World J Pediatr Surg. 2025 Aug 5;8(4):e001049. doi: 10.1136/wjps-2025-001049. eCollection 2025.
ABSTRACT
BACKGROUND: 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.
METHODS: We compared four experimental groups, HB-EGF+/NEC–, HB-EGF–/NEC–, HB-EGF+/NEC+ and HB-EGF–/NEC+, 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.
RESULTS: NEC incidence was lower in the HB-EGF+/NEC+ group (n=64, p<0.005) than in the HB-EGF–/NEC+ 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+ pups (p<0.0001, n=320 cells). HB-EGF+/NEC+ and HB-EGF–/NEC+ pups had similar-appearing microglia.
CONCLUSIONS: 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.
PMID:40799955 | PMC:PMC12336531 | DOI:10.1136/wjps-2025-001049
