Wnt5a-Flt1 activation contributes to preterm altered cerebral angiogenesis after prenatal inflammation
Objective: Intraventricular hemorrhage (IVH) causes morbidity and mortality in preterm infants and prenatal exposure to inflammation contributes to brain injury. Moreover, prenatal exposure to severe inflammation increases the risk of IVH in preterm neonates. The current study investigated whether i...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Pediatrics and Neonatology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1875957223000347 |
| _version_ | 1797672089706037248 |
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| author | Han Jiangxue Yang Liling Xu Fang Yang Shumei Liu Gengying Ren Xuejun Yao Yao Nie Chuan Yang Jie Ren Zhuxiao |
| author_facet | Han Jiangxue Yang Liling Xu Fang Yang Shumei Liu Gengying Ren Xuejun Yao Yao Nie Chuan Yang Jie Ren Zhuxiao |
| author_sort | Han Jiangxue |
| collection | DOAJ |
| description | Objective: Intraventricular hemorrhage (IVH) causes morbidity and mortality in preterm infants and prenatal exposure to inflammation contributes to brain injury. Moreover, prenatal exposure to severe inflammation increases the risk of IVH in preterm neonates. The current study investigated whether intrauterine exposure to inflammation affects cerebral angiogenesis and its underlying mechanisms. Methods: Wnt5a, flt1, and vascular endothelial growth factor (VEGF)-A levels in cord blood serum (stored in a bio-bank) of the enrolled patients were measured via enzyme-linked immunosorbent assay. A preterm prenatal inflammation exposure model was established in rats by intraperitoneal injection intraperitoneally during pregnancy. Angiogenesis of cerebral tissue was analyzed using immunohistochemistry. Wnt5a, flt1, and VEGF-A expression levels were measured via immunohistochemistry, immunofluorescence, or western blotting. The correlation between Wnt5a and flt1 expression and the cerebral vessel area was also analyzed. Results: The Wnt5a and flt1 levels in the cord blood serum were significantly higher in the amnionitis group than in the non-amnionitis group. The VEGF-A level in the cord blood serum was significantly lower in the amnionitis group. In the rat model, preterm rats in the prenatal inflammation group exhibited increased microglial cell infiltration and decreased vessel area and diameter in the cerebral tissue compared to the control group. Wnt5a was located in microglial cells, and Wnt5a and flt1 expression in brain tissue significantly increased after prenatal lipopolysaccharide (LPS) exposure. VEGF-A expression declined after prenatal LPS exposure. The cerebral vessel area was negatively correlated with Wnt5a and flt1 expression. Conclusion: Disordered cerebral angiogenesis is associated with increased Wnt5a-Flt1 activation in microglial cells after exposure to intrauterine inflammation. |
| first_indexed | 2024-03-11T21:25:01Z |
| format | Article |
| id | doaj.art-875d9db5eb8a48a490227d31e8f02110 |
| institution | Directory Open Access Journal |
| issn | 1875-9572 |
| language | English |
| last_indexed | 2024-03-11T21:25:01Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pediatrics and Neonatology |
| spelling | doaj.art-875d9db5eb8a48a490227d31e8f021102023-09-28T05:25:11ZengElsevierPediatrics and Neonatology1875-95722023-09-01645528537Wnt5a-Flt1 activation contributes to preterm altered cerebral angiogenesis after prenatal inflammationHan Jiangxue0Yang Liling1Xu Fang2Yang Shumei3Liu Gengying4Ren Xuejun5Yao Yao6Nie Chuan7Yang Jie8Ren Zhuxiao9Department of Neonatology, Guangdong Key Clinical Specialty, Guangdong Women and Children Hospital, Guangzhou, ChinaDepartment of Neonatology, Guangdong Key Clinical Specialty, Guangdong Women and Children Hospital, Guangzhou, ChinaDepartment of Neonatology, Guangdong Key Clinical Specialty, Guangdong Women and Children Hospital, Guangzhou, ChinaDepartment of Neonatology, Guangdong Key Clinical Specialty, Guangdong Women and Children Hospital, Guangzhou, ChinaDepartment of Neonatology, Guangdong Key Clinical Specialty, Guangdong Women and Children Hospital, Guangzhou, ChinaDongguan Maternal and Children Hospital, Dong Guan, Guangdong, ChinaKey Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 190 Kaiyuan Avenue, Science Park, Guangzhou, Guangdong, ChinaDepartment of Neonatology, Guangdong Key Clinical Specialty, Guangdong Women and Children Hospital, Guangzhou, ChinaDepartment of Neonatology, Nanfang Hospital, Southern Medical University, China; Corresponding author.Department of Neonatology, Guangdong Key Clinical Specialty, Guangdong Women and Children Hospital, Guangzhou, China; Corresponding author. Guangdong Women and Children Hospital, 521 Xingnan Avenue, Guangzhou, Guangdong, 511442, China.Objective: Intraventricular hemorrhage (IVH) causes morbidity and mortality in preterm infants and prenatal exposure to inflammation contributes to brain injury. Moreover, prenatal exposure to severe inflammation increases the risk of IVH in preterm neonates. The current study investigated whether intrauterine exposure to inflammation affects cerebral angiogenesis and its underlying mechanisms. Methods: Wnt5a, flt1, and vascular endothelial growth factor (VEGF)-A levels in cord blood serum (stored in a bio-bank) of the enrolled patients were measured via enzyme-linked immunosorbent assay. A preterm prenatal inflammation exposure model was established in rats by intraperitoneal injection intraperitoneally during pregnancy. Angiogenesis of cerebral tissue was analyzed using immunohistochemistry. Wnt5a, flt1, and VEGF-A expression levels were measured via immunohistochemistry, immunofluorescence, or western blotting. The correlation between Wnt5a and flt1 expression and the cerebral vessel area was also analyzed. Results: The Wnt5a and flt1 levels in the cord blood serum were significantly higher in the amnionitis group than in the non-amnionitis group. The VEGF-A level in the cord blood serum was significantly lower in the amnionitis group. In the rat model, preterm rats in the prenatal inflammation group exhibited increased microglial cell infiltration and decreased vessel area and diameter in the cerebral tissue compared to the control group. Wnt5a was located in microglial cells, and Wnt5a and flt1 expression in brain tissue significantly increased after prenatal lipopolysaccharide (LPS) exposure. VEGF-A expression declined after prenatal LPS exposure. The cerebral vessel area was negatively correlated with Wnt5a and flt1 expression. Conclusion: Disordered cerebral angiogenesis is associated with increased Wnt5a-Flt1 activation in microglial cells after exposure to intrauterine inflammation.http://www.sciencedirect.com/science/article/pii/S1875957223000347cerebral angiogenesisprenatalinflammationpretermwnt5a-Flt1 |
| spellingShingle | Han Jiangxue Yang Liling Xu Fang Yang Shumei Liu Gengying Ren Xuejun Yao Yao Nie Chuan Yang Jie Ren Zhuxiao Wnt5a-Flt1 activation contributes to preterm altered cerebral angiogenesis after prenatal inflammation Pediatrics and Neonatology cerebral angiogenesis prenatalinflammation preterm wnt5a-Flt1 |
| title | Wnt5a-Flt1 activation contributes to preterm altered cerebral angiogenesis after prenatal inflammation |
| title_full | Wnt5a-Flt1 activation contributes to preterm altered cerebral angiogenesis after prenatal inflammation |
| title_fullStr | Wnt5a-Flt1 activation contributes to preterm altered cerebral angiogenesis after prenatal inflammation |
| title_full_unstemmed | Wnt5a-Flt1 activation contributes to preterm altered cerebral angiogenesis after prenatal inflammation |
| title_short | Wnt5a-Flt1 activation contributes to preterm altered cerebral angiogenesis after prenatal inflammation |
| title_sort | wnt5a flt1 activation contributes to preterm altered cerebral angiogenesis after prenatal inflammation |
| topic | cerebral angiogenesis prenatalinflammation preterm wnt5a-Flt1 |
| url | http://www.sciencedirect.com/science/article/pii/S1875957223000347 |
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