Therapeutic effects of anti-HMGB1 monoclonal antibody on pilocarpine-induced status epilepticus in mice

• Published in: Scientific reports Vol. 7; no. 1; pp. 1179 - 13
• Main Authors: Fu, Li, Liu, Keyue, Wake, Hidenori, Teshigawara, Kiyoshi, Yoshino, Tadashi, Takahashi, Hideo, Mori, Shuji, Nishibori, Masahiro
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26.04.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 13/2; 13/51; 14/19; 14/63; 38; 38/77; 631/154; 64/60; 692/617/375/178; 82; Animal models; Apoptosis; Astrocytes; Blood-brain barrier; Cerebral cortex; Epilepsy; HMGB1 protein; Humanities and Social Sciences; Inflammation; Interleukin 6; Latency; Membrane permeability; Microglia; Monoclonal antibodies; Monocyte chemoattractant protein 1; multidisciplinary; Permeability; Pilocarpine; Rodents; Science; Science (multidisciplinary); Scopolamine; Seizures; Translocation
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-01325-y

Inflammatory processes in brain tissue have been described in human epilepsy of various etiologies and in experimental models of seizures. High mobility group box-1 (HMGB1) is now recognized as representative of damage-associated molecular patterns (DAMPs). In the present study, we focused on whether anti-HMGB1 antibody treatment could relieve status epilepticus- triggered BBB breakdown and inflammation response in addition to the seizure behavior itself. Pilocarpine and methyl-scopolamine were used to establish the acute seizure model. Anti-HMGB1 mAb showed inhibitory effects on leakage of the BBB, and on the HMGB1 translocation induced by pilocarpine. The expression of inflammation-related factors, such as MCP-1, CXCL-1, TLR-4, and IL-6 in hippocampus and cerebral cortex were down-regulated by anti-HMGB1 mAb associated with the number of activated astrocytes, microglial cells as well as the expression of IL-1β. Both hematoxylin & eosin and TUNEL staining showed that the apoptotic cells could be reduced after anti-HMGB1 mAb treatment. The onset and latency of Racine stage five were significantly prolonged in the anti-HMGB1 mAb group. These results suggested that anti-HMGB1 mAb prevented the BBB permeability, reduced HMGB1 translocation while inhibiting the expression of inflammation-related factors, protected against neural cell apoptosis and prolonged Racine stage 5 seizure onset and latency.