{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T07:48:22Z","timestamp":1780732102636,"version":"3.54.1"},"reference-count":69,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,6,26]],"date-time":"2019-06-26T00:00:00Z","timestamp":1561507200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,6,26]],"date-time":"2019-06-26T00:00:00Z","timestamp":1561507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Offspring of preeclamptic pregnancies have cognitive alterations. Placental growth factor (PGF), is low in preeclampsia; reduced levels may affect brain development. PGF-null mice differ from normal congenic controls in cerebrovasculature, neuroanatomy and behavior. Using brain imaging and behavioral testing, we asked whether developmentally asynchronous (i.e. neonatal) PGF supplementation alters the vascular, neuroanatomic and\/or behavioral status of<jats:italic>Pgf<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>mice at adulthood. C57BL\/6-<jats:italic>Pgf<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>pups were treated intraperitoneally on postnatal days 1\u201310 with vehicle or PGF at 10\u2009pg\/g, 70\u2009pg\/g or 700\u2009pg\/g. These mice underwent behavioral testing and perfusion for MRI and analysis of retinal vasculature. A second cohort of vehicle- or PGF-treated mice was perfused for micro-CT imaging. 10\u2009pg\/g PGF-treated mice exhibited less locomotor activity and greater anxiety-like behavior relative to vehicle-treated mice. Depressive-like behavior showed a sex-specific, dose-dependent decrease and was lowest in 700\u2009pg\/g PGF-treated females relative to vehicle-treated females. Spatial learning did not differ. MRI revealed smaller volume of three structures in the 10\u2009pg\/g group, larger volume of seven structures in the 70\u2009pg\/g group and smaller volume of one structure in the 700\u2009pg\/g group. No cerebral or retinal vascular differences were detected. Overall, neonatal PGF replacement altered behavior and neuroanatomy of adult<jats:italic>Pgf<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>mice.<\/jats:p>","DOI":"10.1038\/s41598-019-45824-6","type":"journal-article","created":{"date-parts":[[2019,6,26]],"date-time":"2019-06-26T10:02:56Z","timestamp":1561543376000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Adult Pgf\u2212\/\u2212 mice behaviour and neuroanatomy are altered by neonatal treatment with recombinant placental growth factor"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8685-2348","authenticated-orcid":false,"given":"Vanessa R.","family":"Kay","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay S.","family":"Cahill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anas","family":"Hanif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G.","family":"Sled","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Carmeliet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandrakant","family":"Tayade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. Anne","family":"Croy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,6,26]]},"reference":[{"key":"45824_CR1","doi-asserted-by":"crossref","unstructured":"Powers, R. W. et al. Low placental growth factor across pregnancy identifies a subset of women with preterm preeclampsia: type 1 versus type 2 preeclampsia? Hypertension. 60(1), 239\u201346, PMID: 22647886 (2012).","DOI":"10.1161\/HYPERTENSIONAHA.112.191213"},{"key":"45824_CR2","doi-asserted-by":"crossref","unstructured":"Tidwell, S. C., Ho, H. N., Chiu, W. H., Torry, R. J. & Torry, D. S. Low maternal serum levels of placenta growth factor as an antecedent of clinical preeclampsia. Am J Obstet Gynecol. 