Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1-Related Microglial Activation in Neonatal Hypoxic-Ischemic Encephalopathy : Morphologic Consideration

Copyright © 2021 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved..

Neonatal hypoxic-ischemic encephalopathy (nHIE) is a major neonatal brain injury. Despite therapeutic hypothermia, mortality and sequelae remain severe. The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is associated with the pathophysiology of nHIE. In this study, morphologic change and microglial activation under the nHIE condition and LOX-1 treatment were investigated. The microglial activity and proliferation were assessed with a novel morphologic method, immunostaining, and quantitative PCR in the rat brains of both nHIE model and anti-LOX-1 treatment. Circumference ratio, the long diameter ratio, the cell area ratio, and the roundness of microglia were calculated. The correlation of the morphologic metrics and microglial activation in nHIE model and anti-LOX-1 treated brains was evaluated. LOX-1 was expressed in activated ameboid and round microglia in the nHIE model rat brain. In the evaluation of microglial activation, the novel morphologic metrics correlated with all scales of the nHIE-damaged and treated brains. While the circumference and long diameter ratios had a positive correlation, the cell area ratio and roundness had a negative correlation. Anti-LOX-1 treatment attenuated morphologic microglial activation and proliferation, and suppressed the subsequent production of inflammatory mediators by microglia. In human nHIE, round microglia and endothelial cells expressed LOX-1. The results indicate that LOX-1 regulates microglial activation in nHIE and anti-LOX-1 treatment attenuates brain injury by suppressing microglial activation.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:191

Enthalten in:

The American journal of pathology - 191(2021), 7 vom: 27. Juli, Seite 1303-1313

Sprache:

Englisch

Beteiligte Personen:

Akamatsu, Tomohisa [VerfasserIn]
Sugiyama, Takehiro [VerfasserIn]
Oshima, Takuya [VerfasserIn]
Aoki, Yoshinori [VerfasserIn]
Mizukami, Ayumi [VerfasserIn]
Goishi, Keiji [VerfasserIn]
Shichino, Hiroyuki [VerfasserIn]
Kato, Norihiro [VerfasserIn]
Takahashi, Naoto [VerfasserIn]
Goto, Yu-Ichi [VerfasserIn]
Oka, Akira [VerfasserIn]
Itoh, Masayuki [VerfasserIn]

Links:

Volltext

Themen:

Journal Article
Research Support, Non-U.S. Gov't
Scavenger Receptors, Class E

Anmerkungen:

Date Completed 26.07.2021

Date Revised 26.07.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.ajpath.2021.04.009

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM325158916