BACKGROUND: Posterior circulation ischemia vertigo (PCIV) frequently presents with vestibular dysfunction in patients suffering from posterior circulation stroke. The conventional approaches often fail to address PCIV's complex pathophysiology, which involves neuroimmune dysregulation, hemodynamic abnormalities, and gut-brain axis disruption. Banxia Baizhu Tianma Decoction (BBTD), a traditional Chinese medicine, is employed in treating PCIV and vasogenic vertigo, but the mechanisms underlying its efficacy require further elucidation.
PURPOSE: This study examines the therapeutic mechanisms and efficacy of BBTD for PCIV, particularly focusing on its impacts on neuroinflammation, gut microbiota communities, and gut barrier using a rat model of PCIV.
METHODS: The chemical and bioactive constituents of BBTD were profiled using ULPLC-Q Exactive-Orbitrap-MS. The PCIV model was employed and treated with BBTD for 7 days. Neurological score was measured with balance beam test; cerebellar pathology was assessed by H&E and Nissl staining. The TTC staining was used to measure cerebral infarct volume. The levels of IL-6, IL-1β, and TNF-α in serum and cerebellar tissue was analyzed by ELISA. Its mechanisms were investigated by 16S rRNA sequencing, antibiotic antagonistic and fecal microbiota transplantation (FMT) experiments. Significant alterations in gut microbiota and their detailed mechanisms were identified. Intestinal barrier integrity was assessed by AB-PAS staining, tight junction proteins (MUC2, occludin, claudin-1, ZO-1), and colonic inflammatory cytokine levels. The levels of short-chain fatty acids in the cecal contents and cerebellar tissues of our experimental rats using gas chromatography-mass spectrometry (GC-MS).
RESULTS: Our findings demonstrated that BBTD significantly improved neurological function, ameliorates cerebral ischemia, and alleviated neuroinflammation in rats. Moreover, BBTD significantly modulated the diversity and composition of the gut microbiota, elevating Lactobacillus and Akkermansia, while reducing Clostridiales and Ruminococcaceae. The further antibiotic depletion and FMT experiments confirmed that gut microbiota was essential for BBTD-induced neuroinflammation and gut barrier protection in PCIV. BBTD ameliorated intestinal damage by enhancing acidic mucins and tight junction protein expression. BBTD treatment markedly increased the concentrations of propionic acid in intestinal fecal content and cerebellar tissue. Mechanistically, BBTD ameliorates ischemia-induced neuroinflammation and neuronal injury by modulating the TLR4-NF-κB-MyD88 pathway via the gut-brain axis.
CONCLUSION: BBTD ameliorates PCIV through gut-brain axis modulation, restoring gut barrier-microbiota balance and suppressing TLR4-NF-κB-MyD88 signaling. BBTD treatment and FMT may serve as an effective therapeutic strategy for mitigating posterior circulation ischemia progression.
