Skip to main content

Table 2 HMGB1-related findings in experimental models of epilepsy

From: HMGB1, neuronal excitability and epilepsy

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

  1. ↑ Increased, ↓ Decreased, CL Coriaria lactone, KA Kainic acid, DZP Diazepam, SE Status epilepticus, HMGB1 High mobility group box protein 1, mAb Monoclonal antibody, TLR4 Toll-like receptor 4, RAGE Receptors for advanced glycation end products, NF-κB Nuclear factor kappa-B, MCP-1 Monocyte chemotactic protein 1, CXCL-1 CXC chemokine ligands 1, iNOS Inducible nitric-oxide synthase, IL-6 Interleukin-6, COX-2 Cyclooxygenase-2, TNF-α Tumor necrosis factor-α, GL Glycyrrhizin, BBB Blood-brain-barrier, PND Postnatal days, SD Sprague-Dawley, EAE experimental autoimmune encephalitis