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

Abstract 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...

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Autores principales:	Li Fu, Keyue Liu, Hidenori Wake, Kiyoshi Teshigawara, Tadashi Yoshino, Hideo Takahashi, Shuji Mori, Masahiro Nishibori
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6df81a8a50254fc58a102a06ba381d8b
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spelling	oai:doaj.org-article:6df81a8a50254fc58a102a06ba381d8b2021-12-02T11:40:51ZTherapeutic effects of anti-HMGB1 monoclonal antibody on pilocarpine-induced status epilepticus in mice10.1038/s41598-017-01325-y2045-2322https://doaj.org/article/6df81a8a50254fc58a102a06ba381d8b2017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01325-yhttps://doaj.org/toc/2045-2322Abstract 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.Li FuKeyue LiuHidenori WakeKiyoshi TeshigawaraTadashi YoshinoHideo TakahashiShuji MoriMasahiro NishiboriNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Li Fu Keyue Liu Hidenori Wake Kiyoshi Teshigawara Tadashi Yoshino Hideo Takahashi Shuji Mori Masahiro Nishibori Therapeutic effects of anti-HMGB1 monoclonal antibody on pilocarpine-induced status epilepticus in mice
description	Abstract 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.
format	article
author	Li Fu Keyue Liu Hidenori Wake Kiyoshi Teshigawara Tadashi Yoshino Hideo Takahashi Shuji Mori Masahiro Nishibori
author_facet	Li Fu Keyue Liu Hidenori Wake Kiyoshi Teshigawara Tadashi Yoshino Hideo Takahashi Shuji Mori Masahiro Nishibori
author_sort	Li Fu
title	Therapeutic effects of anti-HMGB1 monoclonal antibody on pilocarpine-induced status epilepticus in mice
title_short	Therapeutic effects of anti-HMGB1 monoclonal antibody on pilocarpine-induced status epilepticus in mice
title_full	Therapeutic effects of anti-HMGB1 monoclonal antibody on pilocarpine-induced status epilepticus in mice
title_fullStr	Therapeutic effects of anti-HMGB1 monoclonal antibody on pilocarpine-induced status epilepticus in mice
title_full_unstemmed	Therapeutic effects of anti-HMGB1 monoclonal antibody on pilocarpine-induced status epilepticus in mice
title_sort	therapeutic effects of anti-hmgb1 monoclonal antibody on pilocarpine-induced status epilepticus in mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/6df81a8a50254fc58a102a06ba381d8b
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Therapeutic effects of anti-HMGB1 monoclonal antibody on pilocarpine-induced status epilepticus in mice

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