Pretreatment with low-dose fimasartan ameliorates NLRP3 inflammasome-mediated neuroinflammation and brain injury after intracerebral hemorrhage

Xiuli Yang, Jing Sun, Tae Jung Kim, Young Ju Kim, Sang Bae Ko, Chi Kyung Kim, Xiaofeng Jia, Byung Woo Yoon

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, which is composed of an NLRP3 domain, the adaptor molecule apoptosis-associated speck-like protein containing a CARD (ASC) domain, and procaspase-1, plays an important role in the immune pathophysiology of the secondary damage induced by intracerebral hemorrhage (ICH). This study aims to investigate whether pre-stroke treatment with fimasartan, an angiotensin II receptor blocker, has anti-inflammatory effects on ICH by inhibiting the activation of the NLRP3 inflammasome. Sprague-Dawley rats were divided into five groups: sham, vehicle, low-dose (0.5 mg/kg) and regular-doses (1.0 and 3.0 mg/kg) fimasartan. These rats were treated for 30 days before the induction of collagenase-induced ICH and continuously 3 days after surgery. The mean blood pressure (BP) in the low-dose fimasartan group was not significantly different from that of control, and BP in the regular-dose groups was decreased in a dose-dependent manner. Pretreatment with low-dose fimasartan attenuated ICH-induced edema and improved neurological functions. Activation of the NLRP3/ASC/caspase-1 and the NF-κB pathways after ICH was markedly reduced by low-dose fimasartan. The double immunofluorescence staining of brain cells showed a significant decrease in the co-localization of NLRP3 with Iba1 (microglia marker) positive cells by fimasartan treatment. Cultured microglia cells stimulated by hemolysate demonstrated significant activation of the inflammasome, which was reduced by fimasartan. Pretreatment with a low-dose fimasartan alleviated brain damage after acute ICH by inhibiting the NLRP3 inflammasome without lowering MBP. Our study suggests pre-stroke administration of fimasartan could potentially attenuate ICH-induced secondary brain injury by targeting the inflammasome.

Original languageEnglish
Pages (from-to)22-32
Number of pages11
JournalExperimental Neurology
Volume310
DOIs
Publication statusPublished - 2018 Dec 1

Fingerprint

Inflammasomes
Cerebral Hemorrhage
Brain Injuries
Caspase 1
Microglia
Stroke
fimasartan
Angiotensin Receptor Antagonists
Brain
Collagenases
Ambulatory Surgical Procedures
Hypotension
Fluorescent Antibody Technique
Sprague Dawley Rats
Cultured Cells
Edema
Anti-Inflammatory Agents
Nucleotides
Apoptosis
Staining and Labeling

Keywords

  • Brain injury
  • Intracerebral hemorrhage
  • NLRP3 inflammasome
  • Stroke

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

Cite this

Pretreatment with low-dose fimasartan ameliorates NLRP3 inflammasome-mediated neuroinflammation and brain injury after intracerebral hemorrhage. / Yang, Xiuli; Sun, Jing; Kim, Tae Jung; Kim, Young Ju; Ko, Sang Bae; Kim, Chi Kyung; Jia, Xiaofeng; Yoon, Byung Woo.

In: Experimental Neurology, Vol. 310, 01.12.2018, p. 22-32.

Research output: Contribution to journalArticle

Yang, Xiuli ; Sun, Jing ; Kim, Tae Jung ; Kim, Young Ju ; Ko, Sang Bae ; Kim, Chi Kyung ; Jia, Xiaofeng ; Yoon, Byung Woo. / Pretreatment with low-dose fimasartan ameliorates NLRP3 inflammasome-mediated neuroinflammation and brain injury after intracerebral hemorrhage. In: Experimental Neurology. 2018 ; Vol. 310. pp. 22-32.
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