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

S. Tang, L.-R. Yan, Z.-G. Ma, C. Ji

Department of Neurology, Beijing Jishuitan Hospital, Beijing, China. tangshu2000@sina.com

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• Neurology

OBJECTIVE: To explore the influences of toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) 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-κB-related proteins and inflammatory factors were detected. CSVD rats were treated with the TLR4/NF-κB pathway agonist and inhibitor to evaluate the regulatory effect of TLR4/NF-κB pathway on the expressions of TLR4, NF-κB p50 and NF-κB p65. Moreover, their influences on the cerebral edema, memory function and expressions of inflammatory factors [interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)] in CSVD rats were also analyzed.

RESULTS: In model group, the mRNA and protein expressions of TLR4 and NF-κB-related proteins in rat hippocampus were significantly higher than those in sham group (p<0.01), and the expressions of IL-1β and TNF-αsignificantly 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 NF-κB p50 and NF-κB 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-κB signaling pathway can restore memory function and reduce inflammatory response in CSVD rats.

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