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) was associated with the pathophysiology of nHIE. In this study, we investigated morphological change and microglial activation under the nHIE condition and LOX-1 treatment. We assessed microglial activity and proliferation with a novel morphological methods, immunostaining and qPCR in the rat brains of both nHIE model and anti-LOX-1 treatment. We calculated the circumference ratio, the long-diameter ratio, the cell area ratio and the roundness of microglia. We evaluated the correlation of the morphological metrics and microglial activation in nHIE model and anti-LOX-1 treated brains. LOX-1 was expressed in activated ameboid and round microglia in nHIE model rat brain. As the evaluation of microglial activation, the novel morphological metrics correlated with all scales of the nHIE damaged and treated brains. The circumference ratio and long-diameter ratio had a positive correlation. On the contrary, the cell area ratio and roundness had a negative correlation. Anti-LOX-1 treatment attenuated morphologically 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 that anti-LOX-1 treatment attenuates brain injury by suppressing microglial activation.Copyright © 2021. Published by Elsevier Inc.
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