{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T08:43:14Z","timestamp":1777624994377,"version":"3.51.4"},"reference-count":213,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T00:00:00Z","timestamp":1699315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Sickle cell anemia (SCA) is a genetic disease caused by the homozygosity of the HBB:c.20A&gt;T mutation, which results in the production of hemoglobin S (HbS). In hypoxic conditions, HbS suffers autoxidation and polymerizes inside red blood cells, altering their morphology into a sickle shape, with increased rigidity and fragility. This triggers complex pathophysiological mechanisms, including inflammation, cell adhesion, oxidative stress, and vaso-occlusion, along with metabolic alterations and endocrine complications. SCA is phenotypically heterogeneous due to the modulation of both environmental and genetic factors. Pediatric cerebrovascular disease (CVD), namely ischemic stroke and silent cerebral infarctions, is one of the most impactful manifestations. In this review, we highlight the role of oxidative stress in the pathophysiology of pediatric CVD. Since oxidative stress is an interdependent mechanism in vasculopathy, occurring alongside (or as result of) endothelial dysfunction, cell adhesion, inflammation, chronic hemolysis, ischemia-reperfusion injury, and vaso-occlusion, a brief overview of the main mechanisms involved is included. Moreover, the genetic modulation of CVD in SCA is discussed. The knowledge of the intricate network of altered mechanisms in SCA, and how it is affected by different genetic factors, is fundamental for the identification of potential therapeutic targets, drug development, and patient-specific treatment alternatives.<\/jats:p>","DOI":"10.3390\/antiox12111977","type":"journal-article","created":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T11:23:39Z","timestamp":1699356219000},"page":"1977","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["From Stress to Sick(le) and Back Again\u2013Oxidative\/Antioxidant Mechanisms, Genetic Modulation, and Cerebrovascular Disease in Children with Sickle Cell Anemia"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3575-1261","authenticated-orcid":false,"given":"Marisa","family":"Silva","sequence":"first","affiliation":[{"name":"Departamento de Gen\u00e9tica Humana, Instituto Nacional de Sa\u00fade Doutor Ricardo Jorge (INSA), Av. Padre Cruz, 1649-016 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6269-4867","authenticated-orcid":false,"given":"Paula","family":"Faustino","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica Humana, Instituto Nacional de Sa\u00fade Doutor Ricardo Jorge (INSA), Av. Padre Cruz, 1649-016 Lisboa, Portugal"},{"name":"Grupo Ecogen\u00e9tica e Sa\u00fade Humana, Instituto de Sa\u00fade Ambiental (ISAMB), Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal"},{"name":"Laborat\u00f3rio Associado TERRA, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e80","DOI":"10.1016\/S2214-109X(13)70150-5","article-title":"Global Migration and the Changing Distribution of Sickle Haemoglobin: A Quantitative Study of Temporal Trends between 1960 and 2000","volume":"2","author":"Piel","year":"2014","journal-title":"Lancet Glob. Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1056\/NEJMra1510865","article-title":"Sickle Cell Disease","volume":"376","author":"Piel","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"H1460","DOI":"10.1152\/ajpheart.2000.279.4.H1460","article-title":"Influence of Erythrocyte Aggregation on Leukocyte Margination in Postcapillary Expansions: A Lattice Boltzmann Analysis","volume":"279","author":"Pearson","year":"2000","journal-title":"Am. J. 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