Laquinimod and 3,3'-diindolylemethane alleviate neuropathological events and neurological deficits in a mouse model of intracerebral hemorrhage

Kosei Matsumoto; Keita Kinoshita; Ayaka Yoshimizu; Yuki Kurauchi; Akinori Hisatsune; Takahiro Seki; Hiroshi Katsuki

doi:10.1016/j.jneuroim.2020.577195

Laquinimod and 3,3'-diindolylemethane alleviate neuropathological events and neurological deficits in a mouse model of intracerebral hemorrhage

J Neuroimmunol. 2020 Feb 20:342:577195. doi: 10.1016/j.jneuroim.2020.577195. Online ahead of print.

Authors

Kosei Matsumoto¹, Keita Kinoshita¹, Ayaka Yoshimizu¹, Yuki Kurauchi¹, Akinori Hisatsune², Takahiro Seki¹, Hiroshi Katsuki³

Affiliations

¹ Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences and School of Pharmacy, Kumamoto University, Kumamoto 862-0973, Japan.
² Priority Organization for Innovation and Excellence, Kumamoto University, Kumamoto 860-8555, Japan; Program for Leading Graduate Schools "HIGO (Health life science: Interdisciplinary and Glocal Oriented) Program", Kumamoto University, Kumamoto 862-0973, Japan.
³ Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences and School of Pharmacy, Kumamoto University, Kumamoto 862-0973, Japan. Electronic address: hkatsuki@gpo.kumamoto-u.ac.jp.

PMID: 32120083
DOI: 10.1016/j.jneuroim.2020.577195

Abstract

We examined the effects of compounds shown to activate aryl hydrocarbon receptor (AhR) signaling on a mouse model of intracerebral hemorrhage (ICH). Daily oral administration of laquinimod (25 mg/kg) or 3,3'-diindolylmethane (250 mg/kg) from 3 h after ICH induction improved motor functions, prevented the decrease of neurons within the hematoma, and attenuated activation of microglia/macrophages and astrocytes in the perihematomal region as well as infiltration of neutrophils into the hematoma. Elevated expression of AhR was detected in microglia and neutrophils, and both drugs inhibited upregulation of interleukin-6 and CXCL1. These results propose AhR as a therapeutic target for ICH.

Keywords: Aryl hydrocarbon receptor; Astrocyte; Hemorrhagic stroke; Microglia; Neutrophil.