Abstract
This study aimed to investigate the association of serum high-mobility group box-1 (HMGB1) and toll-like receptor 4 (TLR4) expressions with the risk of epilepsy as well as their correlations with disease severity and resistance to anti-epilepsy drugs. One hundred and five epilepsy patients and 100 healthy controls (HCs) were enrolled in this case-control study, and serum samples were collected from all participants to assess the HMGB1 and TLR4 expressions by enzyme-linked immunosorbent assay (ELISA). Both serum HMGB1 (P<0.001) and TLR4 (P<0.001) expressions were higher in epilepsy patients than in HCs, and they displayed good predictive values for risk of epilepsy. Moreover, HMGB1 was positively correlated with TLR4 level (r=0.735, P<0.001). HMGB1 and TLR4 levels were both elevated in patients with an average seizure duration >5 min compared to patients with a seizure duration ≤5 min (P=0.001 and P=0.014, respectively). Also, HMGB1 and TLR4 were increased in patients with seizure frequency >3 times per month compared to patients with seizure frequency ≤3 times per month (both P=0.001). In addition, HMGB1 and TLR4 expressions were higher in intractable cases compared to drug-responsive cases (P<0.001). In conclusion, both HMGB1 and TLR4 expressions were correlated with increased risk and severity of epilepsy and their level was higher in patients resistant to anti-epilepsy drugs.
Highlights
Epilepsy, which is characterized by unprovoked and recurrent seizures, is a common brain disorder associated with elevated mortality rate, decreased social participation, as well as declined quality of life [1,2,3]
We investigated the correlation of serum High-mobility group box-1 (HMGB1) and toll-like receptor 4 (TLR4) levels with risk of epilepsy in this case-control study and we found that: i) expressions of HMGB1 and TLR4 were higher in epilepsy patients compared with healthy controls (HCs); ii) elevated HMGB1 and TLR4 expressions were both associated with longer seizure duration as well as increased seizure frequency; iii) increased HMGB1 and TLR4 expressions were correlated with higher possibility of anti-epilepsy drugs resistance
They discovered that seizure frequency increased 2.5-fold with HMGB1 overexpression in the mice model, which was due to the elevated activation of the TLR4HMGB1 pathway
Summary
Epilepsy, which is characterized by unprovoked and recurrent seizures, is a common brain disorder associated with elevated mortality rate, decreased social participation, as well as declined quality of life [1,2,3]. Among the members of the TLRs family, toll-like receptor 4 (TLR4), which is a lipopolysaccharide-sensing receptor that triggers inflammation by inducing gene transcription, has attracted great attention in various diseases [10]. As to TLR4, the resistance of kainite-induced seizures has been observed in TLR4 knockout mice [13,14,15,16,17]. Most of these previous studies investigating the function of HMGB1 and TLR4 in epilepsy were performed in experimental animal models or brain specimens; few clinical studies have
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