20-HETE synthesis inhibition promotes cerebral protection after intracerebral hemorrhage without inhibiting angiogenesis

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
Xiaoning HanJian Wang

Abstract

20-HETE, an arachidonic acid metabolite synthesized by cytochrome P450 4A, plays an important role in acute brain damage from ischemic stroke or subarachnoid hemorrhage. We tested the hypothesis that 20-HETE inhibition has a protective effect after intracerebral hemorrhage (ICH) and then investigated its effect on angiogenesis. We exposed hippocampal slice cultures to hemoglobin and induced ICH in mouse brains by intrastriatal collagenase injection to investigate the protective effect of 20-HETE synthesis inhibitor N-hydroxy-N'-(4-n-butyl-2-methylphenyl)-formamidine (HET0016). Hemoglobin-induced neuronal death was assessed by propidium iodide after 18 h in vitro. Lesion volume, neurologic deficits, cell death, reactive oxygen species (ROS), neuroinflammation, and angiogenesis were evaluated at different time points after ICH. In cultured mouse hippocampal slices, HET0016 attenuated hemoglobin-induced neuronal death and decreased levels of proinflammatory cytokines and ROS. In vivo, HET0016 reduced brain lesion volume and neurologic deficits, and decreased neuronal death, ROS production, gelatinolytic activity, and the inflammatory response at three days after ICH. However, HET0016 did not inhibit angiogenesis, as levels of CD31...Continue Reading

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Citations

Jul 27, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Xiangsheng ZhangJian Wang
Apr 16, 2020·Frontiers in Pharmacology·Shang WangHong Lu
Sep 14, 2019·International Journal of Molecular Sciences·Shashank ShekharFan Fan
Oct 20, 2020·Frontiers in Neuroscience·Jun-Jie YuanQing-Wu Yang
Apr 20, 2021·Journal of Neuropathology and Experimental Neurology·Ze ZhangHe Wu
Jul 10, 2021·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Honglei RenJian Wang

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Datasets Mentioned

BETA
MCA1957

Methods Mentioned

BETA
electrophoresis
protein assay
ELISA
PCR
carbonylation

Software Mentioned

Image J

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