184(6), 1267\u201372, PMID: 11349200 (2001).","DOI":"10.1067\/mob.2001.113129"},{"key":"45824_CR3","doi-asserted-by":"crossref","unstructured":"Torry, D. S., Wang, H. S., Wang, T. H., Caudle, M. R. & Torry, R. J. Preeclampsia is associated with reduced serum levels of placenta growth factor. Am J Obstet Gynecol. 179(6 Pt 1), 1539\u201344, PMID: 9855593 (1998).","DOI":"10.1016\/S0002-9378(98)70021-3"},{"key":"45824_CR4","doi-asserted-by":"crossref","unstructured":"Staff, A. C., Braekke, K., Harsem, N. K., Lyberg, T. & Holthe, M. R. Circulating concentrations of sFlt1 (soluble fms-like tyrosine kinase 1) in fetal and maternal serum during pre-eclampsia. Eur J Obstet Gynecol Reprod Biol. 122(1), 33\u20139, PMID: 15935542 (2005).","DOI":"10.1016\/j.ejogrb.2004.11.015"},{"issue":"1","key":"45824_CR5","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1080\/09513590.2016.1241228","volume":"33","author":"Ver\u00f3nica Paredes","year":"2016","unstructured":"Paredes, V. et al. Lower placental growth factor and higher free \u03b2-hCG and PAPP-A levels in the fetal circulation of near-term pregnancies complicated with severe preeclampsia. Gynecol Endocrinol. 33(1), 79\u201381, PMID: 27809614 (2017).","journal-title":"Gynecological Endocrinology"},{"key":"45824_CR6","doi-asserted-by":"crossref","unstructured":"Kocabas, A. M. et al. The transcriptome of human oocytes. Proc Natl Acad Sci USA 103(38), 14027\u201332, PMID: 16968779 (2006).","DOI":"10.1073\/pnas.0603227103"},{"key":"45824_CR7","doi-asserted-by":"crossref","unstructured":"Xie, D. et al. Rewirable gene regulatory networks in the preimplantation embryonic development of three mammalian species. Genome Res. 20(6), 804\u201315, PMID: 20219939 (2010).","DOI":"10.1101\/gr.100594.109"},{"key":"45824_CR8","doi-asserted-by":"crossref","unstructured":"Zeng, F., Baldwin, D. A. & Schultz, R. M. Transcript profiling during preimplantation mouse development. Dev Biol. 15; 272(2), 483\u201396, PMID: 15282163 (2004).","DOI":"10.1016\/j.ydbio.2004.05.018"},{"issue":"6","key":"45824_CR9","doi-asserted-by":"publisher","first-page":"1302","DOI":"10.1093\/humrep\/dev070","volume":"30","author":"N.E. Bergen","year":"2015","unstructured":"Bergen, N.E. et al. Early pregnancy maternal and fetal angiogenic factors and fetal and childhood growth: the Generation R Study. Hum Reprod. 30(6), 1302\u201313, PMID: 25854264 (2015).","journal-title":"Human Reproduction"},{"key":"45824_CR10","unstructured":"Kalampokas, E. et al. Association of adiponectin and placental growth factor in amniotic fluid with second trimester fetal growth. In Vivo. 26(2), 327\u201333, PMID: 22351679 (2012)."},{"issue":"1","key":"45824_CR11","doi-asserted-by":"publisher","first-page":"75","DOI":"10.3109\/14767058.2012.728646","volume":"26","author":"Thalis Papapostolou","year":"2012","unstructured":"Papapostolou, T. et al. Midtrimester amniotic fluid concentrations of angiogenic factors in relation to maternal, gestational and neonatal characteristics in normal pregnancies. J Matern Fetal Neonatal Med. 26(1), 75\u20138, PMID: 22963269 (2013).","journal-title":"The Journal of Maternal-Fetal & Neonatal Medicine"},{"key":"45824_CR12","doi-asserted-by":"crossref","unstructured":"Gishti, O. et al. Influence of maternal angiogenic factors during pregnancy on microvascular structure in school-age children. Hypertension. 