{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T03:19:43Z","timestamp":1778642383476,"version":"3.51.4"},"reference-count":89,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Neonatology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Germany"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neonatal hyperoxia induces oxidative and inflammatory stress that disrupts cardiac maturation and contributes to long-term cardiovascular morbidity in individuals born preterm. Cannabidiol (CBD), a non-psychoactive phytocannabinoid with antioxidant and anti-inflammatory properties, has demonstrated protective effects in neonatal hyperoxic injury in other organs; however, its impact on the developing heart remains unclear. This study investigated whether CBD mitigates hyperoxia-induced cardiac injury in a neonatal mouse model. Newborn mice were exposed to 80% O2 for 48 h from postnatal day (P)5 to P7 and received vehicle, 10 mg\/kg CBD, or 30 mg\/kg CBD intraperitoneally, while controls remained in room air. Hearts were collected at P7 or after recovery until P14. Hyperoxia triggered oxidative stress (Nrf2), inflammation (IL1\u03b2, TNF\u03b1, IL6, CXCL1; p &lt; 0.05), and dysregulated apoptosis\/autophagy, leading to reduced cardiomyocyte proliferation (Ki67+ \u221250% at P14; p &lt; 0.01) and adverse remodeling (hypertrophy, fibrosis; p &lt; 0.01). CBD attenuated these responses and normalized autophagy (Atg5, Atg12; p &lt; 0.05). Notably, 10 mg\/kg CBD, but not 30 mg\/kg, preserved proliferative capacity and reduced wall thickness, suggesting a narrow therapeutic window, while both doses limited collagen deposition and apoptosis (Casp3, AIF; p &lt; 0.05). Several effects were sex-dependent, with males exhibiting more pronounced long-term structural and proliferative impairments and greater responsiveness to low-dose CBD. These findings identify CBD as a potential cardioprotective modulator of neonatal hyperoxia-induced injury and highlight the importance of dose- and sex-specific mechanisms in early cardiac maturation.<\/jats:p>","DOI":"10.3390\/ijms27010146","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T10:57:18Z","timestamp":1766487438000},"page":"146","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cannabidiol Protects the Neonatal Mouse Heart from Hyperoxia-Induced Injury"],"prefix":"10.3390","volume":"27","author":[{"given":"Teresa","family":"Hellberg","sequence":"first","affiliation":[{"name":"Department of Neonatology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8193-8970","authenticated-orcid":false,"given":"Thomas","family":"Schmitz","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9950-414X","authenticated-orcid":false,"given":"Christoph","family":"B\u00fchrer","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4030-7969","authenticated-orcid":false,"given":"Stefanie","family":"Endesfelder","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1001\/jamapediatrics.2024.1848","article-title":"Initial Oxygen Concentration for the Resuscitation of Infants Born at Less Than 32 Weeks\u2019 Gestation: A Systematic Review and Individual Participant Data Network Meta-Analysis","volume":"178","author":"Sotiropoulos","year":"2024","journal-title":"JAMA Pediatr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s10565-022-09773-7","article-title":"Oxygen toxicity: Cellular mechanisms in normobaric hyperoxia","volume":"39","author":"Alva","year":"2023","journal-title":"Cell Biol. 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