{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T01:44:02Z","timestamp":1760233442672,"version":"build-2065373602"},"reference-count":92,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T00:00:00Z","timestamp":1610409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HD-054920","HD-31266","HL-54120","HL-64867","NS-082184","NS-076945"],"award-info":[{"award-number":["HD-054920","HD-31266","HL-54120","HL-64867","NS-082184","NS-076945"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The present study explored the hypothesis that an adverse intrauterine environment caused by maternal undernutrition (MUN) acted through corticosteroid-dependent and -independent mechanisms to program lasting functional changes in the neonatal cerebrovasculature and vulnerability to mild hypoxic-ischemic (HI) injury. From day 10 of gestation until term, MUN and MUN-metyrapone (MUN-MET) group rats consumed a diet restricted to 50% of calories consumed by a pair-fed control; and on gestational day 11 through term, MUN-MET groups received drinking water containing MET (0.5 mg\/mL), a corticosteroid synthesis inhibitor. P9\/P10 pups underwent unilateral carotid ligation followed 24 h later by 1.5 h exposure to 8% oxygen (HI treatment). An ELISA quantified MUN-, MET-, and HI-induced changes in circulating levels of corticosterone. In P11\/P12 pups, MUN programming promoted contractile differentiation in cerebrovascular smooth muscle as determined by confocal microscopy, modulated calcium-dependent contractility as revealed by cerebral artery myography, enhanced vasogenic edema formation as indicated by T2 MRI, and worsened neurobehavior MUN unmasked HI-induced improvements in open-field locomotion and in edema resolution, alterations in calcium-dependent contractility and promotion of contractile differentiation. Overall, MUN imposed multiple interdependent effects on cerebrovascular smooth muscle differentiation, contractility, edema formation, flow-metabolism coupling and neurobehavior through pathways that both required, and were independent of, gestational corticosteroids. In light of growing global patterns of food insecurity, the present study emphasizes that infants born from undernourished mothers may experience greater risk for developing neonatal cerebral edema and sensorimotor impairments possibly through programmed changes in neonatal cerebrovascular function.<\/jats:p>","DOI":"10.3390\/ijms22020680","type":"journal-article","created":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T14:28:53Z","timestamp":1610461733000},"page":"680","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Maternal Undernutrition Modulates Neonatal Rat Cerebrovascular Structure, Function, and Vulnerability to Mild Hypoxic-Ischemic Injury via Corticosteroid-Dependent and -Independent Mechanisms"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8326-4110","authenticated-orcid":false,"given":"Patsy Naomi","family":"Franco","sequence":"first","affiliation":[{"name":"Center for Perinatal Biology, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lara M.","family":"Durrant","sequence":"additional","affiliation":[{"name":"Center for Perinatal Biology, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Coleen","family":"Doan","sequence":"additional","affiliation":[{"name":"Center for Perinatal Biology, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Desirelys","family":"Carreon","sequence":"additional","affiliation":[{"name":"Center for Perinatal Biology, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandra","family":"Beltran","sequence":"additional","affiliation":[{"name":"Center for Perinatal Biology, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9458-055X","authenticated-orcid":false,"given":"Amandine","family":"Jullienne","sequence":"additional","affiliation":[{"name":"Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0081-6950","authenticated-orcid":false,"given":"Andre","family":"Obenaus","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California, Irvine, CA 92697, USA"},{"name":"Preclinical and Translational Imaging Center, University of California, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William J.","family":"Pearce","sequence":"additional","affiliation":[{"name":"Center for Perinatal Biology, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,12]]},"reference":[{"key":"ref_1","unstructured":"Coleman-Jensen, A.R., Pabbitt, M.P., Gregory, C.A., and Singh, A. (2020). Household Food Security in the United States in 2019. ERR-275, United States Department of Agriculture, Economic Research Service."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e13036","DOI":"10.1111\/mcn.13036","article-title":"COVID-19 and maternal and child food and nutrition insecurity: A complex syndemic","volume":"16","author":"Cunningham","year":"2020","journal-title":"Matern. Child Nutr."