65(4), 722\u20138, PMID: 25691621 (2015).","DOI":"10.1161\/HYPERTENSIONAHA.114.05008"},{"key":"45824_CR13","doi-asserted-by":"crossref","unstructured":"Ehrenstein, V., Rothman, K. J., Pedersen, L., Hatch, E. E. & S\u00f8rensen, H. T. Pregnancy-associated hypertensive disorders and adult cognitive function among Danish conscripts. Am J Epidemiol. 170(8), 1025\u20131031, PMID: 19726495 (2009).","DOI":"10.1093\/aje\/kwp223"},{"key":"45824_CR14","doi-asserted-by":"crossref","unstructured":"Many, A. et al. Neurodevelopmental and cognitive assessment of children born growth restricted to mothers with and without preeclampsia. Hypertens Pregnancy. 22(1), 25\u20139, PMID: 12648440 (2003).","DOI":"10.1081\/PRG-120016791"},{"key":"45824_CR15","doi-asserted-by":"crossref","unstructured":"R\u00e4tsep, M. T. et al. Impact of preeclampsia on cognitive function in the offspring. Behav Brain Res. 302. 175\u201381, PMID: 26784561 (2016a).","DOI":"10.1016\/j.bbr.2016.01.030"},{"key":"45824_CR16","doi-asserted-by":"crossref","unstructured":"Tuovinen, S. et al. Hypertensive disorders in pregnancy and intellectual abilities in the offspring in young adulthood: the Helsinki Birth Cohort Study. Ann Med. 44(4), 394\u2013403, PMID: 21495787 (2012a).","DOI":"10.3109\/07853890.2011.573497"},{"key":"45824_CR17","doi-asserted-by":"crossref","unstructured":"Tuovinen, S. et al. Hypertensive disorders in pregnancy and cognitive decline in the offspring up to old age. Neurology. 79(15), 1578\u201382, PMID: 23035059 (2012b).","DOI":"10.1212\/WNL.0b013e31826e2606"},{"key":"45824_CR18","doi-asserted-by":"crossref","unstructured":"Mann, J. R. & McDermott, S. Are maternal genitourinary infection and pre-eclampsia associated with ADHD in school-aged children? J Atten Disord. 15(8), 667\u201373, PMID: 20837984 (2011).","DOI":"10.1177\/1087054710370566"},{"key":"45824_CR19","doi-asserted-by":"crossref","unstructured":"Dachew, B.A., Mamun, A., Maravilla, J. C. & Alati, R. Pre-eclampsia and the risk of autism-spectrum disorder in offspring: meta-analysis. Br J Psychiatry. 24. 1\u20136, PMID: 29436313 (2018).","DOI":"10.26226\/morressier.5a7070ded462b80290b5678f"},{"key":"45824_CR20","doi-asserted-by":"crossref","unstructured":"Tuovinen, S. et al. Depressive symptoms in adulthood and intrauterine exposure to pre-eclampsia: the Helsinki Birth Cohort Study. BJOG. 117(10), 1236\u201342, PMID: 20560943 (2010).","DOI":"10.1111\/j.1471-0528.2010.02634.x"},{"key":"45824_CR21","doi-asserted-by":"crossref","unstructured":"R\u00e4tsep, M.T. et al. Brain structural and vascular anatomy is altered in offspring of pre-eclamptic pregnancies: A pilot study. AJNR Am J Neuroradiol. 37(5), 939\u201345, PMID: 26721772 (2016b).","DOI":"10.3174\/ajnr.A4640"},{"key":"45824_CR22","doi-asserted-by":"crossref","unstructured":"Kajantie, E., Eriksson, J. G., Osmond, C., Thornburg, K. & Barker, D. J. Pre-eclampsia is associated with increased risk of stroke in the adult offspring: the Helsinki birth cohort study. Stroke. 40(4), 1176\u201380, PMID: 19265049 (2009).","DOI":"10.1161\/STROKEAHA.108.538025"},{"key":"45824_CR23","doi-asserted-by":"crossref","unstructured":"Carmeliet, P. et al. Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions. Nat Med. 7(5), 575\u201383, PMID: 11329059 (2001).","DOI":"10.1038\/87904"},{"key":"45824_CR24","doi-asserted-by":"crossref","unstructured":"Luna, R. L. et al. Placental growth factor deficiency is associated with impaired cerebral vascular development in mice. Mol Hum Reprod. 