Table 3.
Summary of findings reporting HMGB1 in epilepsy.
| S.N. | Intervention | Model | Mechanism | Observations | Reference |
|---|---|---|---|---|---|
| 1 | HMGB1 | KA-induced seizure in mice | • Targeting HMGB1/TLR4 axis | • ↑ Frequency of seizure and total duration • Seizure can be ↓ by TLR4 and HMGB1 antagonists | Maroso et al., 2010 |
| 2 | Anti-HMGB1 mAb | Acute seizure (MES and PTZ); Chronic seizure by KA in mice | • Inhibition of HMGB1 translocation | • ↓ Seizure threshold; ↓ time in tonic–clonic seizures and ↓ death • Delayed onset of generalized seizures; ↓ seizure stage; ↓ incidence of tonic seizures | Zhao et al., 2017 |
| 3 | Molecular isoforms of HMGB1 | Electrically induced Se in rats | • Activation of HMGB1/TLR4 axis | • ↑ level of HMGB1 and its acetylated and disulphide isoforms in blood | Walker et al., 2017 |
| 4 | HMGB1 | Pilocarpine-induced SE in rats | • Regulation of P-gp expression via RAGE/NF-κB inflammatory signaling pathways | • ↓ The expression levels of MDR1A/B mRNA and P-gp protein | Xie et al., 2017 |
| 5 | HMGB1 | KA-induced epilepsy in rats | • Modulation of glutamate metabolism | • ↑ Extracellular HMGB1 suggesting contribution of HMGB1 in epilepsy related hyperexcitability • Translocation of HMGB1from nucleus to cytosol after KA administration | Kaneko et al., 2017 |
| 6 | HMGB1 | Pilocarpine-induced epilepsy in rats | • Targeting HMGB1 via TLR4/NF-kB signaling pathway | • Inhibit the development of AE-related epilepsy • Suppression of HMGB1 expression • MiR-129-5p mediated TLR4/NF-kB signaling pathway ameliorated AE-related epilepsy | Liu et al., 2017 |
| 7 | Anti-HMGB1 mAb | Pilocarpine-induced SE in mice | • Inhibition of HMGB1 release and inflammation | • Protection of BBB permeability; ↓ HMGB1 translocation • ↓ Latency and frequency of stage 5 seizures | Fu et al., 2017 |
| 8 | Molecular isoforms of HMGB1 | Human | • Evaluation of HMGB1 isoforms as mechanistic biomarkers of epileptogenesis in sera obtained from epileptic patients | • HMGB1 isoforms in the brain and blood were changed • Expression of disulphide HMGB1 in newly diagnosed epilepsy patients | Walker et al., 2017 |
S.N., serial number; ↑, increased; ↓, decreased; BBB, blood–brain barrier; Pgp, P-glycoprotein; MES, maximal electroshock seizures; KA, kainic acid; PTZ, pentylenetetrazol; HMGB1, high mobility group box 1; EEG, electroencephalogram; MDR1A/B, multidrug resistance protein 1A/B; RAGE, receptor for advanced glycation end products; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; miR-129-5p, micro RNA-129-5p; qRT-PCR, quantitative real-time polymerase chain reaction; AE, autoimmune encephalitis; mAb, monoclonal antibody; PRNCs, primary rats neural cells.