2. Academic Validation
  3. A Nurr1 agonist amodiaquine attenuates inflammatory events and neurological deficits in a mouse model of intracerebral hemorrhage

A Nurr1 agonist amodiaquine attenuates inflammatory events and neurological deficits in a mouse model of intracerebral hemorrhage

  • J Neuroimmunol. 2019 May 15;330:48-54. doi: 10.1016/j.jneuroim.2019.02.010.
Keita Kinoshita 1,  Kosei Matsumoto 2,  Yuki Kurauchi 2,  Akinori Hisatsune 3,  Takahiro Seki 2,  Hiroshi Katsuki 4
Affiliations

Affiliations

  • 1 Department of Chemico-Pharmacological Sciences, School of Pharmacy, Kumamoto University, Kumamoto 862-0973, Japan.
  • 2 Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
  • 3 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.
  • 4 Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan. Electronic address: hkatsuki@gpo.kumamoto-u.ac.jp.
PMID: 30825859 DOI: 10.1016/j.jneuroim.2019.02.010
Abstract

Inflammatory responses are considered to play pivotal roles in the pathogenesis of intracerebral hemorrhage (ICH). Here we show that a nuclear receptor Nurr1 (NR4A2) was expressed prominently in microglia/macrophages and astrocytes in the perihematomal region in the striatum of mice after ICH. Daily administration of a Nurr1 agonist amodiaquine (40 mg/kg, i.p.) from 3 h after ICH induction diminished perihematomal activation of microglia/macrophages and astrocytes. Amodiaquine also suppressed ICH-induced mRNA expression of IL-1β, CCL2 and CXCL2, and ameliorated motor dysfunction of mice. These results suggest that Nurr1 serves a novel target for ICH therapy.

Keywords

Astrocyte; Hemorrhagic stroke; Microglia; Motor dysfunction; Nuclear receptor.

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