22(2), 130\u201342, PMID: 26646502 (2016).","DOI":"10.1093\/molehr\/gav069"},{"key":"45824_CR25","doi-asserted-by":"crossref","unstructured":"Kay, V.R., Tayade, C., Carmeliet, P. & Croy, B. A. Influences of placental growth factor on mouse retinal vascular development. Dev Dyn. 246(9), 700\u2013712, PMID: 28646507 (2017).","DOI":"10.1002\/dvdy.24540"},{"key":"45824_CR26","doi-asserted-by":"crossref","unstructured":"Kay, V.R. et al. Effects of placental growth factor deficiency on behavior, neuroanatomy and cerebrovasculature of mice. Physiol Genomics. 50(10), 862\u2013875, PMID: 30118404 (2018).","DOI":"10.1152\/physiolgenomics.00076.2018"},{"key":"45824_CR27","doi-asserted-by":"crossref","unstructured":"Lecuyer, M. et al. PLGF, a placental marker of fetal brain defects after in utero alcohol exposure. Acta Neuropathol Commun. 5(1), 44, PMID: 2858768 (2017).","DOI":"10.1186\/s40478-017-0444-6"},{"key":"45824_CR28","doi-asserted-by":"crossref","unstructured":"Kolakowski, S. Jr et al. Placental growth factor provides a novel local angiogenic therapy for ischemic cardiomyopathy. J Card Surg. 21(6), 559\u201364, PMID: 17073953 (2006).","DOI":"10.1111\/j.1540-8191.2006.00296.x"},{"key":"45824_CR29","doi-asserted-by":"crossref","unstructured":"Luttun, A. et al. Revascularization of ischemic tissues by PlGF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Flt1. Nat Med. 8(8), 831\u201340, PMID: 12091877 (2002).","DOI":"10.1038\/nm731"},{"key":"45824_CR30","doi-asserted-by":"crossref","unstructured":"Roncal, C. et al. Beneficial effects of prolonged systemic administration of PlGF on late outcome of post-ischaemic myocardial performance. J Pathol. 216(2), 236\u201344, PMID: 18729077 (2008).","DOI":"10.1002\/path.2408"},{"key":"45824_CR31","doi-asserted-by":"crossref","unstructured":"Takeda, Y. et al. Treatment with recombinant placental growth factor (PlGF) enhances both angiogenesis and arteriogenesis and improves survival after myocardial infarction. Circ J. 73(9), 1674\u201382, PMID: 19602778 (2009).","DOI":"10.1253\/circj.CJ-08-1067"},{"key":"45824_CR32","doi-asserted-by":"crossref","unstructured":"Maglione, D., Battisti, M. & Tucci, M. Recombinant production of PIGF-1 and its activity in animal models. Farmaco. 55(3), 165\u20137, PMID: 10919072 (2000).","DOI":"10.1016\/S0014-827X(00)00012-4"},{"key":"45824_CR33","doi-asserted-by":"crossref","unstructured":"Hattori, H., Suzuki, S., Okazaki, Y., Suzuki, N. & Kuwana, M. Intracranial transplantation of monocyte-derived multipotential cells enhances recovery after ischemic stroke in rats. J Neurosci Res. 90(2), 479\u201388, PMID: 22057655 (2012).","DOI":"10.1002\/jnr.22755"},{"key":"45824_CR34","doi-asserted-by":"crossref","unstructured":"Liu, H. et al. Neuroprotection by PlGF gene-modified human mesenchymal stem cells after cerebral ischaemia. Brain. 129(Pt 10), 2734\u201345, PMID: 16901914 (2006).","DOI":"10.1093\/brain\/awl207"},{"issue":"5","key":"45824_CR35","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1182\/blood-2012-07-441527","volume":"122","author":"E. I. Gaal","year":"2013","unstructured":"Ga\u00e1l, E. I. et al. Comparison of vascular growth factors in the murine brain reveals placenta growth factor as prime candidate for CNS revascularization. Blood. 122(5), 658\u201365, PMID: 23803710 (2013).","journal-title":"Blood"},{"key":"45824_CR36","doi-asserted-by":"crossref","unstructured":"Aasa, K. L. et al. Placental growth factor influences maternal cardiovascular adaptation to pregnancy in mice. Biol Reprod. 92(2), 44, PMID: 25537372 (2015).","DOI":"10.1095\/biolreprod.114.124677"},{"key":"45824_CR37","doi-asserted-by":"crossref","unstructured":"Can, A. et al. The tail suspension test. J Vis Exp. (59), e3769, PMID: 22315011 (2012).","DOI":"10.3791\/3769-v"},{"key":"45824_CR38","doi-asserted-by":"crossref","unstructured":"Steru, L., Chermat, R., Thierry, B., Simon, P. The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology (Berl). 