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

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, VEGF, and VEGFR2 were unchanged on day 28. We conclude that 20-HETE is involved in ICH-induced brain damage. Inhibition of 20-HETE synthesis may provide a viable means to mitigate ICH injury without inhibition of angiogenesis.

Ultrastructural Characteristics of Neuronal Death and White Matter Injury in Mouse Brain Tissues After Intracerebral Hemorrhage: Coexistence of Ferroptosis, Autophagy, and Necrosis

“…A total of 24 animals were used in this study. Animals and slice cultures for each group were randomized with the website www.randomization.com ( 32 , 33 ). This study was carried out in accordance with the recommendations of ARRIVE guidelines.…”

Cerebroprotection by salvianolic acid B after experimental subarachnoid hemorrhage occurs via Nrf2- and SIRT1-dependent pathways

“…Primary cortical neurons were prepared from the pups of pregnant C57BL/6 mice at 15–18 days’ gestation. The website Randomization.com (http://www.randomization.com) was used to assign animals into different study groups [25,33]. …”

“…In the first set of experiments, 159 rats (180 rats were used, 21 rats died) were randomly [33] divided into the following groups: sham + vehicle, sham + 20 mg/kg SalB, SAH + vehicle, SAH + 10 mg/kg SalB, SAH + 20 mg/kg SalB, and SAH + 40 mg/kg SalB. Rats were killed at 24 and 72 h after SAH.…”

“…In brief, brain sections were stained with H&E or Cresyl violet solution according to standard procedures [33,44,48–50], and then mounted onto microscope slides with Permount (Thermo Fisher Scientific). Staining was visualized under a light microscope.…”

Danhong Injection Protects Hemorrhagic Brain by Increasing Peroxiredoxin 1 in Aged Rats

“…d) was chosen for the present study. These animals were randomly divided into three groups (Han et al, 2019), as shown in Figure 1: (1) sham-operated (sham) group (n = 36), (2) ICH + vehicle group (n = 36), and (3) ICH + DHI group (n = 36). Animals in the ICH + DHI group were intraperitoneally administered with DHI on days 1, 3, and 7 after ICH (n = 12).…”