combined treatment group (Group 5) showed the smallest infection area, lowest mortality, and greatest suppression of inflammatory (IL-1β, IL-6, TNF-α, MMP9), apoptotic (cleaved-Caspase-3, cleaved-PARP), and oxidative stress (NOX-1, NOX-2) proteins (all p<0.0001).
Conclusion:
Combined CIP and ADMSC-Exo therapy offers superior protection against E. coliinduced brain injury, highlighting its potential as a novel adjunctive treatment for bacterial meningitis.