dc.contributor
[Oria M, Duru S, Fernandez-Alonso I] Center for Fetal and Placental Research, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, USA. [Figueira RL] Center for Fetal and Placental Research, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, USA. Laboratory of Experimental Fetal Surgery "Michael Harrison", Division of Pediatric Surgery, Department of Surgery and Anatomy, Ribeirao Preto Medical School, University of Sao Paulo-USP, Ribeirao Preto, Brazil. [Scorletti F] Center for Fetal and Placental Research, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, USA. Department of Pediatric Surgery, Hospital Bambino Gesu, Rome, Italy. [Turner LE] The Chicago Institute for Fetal Health, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, USA. Department of Pediatric Surgery, Northwestern University, Feinberg School of Medicine, Chicago, USA. [Fernandez-Martin A, Marotta M] Center for Fetal and Placental Research, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, USA. Laboratori de Bioenginyeria, Teràpia Cel•lular i Cirurgia en Malformacions Congènites, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain
dc.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
Oria, Marc
dc.contributor.author
Duru, Soner
dc.contributor.author
Figueira, Rebeca L
dc.contributor.author
Scorletti, Federico
dc.contributor.author
Turner, Lucas E
dc.contributor.author
Fernandez-Alonso, Irati
dc.contributor.author
Fernández Martín, Alejandra
dc.contributor.author
Marotta Baleriola, Mario
dc.date.accessioned
2025-10-24T08:53:09Z
dc.date.available
2025-10-24T08:53:09Z
dc.date.issued
2020-08-04T10:41:25Z
dc.date.issued
2020-08-04T10:41:25Z
dc.date.issued
2019-09-26
dc.identifier
Oria M, Duru S, Figueira RL, Scorletti F, Turner LE, Fernandez-Alonso I, et al. Cell necrosis, intrinsic apoptosis and senescence contribute to the progression of exencephaly to anencephaly in a mice model of congenital chranioschisis. Cell Death Dis. 2019 Sep 26;10:721.
dc.identifier
https://hdl.handle.net/11351/5134
dc.identifier
10.1038/s41419-019-1913-6
dc.identifier
000488854900011
dc.identifier.uri
http://hdl.handle.net/11351/5134
dc.description.abstract
Amniotic fluid; Neonatal mortality; Exencephaly
dc.description.abstract
Líquido amniótico; Mortalidad neonatal; Exencefalia
dc.description.abstract
Líquid amniòtic; Mortalitat neonatal; Exencefàlia
dc.description.abstract
Exencephaly/anencephaly is one of the leading causes of neonatal mortality and the most extreme open neural tube defect with no current treatments and limited mechanistic understanding. We hypothesized that exencephaly leads to a local neurodegenerative process in the brain exposed to the amniotic fluid as well as diffuse degeneration in other encephalic areas and the spinal cord. To evaluate the consequences of in utero neural tissue exposure, brain and spinal cord samples from E17 exencephalic murine fetuses (maternal intraperitoneal administration of valproic acid at E8) were analyzed and compared to controls and saline-injected shams (n = 11/group). Expression of apoptosis and senescence genes (p53, p21, p16, Rbl2, Casp3, Casp9) was determined by qRT-PCR and protein expression analyzed by western blot. Apoptosis was measured by TUNEL assay and PI/AV flow cytometry. Valproic acid at E8 induced exencephaly in 22% of fetuses. At E17 the fetuses exhibited the characteristic absence of cranial bones. The brain structures from exencephalic fetuses demonstrated a loss of layers in cortical regions and a complete loss of structural organization in the olfactory bulb, hippocampus, dental gyrus and septal cortex. E17 fetuses had reduced expression of NeuN, GFAP and Oligodendrocytes in the brain with primed microglia. Intrinsic apoptotic activation (p53, Caspase9 and 3) was upregulated and active Caspase3 localized to the layer of brain exposed to the amniotic fluid. Senescence via p21-Rbl2 was increased in the brain and in the spinal cord at the lamina I-II of the somatosensory dorsal horn. The current study characterizes CNS alterations in murine exencephaly and demonstrates that degeneration due to intrinsic apoptosis and senescence occurs in the directly exposed brain but also remotely in the spinal cord.
dc.description.abstract
This work was supported by Prof. Jose L. Peiro internal Cincinnati Children's Hospital funding.
dc.format
application/pdf
dc.format
application/pdf
dc.publisher
Springer Nature
dc.relation
Cell Death & Disease;10
dc.relation
https://www.nature.com/articles/s41419-019-1913-6
dc.rights
Attribution 4.0 International
dc.rights
http://creativecommons.org/licenses/by/4.0/
dc.rights
info:eu-repo/semantics/openAccess
dc.subject
Fetus - Cervell - Malformacions
dc.subject
Rates (Animals de laboratori)
dc.subject
Líquid amniòtic
dc.subject
DISEASES::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Congenital Abnormalities::Nervous System Malformations
dc.subject
ORGANISMS::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Eutheria::Rodentia::Muridae::Murinae::Mice::Mice, Mutant Strains::Mice, Neurologic Mutants
dc.subject
ANATOMY::Embryonic Structures::Fetus::Amniotic Fluid
dc.subject
ENFERMEDADES::enfermedades y anomalías neonatales congénitas y hereditarias::anomalías congénitas::malformaciones del sistema nervioso
dc.subject
ORGANISMOS::Eukaryota::animales::Chordata::vertebrados::mamíferos::Eutheria::Rodentia::Muridae::Murinae::ratones::ratones de cepas mutantes::ratones mutantes neurológicos
dc.subject
ANATOMÍA::estructuras embrionarias::feto::líquido amniótico
dc.title
Cell necrosis, intrinsic apoptosis and senescence contribute to the progression of exencephaly to anencephaly in a mice model of congenital chranioschisis
dc.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion
