ABSTRACT
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-1ß (IL-1ß) 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-1ß 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.
Subject(s)
Cerebral Small Vessel Diseases/immunology , Cerebral Small Vessel Diseases/psychology , Lipopolysaccharides/adverse effects , NF-kappa B/metabolism , Toll-Like Receptor 4/metabolism , Animals , Cerebral Small Vessel Diseases/chemically induced , Cerebral Small Vessel Diseases/drug therapy , Disease Models, Animal , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Male , NF-kappa B/genetics , Proline/analogs & derivatives , Proline/pharmacology , Proline/therapeutic use , Rats , Signal Transduction/drug effects , Sulfonamides/pharmacology , Sulfonamides/therapeutic use , Thiocarbamates/pharmacology , Thiocarbamates/therapeutic use , Toll-Like Receptor 4/genetics , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , Up-Regulation/drug effectsABSTRACT
Objective: To investigate the value of split hand in the differential diagnosis of amyotrophic lateral sclerosis(ALS) and cervical spondylotic amyotrophy (CSA). Methods: A total of 62 ALS patients, 57 CSA patients and 65 normal controls who visited the Neurology and Spine Department of Beijing Jishuitan Hospital from May 2013 to June 2017 were enrolled into this study.The amplitudes of compound muscle action potentials (CMAP) were recorded from abductor digiti minimi (ADM) and abductor pollicis brevis (APB). Moreover, the ratio of CMAP amplitude between ADM and APB (ADM/APB) was calculated. Results: The ADM/APB of the ALS group (1.93±1.97)was significantly higher than that of the normal control group (0.92±0.22)(P<0.05); the ADM/APB of the CSA group (0.74±0.32)was significantly lower than that of the normal control group (0.92±0.22)(P<0.05); the ADM/APB of the ALS group (1.93±1.97)was significantly higher than that of the CSA group(0.74±0.32)(P<0.05); the areas under receiver operator characteristic curve in patients with ALS was 0.843, the diagnostic sensitivity and specificity for ALS were 75.8% and 83.1% with the cutoff value of ADM/APB=1.077; the areas under receiver operator characteristic curve in patients with CSA was 0.737, the diagnostic sensitivity and specificity for CSA were 64.9% and 87.1% with the cutoff value of ADM/APB=0.739. Conclusion: The ADM/APB has certain clinical value for the differentiation of ALS and CSA.