85(3), 367\u201370, PMID: 3923523 (1985).","DOI":"10.1007\/BF00428203"},{"key":"45824_CR39","doi-asserted-by":"crossref","unstructured":"Cahill, L.S. et al. Preparation of fixed mouse brains for MRI. Neuroimage. 60(2), 933\u20139, PMID: 22305951 (2012).","DOI":"10.1016\/j.neuroimage.2012.01.100"},{"key":"45824_CR40","doi-asserted-by":"crossref","unstructured":"de Guzman, A. E., Wong, M. D., Gleave, J. A. & Nieman, B. J. Variations in post-perfusion immersion fixation and storage alter MRI measurements of mouse brain morphometry. Neuroimage. 142. 687\u2013695, PMID: 27335314 (2016).","DOI":"10.1016\/j.neuroimage.2016.06.028"},{"key":"45824_CR41","doi-asserted-by":"crossref","unstructured":"Bock, N. A., Nieman, B. J., Bishop, J. B. & Henkelman, M. R. In vivo multiple-mouse MRI at 7 Tesla. Magn Reson Med. 54(5), 1311\u20136, PMID: 16215960 (2005),","DOI":"10.1002\/mrm.20683"},{"key":"45824_CR42","doi-asserted-by":"crossref","unstructured":"Dazai, J., Spring, S., Cahill, L. S., Henkelman, R. M. Multiple-mouse neuroanatomical magnetic resonance imaging. J Vis Exp. (48), pii: 2497 PMID: 21829155 (2011).","DOI":"10.3791\/2497"},{"key":"45824_CR43","doi-asserted-by":"crossref","unstructured":"Spencer Noakes, T. L., Henkelman, R. M. & Nieman, B. J. Partitioning k-space for cylindrical three-dimensional rapid acquisition with relaxation enhancement imaging in the mouse brain. NMR Biomed. 30(11), PMID: 28902423 (2017).","DOI":"10.1002\/nbm.3802"},{"key":"45824_CR44","doi-asserted-by":"crossref","unstructured":"Friedel, M., van Eede, M. C., Pipitone, J., Chakravarty, M. M. & Lerch, J. P. Pydpiper: a flexible toolkit for constructing novel registration pipelines. Front Neuroinform. 8. 67, PMID: 25126069 (2014).","DOI":"10.3389\/fninf.2014.00067"},{"key":"45824_CR45","doi-asserted-by":"crossref","unstructured":"Nieman, B. J. et al. MRI to Assess Neurological Function. Curr Protoc Mouse Biol. 8(2), e44, PMID: 29927554 (2018).","DOI":"10.1002\/cpmo.44"},{"key":"45824_CR46","doi-asserted-by":"crossref","unstructured":"Lerch, J. P. et al. Automated deformation analysis in the YAC128 Huntington disease mouse model. Neuroimage. 39(1), 32\u20139, PMID: 17942324 (2008).","DOI":"10.1016\/j.neuroimage.2007.08.033"},{"key":"45824_CR47","doi-asserted-by":"crossref","unstructured":"Nieman, B. J., Flenniken, A. M., Adamson, S. L., Henkelman, R. M. & Sled, J. G. Anatomical phenotyping in the brain and skull of a mutant mouse by magnetic resonance imaging and computed tomography. Physiol Genomics. 24(2), 154\u201362, PMID: 16410543 (2006).","DOI":"10.1152\/physiolgenomics.00217.2005"},{"key":"45824_CR48","doi-asserted-by":"crossref","unstructured":"Dorr, A. E., Lerch, J. P., Spring, S., Kabani, N. & Henkelman, R. M. High resolution three-dimensional brain atlas using an average magnetic resonance image of 40 adult C57Bl\/6J mice. Neuroimage. 42(1), 60\u20139, PMID: 18502665 (2008).","DOI":"10.1016\/j.neuroimage.2008.03.037"},{"key":"45824_CR49","doi-asserted-by":"crossref","unstructured":"Chakravarty, M. M. et al. Performing label-fusion-based segmentation using multiple automatically generated templates. Hum Brain Mapp. 34(10), 2635\u201354, PMID: 22611030 (2013).","DOI":"10.1002\/hbm.22092"},{"key":"45824_CR50","doi-asserted-by":"crossref","unstructured":"Ghanavati, S., Yu, L. X., Lerch, J. P. & Sled, J. G. A perfusion procedure for imaging of the mouse cerebral vasculature by X-ray micro-CT. J Neurosci Methods. 221. 70\u20137, PMID: 24056228 (2014).","DOI":"10.1016\/j.jneumeth.2013.09.002"},{"key":"45824_CR51","doi-asserted-by":"crossref","unstructured":"Chugh, B. P. et al. Measurement of cerebral blood volume in mouse brain regions using micro-computed tomography. Neuroimage. 47(4), 1312\u20138, PMID: 19362597 (2009).","DOI":"10.1016\/j.neuroimage.2009.03.083"},{"key":"45824_CR52","doi-asserted-by":"crossref","unstructured":"Rennie, M. Y. et al. Vessel tortuousity and reduced vascularization in the fetoplacental arterial tree after maternal exposure to polycyclic aromatic hydrocarbons. Am J Physiol Heart Circ Physiol. 300(2), H675\u201384, PMID: 21148768 (2011).","DOI":"10.1152\/ajpheart.00510.2010"},{"key":"45824_CR53","doi-asserted-by":"crossref","unstructured":"Zudaire, E., Gambardella, L., Kurcz, C. & Vermeren, S. A computational tool for quantitative analysis of vascular networks. PLoS One. 6(11), e27385, PMID: 22110636 (2011).","DOI":"10.1371\/journal.pone.0027385"},{"key":"45824_CR54","doi-asserted-by":"crossref","unstructured":"Makris, A. Placental growth factor reduces blood pressure in a uteroplacental ischemia model of preeclampsia in nonhuman primates. Hypertension. 67(6), 1263\u201372, PMID: 27091894 (2016).","DOI":"10.1161\/HYPERTENSIONAHA.116.07286"},{"key":"45824_CR55","doi-asserted-by":"crossref","unstructured":"Spradley, F. T. et al. Placental growth factor administration abolishes placental ischemia-induced hypertension. Hypertension. 67(4), 740\u20137, PMID: 26831193 (2016).","DOI":"10.1161\/HYPERTENSIONAHA.115.06783"},{"key":"45824_CR56","doi-asserted-by":"crossref","unstructured":"Suzuki, H. et al. Effect of recombinant placental growth factor 2 on hypertension induced by full-length mouse soluble fms-like tyrosine kinase 1 adenoviral vector in pregnant mice. Hypertension. 54(5), 1129\u201335, PMID: 19786649 (2009).","DOI":"10.1161\/HYPERTENSIONAHA.109.134668"},{"key":"45824_CR57","doi-asserted-by":"crossref","unstructured":"Adamcio, B., Sperling, S., Hagemeyer, N., Walkinshaw, G. & Ehrenreich, H. Hypoxia inducible factor stabilization leads to lasting improvement of hippocampal memory in healthy mice. Behav Brain Res. 208(1), 80\u20134, PMID: 19900484 (2010).","DOI":"10.1016\/j.bbr.2009.11.010"},{"key":"45824_CR58","doi-asserted-by":"crossref","unstructured":"Sun, J., Sha, B., Zhou, W. & Yang, Y. VEGF-mediated angiogenesis stimulates neural stem cell proliferation and differentiation in the premature brain. Biochem Biophys Res Commun. 394(1), 146\u201352, PMID: 20188072 (2010).","DOI":"10.1016\/j.bbrc.2010.02.132"},{"key":"45824_CR59","doi-asserted-by":"crossref","unstructured":"Carver, A. R. et al. Maternal pravastatin prevents altered fetal brain development in a preeclamptic CD-1 mouse model. PLoS One. 9(6), e100873, PMID: 24963809 (2014a).","DOI":"10.1371\/journal.pone.0100873"},{"key":"45824_CR60","doi-asserted-by":"crossref","unstructured":"Carver, A.R. et al. The effect of maternal pravastatin therapy on adverse sensorimotor outcomes of the offspring in a murine model of preeclampsia. Int J Dev Neurosci. 33. 33\u201340, PMID: 24287098 (2014b).","DOI":"10.1016\/j.ijdevneu.2013.11.004"},{"issue":"4","key":"45824_CR61","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.1073\/pnas.1011293108","volume":"108","author":"K. Kumasawa","year":"2010","unstructured":"Kumasawa, K. et al. Pravastatin induces placental growth factor (PGF) and ameliorates preeclampsia in a mouse model. Proc Natl Acad Sci USA 108(4), 1451\u20135, PMID: 21187414 (2011).","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"45824_CR62","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/j.braindev.2008.06.005","volume":"31","author":"S Jin-qiao","year":"2009","unstructured":"Jin-qiao, S., Bin, S., Wen-hao, Z. & Yi, Y. Basic fibroblast growth factor stimulates the proliferation and differentiation of neural stem cells in neonatal rats after ischemic brain injury. Brain Dev. 31, 331\u201340 (2009).","journal-title":"Brain Dev."