Influences of the TLR4/NF-κB pathway on memory function and inflammatory factors in rats with cerebral small vessel disease

OBJECTIVE: To explore the influences of toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-kappa B) pathway on the memory function and inflammatory factors in rats with cerebral small vessel disease (CSVD). MATERIALS AND METHODS: CSVD model in rats was established. Expressions of TLR4/NF-kappa B-related proteins and inflammatory factors were detected. CSVD rats were treated with the TLR4/NF-kappa B pathway agonist and inhibitor to evaluate the regulatory effect of TLR4/NF-kappa B pathway on the expressions of TLR4, NF-kappa B p50 and NF-kappa B p65. Moreover, their influences on the cerebral edema, memory function and expressions of inflammatory factors [interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha)] in CSVD rats were also analyzed. RESULTS: In model group, the mRNA and protein expressions of TLR4 and NF-kappa B-related proteins in rat hippocampus were significantly higher than those in sham group (p<0.01), and the expressions of IL-1 beta and TNF-alpha significantly increased (p<0.05). The agonist lipopolysaccharide (LPS) significantly increased the proportion of TLR4-positive cells (p<0.01) and protein expression of TLR4 (p<0.01). The inhibitor CLI-095 obviously reduced the proportion of TLR4-positive cells and TLR4 expression (p<0.05). Pyrrolidine dithiocarbamate (PDTC) remarkably reduced the expressions of NE-kappa B p50 and NF-kappa B p65 in model group (p<0.05). LPS promoted cerebral edema, leading to memory dysfunction and enhanced inflammatory response in rats of model group. The inhibitor CLI-095+PDTC significantly reduced cerebral edema, lowered memory impairment and relieved inflammatory response in CSVD rats (p<0.05). CONCLUSIONS: The inhibitor of the TLR4/NF-kappa B signaling pathway can restore memory function and reduce inflammatory response in CSVD rats.