Experimental model | Animal strains or cell lines | Model phases | Main findings | References |
---|---|---|---|---|
CL-stimulated human microglial cell model | Human microglial cells | After the stimulation with CL | ↑HMGB1, TLR4, RAGE, NF-κB p65 and iNOS levels | Shi et al. [24], 2018 |
KA-induced acute and chronic seizures in mice | C57BL/6 mice and TLR4−/− C3H/HeJ mice | During acute and chronic seizures | ↑HMGB1 and TLR4 levels; TLR4−/− C3H/HeJ mice are resistant to KA-induced seizures | Maroso et al. [25], 2010 |
Sombati’s cell model and kainic acid-induced epilepsy model | SD rats | After 24 h and 72 h | ↑HMGB1 expression and translocation | Huang et al. [26], 2015 |
EAE model | 8-to-10-week-old male SD rats | During seizures | ↑HMGB1 expression; ↑activation of the TLR4/NF-kB signaling pathway | Liu et al. [27], 2017 |
Acute seizure models (maximal electroshock seizure, pentylenetetrazole-induced and kindling-induced), and chronic epilepsy model (KA-induced) | C57BL/6 mice (wild-type mice) and C57BL/10ScNJ mice (TLR4−/− mice) | During seizures | Anti-HMGB1 mAb treated: ↓seizure activities (dose-dependently with minimal side effects); ↓HMGB1 translocation; ↓seizure frequency; ↑cognitive function; The anti-seizure effect was absent in TLR4−/− mice | Zhao et al. [23], 2017 |
DZP-refractory SE | Male wild-type mice (C57BL/6 J) and TLR4−/− mice (C57BL/10ScNj) | During refractory SE period | ↑HMGB1 expression and translocation; Anti-HMGB1 mAb treated: ↓incidence of SE and the severity of seizure activity (TLR4-dependent pathway); Plasma HMGB1 level is closely correlated with the therapeutic response of anti-HMGB1 mAb | Zhao et al. [28], 2020 |
Pilocarpine-induced SE | Female C57BL/6 N mice | During status epilepticus | Anti-HMGB1 mAb treated: ↓BBB breakdown; ↓HMGB1 translocation; ↓MCP-1, CXCL-1, TLR4, and IL-6 in the hippocampus and cerebral cortex ↓apoptotic cells | Fu et al. [29], 2017 |
KA-induced SE | P21 male Wistar rats | During status epilepticus | ↑mRNA expression of IL-1β and TNF-α; ↑microglial activation; ↑neuronal damage in the hippocampus Anti-HMGB1 mAb treated: ↓synthesis of cytokines; ↓microglial activation; ↓neuronal losses in the hippocampus | Li et al. [30], 2013 |
KA-induced neuronal death model | Male BALB/c mice | GL 10 mg/kg, i.p. 30 min before KA administration | ↑neuronal death in both CA1 and CA3 regions of the hippocampus; GL treated: ↓COX-2, iNOS, and TNF-α; ↓gliosis; ↓neuronal death | Luo et al. [31], 2013 |
KA-induced seizure model | Male BALB/c mice | After 3 h, 6 h, 12 h, 4 d and 6 days | ↑HMGB1 expression and translocation; ↑HMGB1 serum concentration; GL treated: ↓HMGB1 expression and translocation; ↓HMGB1 serum concentration | Luo et al. [32], 2014 |
Lithium-pilocarpine-induced SE | Adult male SD rats | During status epilepticus | ↑HMGB1 expression and translocation; ↑HMGB1 serum concentration; ↑neuronal damage; ↑BBB disruption; GL treated: ↓HMGB1 expression and translocation; ↓HMGB1 serum concentration; ↓neuronal damage; ↓BBB disruption | Li et al. [33], 2019 |
KA-induced recurrent seizures model | P10 neonatal SD rats | At early (14 PND) and late (30 PND) time points | Celecoxib-treated: ↑time latency of seizures; ↓HMGB1 and TLR4 transcripts; ↓COX-2 protein expression | Morales-Sosa et al. [34], 2018 |
Pilocarpine-induced SE | SD rats | After 24 h | BoxA-treated: ↓IL-1β, IL-6 and TNF-α but not HMGB1; ↓BBB permeability; ↓hippocampal neuronal apoptosis; ↓hippocampal microglial activation; ↓TLR4, TLR2 | Yu et al. [35], 2019 |