Lactobacillus acidophilus Exerts Neuroprotective Effects in Mice with Traumatic Brain Injury

Abstract

ABSTRACT Background Traumatic brain injury (TBI) causes dysbiosis and intestinal barrier disruption, which further exacerbate brain damage via an inflammatory pathway. Gut microbiota remodeling by Lactobacillus acidophilus (LA) is a potential intervention. Objective The aim of this study was to investigate the neuroprotective effects of LA in TBI and elucidated underlying mechanisms. Methods C57BL/6 male mice (aged 8–9 wk) were subjected to weight-drop impact and gavaged with saline (TBI + vehicle) or LA (1 × 1010 CFU) (TBI + LA) on the day of injury and each day after for 1, 3, or 7 d. The sham + vehicle mice underwent craniotomy without brain injury and were gavaged with saline. Sensorimotor functions were determined pre-TBI and 1, 3, and 7 d postinjury. Indexes of neuroinflammation, peripheral inflammation, and intestinal barrier function were measured on days 3 and 7. Microbiota composition was measured 3 d postinjury. The data were mainly analyzed by 2-factor ANOVA. Results Compared with sham + vehicle mice, the TBI + vehicle mice exhibited impairments in the neurological severity score (+692%, day 3; +600%, day 7) and rotarod test (−58%, day 3; −45%, day 7) (P < 0.05), which were rescued by LA. The numbers of microglia (total and activated) and astrocytes and concentrations of TNF-α and IL1-β in the perilesional cortex were elevated in the TBI + vehicle mice on day 3 or 7 compared with sham + vehicle mice (P < 0.05) and were normalized by LA. Compared with sham + vehicle mice, the TBI + vehicle mice exhibited increased serum concentrations of endotoxin and TNF-α, and intestinal barrier permeability (D-lactate) on days 3 and 7 (P < 0.05), and these changes were alleviated by LA. Three days postinjury, the microbiota composition was disrupted in the TBI + vehicle mice compared with sham + vehicle mice (P < 0.05), which was restored by LA. Conclusion Our results demonstrate that LA exerts neuroprotective effects that may be associated with gut microbiota remodeling in TBI mice.