},{"key":"ref_3","first-page":"213","article-title":"Early famine exposure and adult disease risk based on a 10-year prospective study of Chinese adults","volume":"106","author":"Meng","year":"2020","journal-title":"Heart"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"T135","DOI":"10.1530\/JOE-18-0683","article-title":"Epidemiological evidence for the developmental origins of health and disease: Effects of prenatal undernutrition in humans","volume":"242","author":"Roseboom","year":"2019","journal-title":"J. Endocrinol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1136\/bmj.311.6998.171","article-title":"Fetal origins of coronary heart disease","volume":"311","author":"Barker","year":"1995","journal-title":"BMJ"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1093\/nutrit\/nux053","article-title":"Developmental origins of health and disease: Current knowledge and potential mechanisms","volume":"75","author":"Hoffman","year":"2017","journal-title":"Nutr. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1055\/s-0029-1237427","article-title":"Developmental origins of health and disease: Environmental exposures","volume":"27","author":"Swanson","year":"2009","journal-title":"Semin. Reprod. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1038\/ncpendmet0515","article-title":"Mechanisms of disease: Glucocorticoids, their placental metabolism and fetal \u2018programming\u2019 of adult pathophysiology","volume":"3","author":"Seckl","year":"2007","journal-title":"Nat. Clin. Pract. Endocrinol. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1016\/S0140-6736(18)30312-X","article-title":"Origins of lifetime health around the time of conception: Causes and consequences","volume":"391","author":"Fleming","year":"2018","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1002\/bdr2.1142","article-title":"Hypoxia: From Placental Development to Fetal Programming","volume":"109","author":"Fajersztajn","year":"2017","journal-title":"Birth Defects Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1002\/bdra.20277","article-title":"Review: Hyperthermia and fever during pregnancy","volume":"76","author":"Edwards","year":"2006","journal-title":"Birth Defects Res. Part A Clin. Mol. Teratol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"213","DOI":"10.2217\/epi-2017-0008","article-title":"Air pollution and in utero programming of poor fetal growth","volume":"9","author":"Burris","year":"2017","journal-title":"Epigenomics"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1002\/bdr2.1435","article-title":"Maternal hyperglycemia and fetal cardiac development: Clinical impact and underlying mechanisms","volume":"110","author":"Basu","year":"2018","journal-title":"Birth Defects Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.yfrne.2012.08.006","article-title":"The immune system and developmental programming of brain and behavior","volume":"33","author":"Bilbo","year":"2012","journal-title":"Front. Neuroendocrinol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.ejogrb.2019.02.005","article-title":"Fetal growth and maternal alcohol consumption during early pregnancy","volume":"236","author":"Reynolds","year":"2019","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1055\/s-0035-1570029","article-title":"Predisposing Factors to Abnormal First Trimester Placentation and the Impact on Fetal Outcomes","volume":"34","author":"Kroener","year":"2016","journal-title":"Semin. Reprod. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1152\/physrev.00029.2015","article-title":"Placental Origins of Chronic Disease","volume":"96","author":"Burton","year":"2016","journal-title":"Physiol. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"841","DOI":"10.2174\/1567205014666170425112331","article-title":"Nutritional Deficiency in Early Life Facilitates Aging-Associated Cognitive Decline","volume":"14","author":"Kang","year":"2017","journal-title":"Curr. Alzheimer Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e1996","DOI":"10.1212\/WNL.0000000000009407","article-title":"In utero exposure to the Great Chinese Famine and risk of intracerebral hemorrhage in midlife","volume":"94","author":"Li","year":"2020","journal-title":"Neurology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5791","DOI":"10.1113\/JP275030","article-title":"Role of fetal nutrient restriction and postnatal catch-up growth on structural and mechanical alterations of rat aorta","volume":"596","author":"Greenwald","year":"2018","journal-title":"J. Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"S869","DOI":"10.1016\/j.ajog.2017.12.012","article-title":"Long-term cardiovascular consequences of fetal growth restriction: Biology, clinical implications, and opportunities for prevention of adult disease","volume":"218","author":"Crispi","year":"2018","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1093\/jn\/137.4.1066","article-title":"Maternal nutrition, low nephron number, and hypertension in later life: Pathways of nutritional programming","volume":"137","author":"Bagby","year":"2007","journal-title":"J. Nutr."},{"key":"ref_23","first-page":"594738","article-title":"An evolutionary perspective of animal microRNAs and their targets","volume":"2009","author":"Shomron","year":"2009","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.psyneuen.2012.08.012","article-title":"Glucocorticoid excess and the developmental origins of disease: Two decades of testing the hypothesis\u20142012 Curt Richter Award Winner","volume":"38","author":"Reynolds","year":"2013","journal-title":"Psychoneuroendocrinology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1210\/js.2019-00158","article-title":"Glucocorticoid and Mineralocorticoid Receptors in the Brain: A Transcriptional Perspective","volume":"3","author":"Koning","year":"2019","journal-title":"J. Endocr. Soc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1210\/endo.142.5.8139","article-title":"Maternal undernutrition during late gestation induces fetal overexposure to glucocorticoids and intrauterine growth retardation, and disturbs the hypothalamo-pituitary adrenal axis in the newborn rat","volume":"142","author":"Lesage","year":"2001","journal-title":"Endocrinology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1177\/1933719113508819","article-title":"Excess maternal glucocorticoids in response to in utero undernutrition inhibit offspring angiogenesis","volume":"21","author":"Khorram","year":"2014","journal-title":"Reprod. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1124\/jpet.110.167148","article-title":"Pharmacodynamic and pharmacokinetic characterization of the aldosterone synthase inhibitor FAD286 in two rodent models of hyperaldosteronism: Comparison with the 11beta-hydroxylase inhibitor metyrapone","volume":"334","author":"Rigel","year":"2010","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1146\/annurev.pa.10.040170.001215","article-title":"Inhibitors of adrenal steroid biosynthesis","volume":"10","author":"Temple","year":"1970","journal-title":"Annu. Rev. Pharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"R85","DOI":"10.1152\/ajpregu.00435.2004","article-title":"Maternal low-protein diet in rat pregnancy programs blood pressure through sex-specific mechanisms","volume":"288","author":"McMullen","year":"2005","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.ajog.2007.01.020","article-title":"In utero undernutrition in rats induces increased vascular smooth muscle content in the offspring","volume":"196","author":"Khorram","year":"2007","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"C1090","DOI":"10.1152\/ajpcell.00408.2011","article-title":"Chronic hypoxia and VEGF differentially modulate abundance and organization of myosin heavy chain isoforms in fetal and adult ovine arteries","volume":"303","author":"Hubbell","year":"2012","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_33","first-page":"100","article-title":"Regulation and characteristics of vascular smooth muscle cell phenotypic diversity","volume":"15","author":"Rensen","year":"2007","journal-title":"Neth. Heart J. Mon. J. Neth. Soc. Cardiol. Neth. Heart Found."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"C493","DOI":"10.1152\/ajpcell.00131.2007","article-title":"Myosin II isoforms in smooth muscle: Heterogeneity and function","volume":"293","author":"Eddinger","year":"2007","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1152\/ajpregu.00145.2019","article-title":"Prenatal metyrapone treatment modulates neonatal cerebrovascular structure, function, and vulnerability to mild hypoxic-ischemic injury","volume":"318","author":"Franco","year":"2020","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"R401","DOI":"10.1152\/ajpregu.00436.2013","article-title":"Maternal food restriction modulates cerebrovascular structure and contractility in adult rat offspring: Effects of metyrapone","volume":"306","author":"Durrant","year":"2014","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.spen.2018.05.003","article-title":"Fetal Cerebrovascular Maturation: Effects of Hypoxia","volume":"28","author":"Pearce","year":"2018","journal-title":"Semin. Pediatr. Neurol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"H628","DOI":"10.1152\/ajpheart.00165.2007","article-title":"Transient middle cerebral artery occlusion causes different structural, mechanical, and myogenic alterations in normotensive and hypertensive rats","volume":"293","author":"Rojas","year":"2007","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1111\/j.1469-7793.2001.0141m.x","article-title":"Dietary restriction in pregnant rats causes gender-related hypertension and vascular dysfunction in offspring","volume":"530","author":"Ozaki","year":"2001","journal-title":"J. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1203\/01.PDR.0000065731.00639.02","article-title":"Dietary Protein Restriction in Pregnancy Induces Hypertension and Vascular Defects in Rat Male Offspring","volume":"54","author":"Brawley","year":"2003","journal-title":"Pediatric Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"789","DOI":"10.3174\/ajnr.A4183","article-title":"Computer-assisted volumetric measurement of core infarct volume in pediatric patients: Feasibility for clinical use and development of quantitative metrics for outcome prediction","volume":"36","author":"Filippi","year":"2015","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1038\/pr.2017.152","article-title":"Preventing harmful effects of epileptic seizures on cerebrovascular functions in newborn pigs: Does sex matter?","volume":"82","author":"Liu","year":"2017","journal-title":"Pediatr. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1002\/cbf.3209","article-title":"Myosin light chain kinase steady-state kinetics: Comparison of smooth muscle myosin II and nonmuscle myosin IIB as substrates","volume":"34","author":"Alcala","year":"2016","journal-title":"Cell Biochem. Funct."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.bcp.2018.02.012","article-title":"Evolving mechanisms of vascular smooth muscle contraction highlight key targets in vascular disease","volume":"153","author":"Liu","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1002\/jnr.23828","article-title":"Sex-dependent consequences of neonatal brain hypoxia-ischemia in the rat","volume":"95","author":"Netto","year":"2017","journal-title":"J. Neurosci. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.neulet.2008.10.014","article-title":"Fetal undernutrition induces overexpression of CRH mRNA and CRH protein in hypothalamus and increases CRH and corticosterone in plasma during postnatal life in the rat","volume":"448","author":"Nunez","year":"2008","journal-title":"Neurosci. Lett."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"328","DOI":"10.3109\/10253890.2015.1064890","article-title":"Early-life adversity programs emotional functions and the neuroendocrine stress system: The contribution of nutrition, metabolic hormones and epigenetic mechanisms","volume":"18","author":"Yam","year":"2015","journal-title":"Stress"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1093\/bja\/85.1.109","article-title":"The stress response to trauma and surgery","volume":"85","author":"Desborough","year":"2000","journal-title":"Br. J. Anaesth."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e12610","DOI":"10.1111\/jne.12610","article-title":"Maternal regulation of the infant\u2019s hypothalamic-pituitary-adrenal axis stress response: Seymour \u2018Gig\u2019 Levine\u2019s legacy to neuroendocrinology","volume":"30","author":"Suchecki","year":"2018","journal-title":"J. Neuroendocrinol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1079\/BJN19910015","article-title":"The effects of fasting on plasma corticosterone kinetics in rats","volume":"66","author":"Woodward","year":"1991","journal-title":"Br. J. Nutr."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1677\/joe.0.1750099","article-title":"Plasma binding proteins as mediators of corticosteroid action in vertebrates","volume":"175","author":"Breuner","year":"2002","journal-title":"J. Endocrinol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1111\/1440-1681.12125","article-title":"Direct contribution of vascular mineralocorticoid receptors to blood pressure regulation","volume":"40","author":"Barrett","year":"2013","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e11","DOI":"10.1017\/S1462399411001815","article-title":"Angiotensin II and the vascular phenotype in hypertension","volume":"13","author":"Savoia","year":"2011","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Guti\u00e9rrez-Arzapalo, P.Y., Rodr\u00edguez-Rodr\u00edguez, P., Ramiro-Cortijo, D., Gil-Ortega, M., Somoza, B., de Pablo, \u00c1.L.L., Gonz\u00e1lez, M.D.C., and Arribas, S.M. (2020). Fetal Undernutrition Induces Resistance Artery Remodeling and Stiffness in Male and Female Rats Independent of Hypertension. Biomedicines, 8.","DOI":"10.3390\/biomedicines8100424"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.ebiom.2018.11.054","article-title":"Mineralocorticoid receptor: A hidden culprit for hemodialysis vascular access dysfunction","volume":"39","author":"Chen","year":"2019","journal-title":"EBioMedicine"},{"key":"ref_56","unstructured":"Sorensen, D.W., Carreon, D., Williams, J.M., and Pearce, W.J. (2020). Hypoxic Modulation of Fetal Vascular MLCK Abundance, Localization, and Function. Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1097\/GRF.0b013e31829e5bc9","article-title":"Maturation and differentiation of the fetal vasculature","volume":"56","author":"Pearce","year":"2013","journal-title":"Clin. Obstet. Gynecol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1007\/s00424-008-0491-8","article-title":"The non-excitable smooth muscle: Calcium signaling and phenotypic switching during vascular disease","volume":"456","author":"House","year":"2008","journal-title":"Pflug. Arch. Eur. J. Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"C117","DOI":"10.1152\/ajpcell.00254.2014","article-title":"miR-29c induction contributes to downregulation of vascular extracellular matrix proteins by glucocorticoids","volume":"309","author":"Chuang","year":"2015","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1152\/physrev.00023.2003","article-title":"C2+ sensitivity of smooth muscle and nonmuscle myosin II: Modulated by G proteins, kinases, and myosin phosphatase","volume":"83","author":"Somlyo","year":"2003","journal-title":"Physiol. Rev."},{"key":"ref_61","first-page":"131","article-title":"Effect of Hypoproteic and High-Fat Diets on Hippocampal Blood-Brain Barrier Permeability and Oxidative Stress","volume":"5","author":"Guerrant","year":"2018","journal-title":"Front. Nutr."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.reprotox.2012.01.013","article-title":"Maternal undernutrition reduces P-glycoprotein in guinea pig placenta and developing brain in late gestation","volume":"33","author":"Soo","year":"2012","journal-title":"Reprod. Toxicol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"100796","DOI":"10.1016\/j.spen.2020.100796","article-title":"Neonatal Neuroimaging","volume":"33","author":"Miller","year":"2020","journal-title":"Semin. Pediatr. Neurol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Neuhaus, W., Schlundt, M., Fehrholz, M., Ehrke, A., Kunzmann, S., Liebner, S., Speer, C.P., and F\u00f6rster, C.Y. (2015). Multiple Antenatal Dexamethasone Treatment Alters Brain Vessel Differentiation in Newborn Mouse Pups. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0136221"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"R468","DOI":"10.1152\/ajpregu.2000.279.2.R468","article-title":"Exogenous and endogenous corticosteroids modulate blood-brain barrier development in the ovine fetus","volume":"279","author":"Stonestreet","year":"2000","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1007\/s00441-013-1762-z","article-title":"Glucocorticoids and endothelial cell barrier function","volume":"355","author":"Salvador","year":"2014","journal-title":"Cell Tissue Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1067\/mob.2002.121624","article-title":"Repeated doses of antenatal corticosteroids in animals: A systematic review","volume":"186","author":"Aghajafari","year":"2002","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.neuint.2003.11.010","article-title":"Nuclear magnetic resonance (NMR) measurement of the apparent diffusion coefficient (ADC) of tissue water and its relationship to cell volume changes in pathological states","volume":"45","author":"Sotak","year":"2004","journal-title":"Neurochem. Int."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1002\/nbm.1127","article-title":"MRI-measured water mobility increases in response to chemotherapy via multiple cell-death mechanisms","volume":"20","author":"Morse","year":"2007","journal-title":"NMR Biomed."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Feather-Schussler, D.N., and Ferguson, T.S. (2016). A Battery of Motor Tests in a Neonatal Mouse Model of Cerebral Palsy. J. Vis. Exp.","DOI":"10.3791\/53569-v"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Seibenhener, M.L., and Wooten, M.C. (2015). Use of the Open Field Maze to measure locomotor and anxiety-like behavior in mice. J. Vis. Exp.","DOI":"10.3791\/52434-v"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"634","DOI":"10.3389\/fphys.2019.00634","article-title":"Mild Neonatal Brain Hypoxia-Ischemia in Very Immature Rats Causes Long-Term Behavioral and Cerebellar Abnormalities at Adulthood","volume":"10","author":"Sanches","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1113\/jphysiol.2007.149229","article-title":"Low protein diet fed exclusively during mouse oocyte maturation leads to behavioural and cardiovascular abnormalities in offspring","volume":"586","author":"Watkins","year":"2008","journal-title":"J. Physiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.brainresbull.2010.06.005","article-title":"Effects of maternal food restriction on physical growth and neurobehavior in newborn Wistar rats","volume":"83","author":"Zhang","year":"2010","journal-title":"Brain Res. Bull."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.nbd.2012.03.021","article-title":"Role of the pituitary-adrenal axis in granulocyte-colony stimulating factor-induced neuroprotection against hypoxia-ischemia in neonatal rats","volume":"47","author":"Charles","year":"2012","journal-title":"Neurobiol. Dis."