Prolonged antibiotic treatment accelerates neurological recovery and reduces long-term neuroinflammatory gene expression after experimental TBI in mice

BACKGROUND: Neuroprotective effects of antibiotic medications are reported in the context of experimental traumatic brain injury (TBI), but the choice of substances and treatment intervals are inconsistent. METHODS: In this study, we tested whether continuous posttraumatic administration of a combined broad-spectrum antibiotic regimen of vancomycin, amoxicillin, and clavulanic acid affects neurological recovery, structural brain damage and neuroinflammation following experimental TBI by controlled cortical impact in 80 adult male C57BL/6 mice. RESULTS: Antibiotic treatment led to accelerated recovery from posttraumatic neuromotor impairment and exploratory behavioural disorders. Reduced astrocytic activation and neuronal loss in the ipsilesional thalamic region in the early (5 days post injury, dpi) and attenuated neuroinflammatory gene expression in the late (30 dpi) period were observed alongside a severe disruption of the intestinal microbial spectrum after five days of antibiotic treatment, while the structural brain damage remained unaffected. CONCLUSION: We demonstrated accelerated neurological recovery and long-lasting effects of antibiotic treatment on the neuroinflammatory response after experimental TBI. Increased plasma levels of lipopolysaccharide-binding protein and short-chain fatty acids were evaluated, yet not identified as potential modulators. As the observed effects can not entirely be linked to the intestinal dysbiosis, direct modulation of secondary brain damage by the antibiotic substances should be considered as an alternate mechanism.