Probiotic Supplementation Modulates FGFR2 and TLR4 Signaling and Attenuates Chronic Neuroinflammation in an Experimental Stroke Model

چکیده مقاله

Stroke is a major cause of mortality and morbidity. It is known to induce gut dysbiosis, which can exacerbate brain injury by increasing systemic inflammation and disrupting the gut-brain axis. This study investigated the effects of probiotics on immunomodulation and brain regeneration in a post-stroke animal model, with a particular focus on gut-brain axis. In this study, Male Wistar rats were divided into three groups: Sham, Ischemia and Ischemia+Probiotic. Focal cerebral ischemia was induced by one-hour middle cerebral artery occlusion (MCAO). The probiotic group received 109 CFU/ml probiotic solution via gavage for 14 days. After 14 days, behavioral outcomes and cerebral infarct volume were assessed. Molecular docking was performed to analyze the binding affinities of probiotic metabolites with TLR4 and FGFR2 which were further validated by RT-PCR gene expression analysis. Serum matrix metalloproteinase-9 activity was evaluated using zymography and oxidative stress was assessed by measuring malondialdehyde, total antioxidant capacity, and nitric oxide levels in the ischemic penumbra. According to the results, the probiotic group showed a significant reduction in infarct volume and improved behavioral deficits. Molecular analysis revealed that probiotics increased nitric oxide levels and total antioxidant capacity while decreasing malondialdehyde levels. Consistent with molecular docking, there was a significant increase in FGFR2 and TLR4 gene expression and matrix metalloproteinase-9 activity. These findings show probiotic supplementation reduces brain damage after stroke, likely via the modulation of FGFR2/TLR4 inflammatory pathway, which could originate from gut microenvironment dysregulation.