},{"key":"45824_CR63","doi-asserted-by":"crossref","unstructured":"Naim, M.Y. et al. Folic acid enhances early functional recovery in a piglet model of pediatric head injury. Dev Neurosci. 32(5\u20136), 466\u201379, PMID: 21212637 (2010).","DOI":"10.1159\/000322448"},{"key":"45824_CR64","doi-asserted-by":"crossref","unstructured":"Robinson, S. et al. Extended Erythropoietin Treatment Prevents Chronic Executive Functional and Microstructural Deficits Following Early Severe Traumatic Brain Injury in Rats. Front Neurol. 9, 451, PMID: 29971038 (2018).","DOI":"10.3389\/fneur.2018.00451"},{"key":"45824_CR65","doi-asserted-by":"crossref","unstructured":"Hanson, J. L. et al. Structural variations in prefrontal cortex mediate the relationship between early childhood stress and spatial working memory. J Neurosci. 32(23), 7917\u201325, PMID: 22674267 (2012).","DOI":"10.1523\/JNEUROSCI.0307-12.2012"},{"key":"45824_CR66","doi-asserted-by":"crossref","unstructured":"Astle, D. E., Barnes, J. J., Baker, K., Colclough, G. L. & Woolrich, M. W. Cognitive training enhances intrinsic brain connectivity in childhood. J Neurosci. 35(16), 6277\u201383, PMID: 25904781 (2015).","DOI":"10.1523\/JNEUROSCI.4517-14.2015"},{"key":"45824_CR67","doi-asserted-by":"crossref","unstructured":"Cheng, L., Wang, S. H., Jia, N., Xie, M. & Liao, X. M. Environmental stimulation influence the cognition of developing mice by inducing changes in oxidative and apoptosis status. Brain Dev. 36(1), 51\u20136, PMID: 23273784 (2011).","DOI":"10.1016\/j.braindev.2012.11.015"},{"issue":"2","key":"45824_CR68","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.nlm.2006.09.001","volume":"87","author":"Jianli Yang","year":"2007","unstructured":"Yang, J. et al. Enriched environment treatment restores impaired hippocampal synaptic plasticity and cognitive deficits induced by prenatal chronic stress. Neurobiol Learn Mem. 87(2), 257\u201363, PMID: 17049888 (2007).","journal-title":"Neurobiology of Learning and Memory"},{"key":"45824_CR69","doi-asserted-by":"crossref","unstructured":"Schuch, C.P. et al. Early environmental enrichment affects neurobehavioral development and prevents brain damage in rats submitted to neonatal hypoxia-ischemia. Neurosci Lett. 617. 101\u20137, PMID: 26872850 (2016).","DOI":"10.1016\/j.neulet.2016.02.015"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-45824-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-45824-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-45824-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,17]],"date-time":"2023-09-17T19:38:37Z","timestamp":1694979517000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-45824-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,26]]},"references-count":69,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["45824"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-45824-6","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,26]]},"assertion":[{"value":"19 November 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 June 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 June 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"9285"}}