Lactobacillus paracasei effectively protects neuronal function in severe traumatic brain injury in rats by...

Traumatic brain injury (TBI) is a growing public health concern with a high mortality rate. Our previous study identified Lactobacillus paracasei L9 (LP) as a promising neuroprotective agent. This study aimed to investigate the changes in neural function and gut barrier function in TBI rats after LP intervention and elucidate its protective role and mechanism in TBI.

A rat model of severe TBI was established based on weight loss. Neurological function score, immunofluorescence staining of NeuN⁺, Iba-1⁺, and CD68⁺ cells in brain tissue, dry-wet weight method for brain water content, Evans blue for blood-brain barrier permeability, real-time qPCR for occludin, Zonula Occludens-1 (ZO-1), intercellular Adhesion Molecule-1 (ICAM-1), toll-like receptor 4 (TLR4)/Myeloid differentiation primary response 88 (Myd88) expression in brain and intestinal tissue, and ELISA for inflammatory factors, LPS, and flagellin expression were evaluated at 1, 3, and 7 days post-injury.

LP administration significantly improved behavioral performance on days 3 and 7 post-TBI, increased NeuN⁺ cells, decreased Iba-1⁺ and CD68⁺ cells, reduced brain edema, decreased Evans blue content, enhanced tight junction proteins in the damaged cortex, and reduced inflammatory factor expression. In the intestine, LP intervention improved villus height and crypt depth, upregulated occludin and ZO-1 mRNA expression, downregulated ICAM-1, and reduced the serum levels of D-Lac and LPS. In addition, the LP group exhibited lower TLR4 and Myd88 expression levels in the brain.

LP protects against TBI-induced neuronal dysfunction by restoring the gut barrier, suppressing systemic inflammation, and inhibiting cortical TLR4/Myd88, supporting its potential as an adjuvant therapy.