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2364","DOI":"10.1210\/endo.135.6.7988418","article-title":"Corticotropin-releasing hormone mediates the response to cold stress in the neonatal rat without compensatory enhancement of the peptide\u2019s gene expression","volume":"135","author":"Yi","year":"1994","journal-title":"Endocrinology"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/S0024-3205(98)00393-2","article-title":"Mechanisms involved in the cellular calcium homeostasis in vascular smooth muscle: Calcium pumps","volume":"64","author":"Marin","year":"1999","journal-title":"Life Sci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1161\/01.RES.0000216596.73005.3c","article-title":"Excitation-transcription coupling in arterial smooth muscle","volume":"98","author":"Wamhoff","year":"2006","journal-title":"Circ. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1161\/01.STR.32.4.958","article-title":"Correlation of cerebral hypoxic-ischemic T2 changes with tissue alterations in water content and protein extravasation","volume":"32","author":"Qiao","year":"2001","journal-title":"Stroke"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1161\/01.STR.10.5.542","article-title":"Brain edema during ischemia and after restoration of blood flow. Measurement of water, sodium, potassium content and plasma protein permeability","volume":"10","author":"Ito","year":"1979","journal-title":"Stroke"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1161\/01.STR.28.2.419","article-title":"Spreading of vasogenic edema and cytotoxic edema assessed by quantitative diffusion and T2 magnetic resonance imaging","volume":"28","author":"Loubinoux","year":"1997","journal-title":"Stroke"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.bbr.2014.01.052","article-title":"Correlation between subacute sensorimotor deficits and brain edema in two mouse models of intracerebral hemorrhage","volume":"264","author":"Krafft","year":"2014","journal-title":"Behav. Brain Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.1161\/STROKEAHA.114.008560","article-title":"Soluble Epoxide Hydrolase in Hydrocephalus, Cerebral Edema, and Vascular Inflammation After Subarachnoid Hemorrhage","volume":"46","author":"Siler","year":"2015","journal-title":"Stroke"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"H1034","DOI":"10.1152\/ajpheart.00214.2010","article-title":"Roles of cytosolic Ca2+ concentration and myofilament Ca2+ sensitization in age-dependent cerebrovascular myogenic tone","volume":"299","author":"Charles","year":"2010","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Thorpe, R.B., Hubbell, M.C., Silpanisong, J., Williams, J.M., and Pearce, W.J. (2017). Chronic Hypoxia Attenuates the Vasodilator Efficacy of Protein Kinase G in Fetal and Adult Ovine Cerebral Arteries. Am. J. Physiol. Heart Circ. Physiol.","DOI":"10.1152\/ajpheart.00480.2016"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1152\/japplphysiol.00233.2009","article-title":"Effects of chronic hypoxia on soluble guanylate cyclase activity in fetal and adult ovine cerebral arteries","volume":"107","author":"Pearce","year":"2009","journal-title":"J. Appl. Physiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1152\/japplphysiol.00012.2014","article-title":"VEGF receptors mediate hypoxic remodeling of adult ovine carotid arteries","volume":"117","author":"Adeoye","year":"2014","journal-title":"J. Appl. Physiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.neuroimage.2019.03.034","article-title":"Ex vivo fetal brain MRI: Recent advances, challenges, and future directions","volume":"195","author":"Vasung","year":"2019","journal-title":"Neuroimage"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.placenta.2005.12.010","article-title":"Metabolism of synthetic steroids by the human placenta","volume":"28","author":"Murphy","year":"2007","journal-title":"Placenta"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pneurobio.2013.04.001","article-title":"Brain development in rodents and humans: Identifying benchmarks of maturation and vulnerability to injury across species","volume":"106","author":"Semple","year":"2013","journal-title":"Prog. Neurobiol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2169","DOI":"10.1093\/jn\/134.9.2169","article-title":"Maternal nutrition and fetal development","volume":"134","author":"Wu","year":"2004","journal-title":"J. Nutr."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1079\/PNS2005478","article-title":"Developmental programming of health and disease","volume":"65","year":"2006","journal-title":"Proc. Nutr. Soc."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/2\/680\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:10:03Z","timestamp":1760159403000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/2\/680"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,12]]},"references-count":92,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["ijms22020680"],"URL":"https:\/\/doi.org\/10.3390\/ijms22020680","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2021,1,12]]}}}