{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T16:22:26Z","timestamp":1779380546833,"version":"3.53.1"},"reference-count":56,"publisher":"BMJ","issue":"4","license":[{"start":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T00:00:00Z","timestamp":1754265600000},"content-version":"unspecified","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Neonatology Research, Education, Training Fund P1679 of the Loma Linda University, Department of Pediatrics.","award":["P1679"],"award-info":[{"award-number":["P1679"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["World Jnl Ped Surgery"],"accepted":{"date-parts":[[2025,6,19]]},"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Necrotizing enterocolitis (NEC) is associated with increased neurodevelopmental impairment. Gut-brain interactions through the brainstem may be central to NEC-related microglia-driven neuroinflammation. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) has intestinal protective properties and is a potential therapy for NEC. The aim of this study is to test the hypothesis that HB-EGF in pregnant rats reduces both NEC incidence and proinflammatory changes in the brainstem microglia of newborn rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We compared four experimental groups, HB-EGF\n                      <jats:sup>+<\/jats:sup>\n                      \/NEC\n                      <jats:sup>\u2013<\/jats:sup>\n                      , HB-EGF\n                      <jats:sup>\u2013<\/jats:sup>\n                      \/NEC\n                      <jats:sup>\u2013<\/jats:sup>\n                      , HB-EGF\n                      <jats:sup>+<\/jats:sup>\n                      \/NEC\n                      <jats:sup>+<\/jats:sup>\n                      and HB-EGF\n                      <jats:sup>\u2013<\/jats:sup>\n                      \/NEC\n                      <jats:sup>+<\/jats:sup>\n                      , depending on whether HB-EGF was given prenatally, and whether the newborn rats underwent the NEC induction protocol. We stained brainstem microglia and performed fractal analyses to provide objective measures of morphological changes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      NEC incidence was lower in the HB-EGF\n                      <jats:sup>+<\/jats:sup>\n                      \/NEC\n                      <jats:sup>+<\/jats:sup>\n                      group (\n                      <jats:italic>n<\/jats:italic>\n                      =64,\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.005) than in the HB-EGF\n                      <jats:sup>\u2013<\/jats:sup>\n                      \/NEC\n                      <jats:sup>+<\/jats:sup>\n                      group. Brainstem microglia of breastfed rats had a larger cell area, perimeter, roughness, and less circularity compared with smaller, denser, compact cells in the NEC\n                      <jats:sup>+<\/jats:sup>\n                      pups (\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.0001,\n                      <jats:italic>n<\/jats:italic>\n                      =320 cells). HB-EGF\n                      <jats:sup>+<\/jats:sup>\n                      \/NEC\n                      <jats:sup>+<\/jats:sup>\n                      and HB-EGF\n                      <jats:sup>\u2013<\/jats:sup>\n                      \/NEC\n                      <jats:sup>+<\/jats:sup>\n                      pups had similar-appearing microglia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Prenatal HB-EGF treatment reduces NEC incidence in neonatal rats. NEC-related proinflammatory changes are seen in microglial cells present in crucial centers controlling the gut-brain pathway. HB-EGF has a growth-promoting effect on healthy microglia in the offspring but does not avert microglial activation in the brainstem of newborn rats with NEC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/wjps-2025-001049","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T18:25:46Z","timestamp":1754418346000},"page":"e001049","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Brainstem microglial cell morphology in neonatal rats with necrotizing enterocolitis and the effects of prenatal heparin-binding epidermal growth factor-like growth factor"],"prefix":"10.1136","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4298-6421","authenticated-orcid":false,"given":"Vonita","family":"Chawla","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yomara 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