Enhancing 7-dehydrocholesterol suppresses brain ferroptosis and tissue injury after neonatal hypoxia-ischemia.

Autor: Genaro-Mattos TC; Munroe-Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha, NE, 68106, USA., Korade Z; Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE, 68198, USA.; Child Health Research Institute, Omaha, NE, 68198, USA., Sahar NE; Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE, 68198, USA.; Child Health Research Institute, Omaha, NE, 68198, USA., Angeli JPF; Rudolf Virchow Zentrum - Center for Integrative and Translational Bioimaging, University of Würzburg, Würzburg, Germany., Mirnics K; Munroe-Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha, NE, 68106, USA.; Child Health Research Institute, Omaha, NE, 68198, USA., Peeples ES; Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE, 68198, USA. epeeples@childrensnebraska.org.; Child Health Research Institute, Omaha, NE, 68198, USA. epeeples@childrensnebraska.org.; Department of Pediatrics, Children's Nebraska, Omaha, NE, 68114, USA. epeeples@childrensnebraska.org.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Apr 04; Vol. 14 (1), pp. 7924. Date of Electronic Publication: 2024 Apr 04.
DOI: 10.1038/s41598-024-58579-6
Abstrakt: Neonatal hypoxic-ischemic brain injury (HIBI) results in part from excess reactive oxygen species and iron-dependent lipid peroxidation (i.e. ferroptosis). The vitamin D precursor 7-dehydrocholesterol (7-DHC) may inhibit iron-dependent lipid peroxidation. Primary neurons underwent oxygen and glucose deprivation (OGD) injury and treatment with 7-DHC-elevating medications such as cariprazine (CAR) or vehicle. Postnatal day 9 mice underwent sham surgery or carotid artery ligation and hypoxia and received intraperitoneal CAR. In neurons, CAR administration resulted in significantly increased cell survival compared to vehicle controls, whether administered 48 h prior to or 30 min after OGD, and was associated with increased 7-DHC. In the mouse model, malondialdehyde and infarct area significantly increased after HIBI in the vehicle group, which were attenuated by post-treatment with CAR and were negatively correlated with tissue 7-DHC concentrations. Elevating 7-DHC concentrations with CAR was associated with improved cellular and tissue viability after hypoxic-ischemic injury, suggesting a novel therapeutic avenue.
(© 2024. The Author(s).)
Databáze: MEDLINE
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