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However, the impact of hypoxia-ischemia in certain brain regions and its association with genetic sex remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using the piglet model of neonatal brain injury, fifteen piglets (8 females and 7 males) were subjected to a global cerebral hypoxic-ischemic insult. After 48\u2009h, total cell death and the number of necrotic, apoptotic and cleaved-caspase-3 positive cells was quantified in five brain regions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Male piglets exposed to hypoxia-ischemia were more vulnerable than females (total cell death\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01), also showing a region-specific response to brain injury depending on sex, with males being more affected in both deep gray (caudate\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01; THAL\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001) and white (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01) matter. Despite necrosis was the primary form of cell death for both sexes, the pattern of cell death differed: while male piglets showed more necrosis (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001), apoptosis (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001) and caspase-3 activation (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001) were higher in females.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our results suggest that male piglets were globally and regionally more vulnerable than females after HI; further, both the pattern of cell death and the apoptotic molecular mechanisms were sexually dimorphic.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Impact<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Clinical data suggest that females might be more resistant to perinatal asphyxia than male newborns. The impact of hypoxia-ischemia in certain brain regions and the association of cell death patterns with sex remain unclear.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Hypoxic-ischemic male piglets were more vulnerable than females, showing also increased regional vulnerability in both deep gray and white matter areas.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Although necrosis was the primary form of cell death for both sexes, male piglets showed more necrosis, whereas apoptosis and caspase-3 activation were higher in females.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Neonatal brain injury and therapeutic responses may be sex-dependent due to differences in cell death patterns and molecular mechanisms.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41390-025-04046-5","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T11:45:16Z","timestamp":1744803916000},"page":"1120-1127","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Sex dimorphism in brain cell death after hypoxia-ischemia in newborn piglets"],"prefix":"10.1038","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9874-2947","authenticated-orcid":false,"given":"Daniel","family":"Alonso-Alconada","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Chillida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Catalan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Gressens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola J.","family":"Robertson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,16]]},"reference":[{"key":"4046_CR1","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1093\/cercor\/11.6.490","volume":"11","author":"JM Goldstein","year":"2001","unstructured":"Goldstein, J. 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