Bhlhe40/Sirt1 Axis-Regulated Mitophagy Is Implicated in All-Trans Retinoic Acid-Induced Spina Bifida Aperta

Neural tube defects (NTDs) are the most severe congenital malformations that result from failure of neural tube closure during early embryonic development, and the underlying molecular mechanisms remain elusive. Mitophagy is the best-known way of mitochondrial quality control. However, the role and regulation of mitophagy in NTDs have not yet been elucidated. In this study, we used an all-trans retinoic acid (ATRA)-induced rat model to investigate mitophagy and its underlying mechanism in spina bifida aperta (SBA). The results of western blot, immunofluorescence and RT-qPCR analyses indicated that mitophagy was impaired and Sirt1 was downregulated in SBA. Administration of resveratrol-a strong specific Sirt1 activator-activated Sirt1, thus attenuating autophagy suppression and ameliorating SBA. RNA-sequencing and bioinformatics analysis results indicated that transcriptional regulation played an important role in NTDs. A luciferase reporter assay was performed to demonstrate that the transcription factor Bhlhe40 directly bound to and negatively regulated Sirt1 expression. Further, we discovered that the Bhlhe40/Sirt1 axis regulated mitophagy in neural stem cells. Collectively, our results for the first time demonstrate that Bhlhe40/Sirt1 axis regulated mitophagy is implicated in ATRA-induced SBA. Our findings provide new insights into pathogenesis of NTDs and a basis for potential therapeutic targets for NTDs.

Open Neural Tube Defects: A Case Presentation of 30-year-old Secundigravida with Spina Bifida of the Fetus

Spina bifida is a neural tube defect that occurs in about 1 in 1,500 pregnancies. Open spinal defects are associated with paralysis, incontinence and hydrocephalus requiring postnatal shunting of the cerebrospinal fluid. Neural tube defects are preventable through preconceptional folic acid supplementation. Occasionally, the diagnosis is made during routine anomaly scan at 18-20 weeks of gestation, as the earliest signs of the anomaly can be seen at the end of first trimester. The information provided by ultrasound plays a crucial role in patient counseling and pregnancy management. The authors report a case of prenatal diagnosis of spina bifida aperta with focus on detailed ultrasound presentation and difficulties in consulting in relation to the prognosis for the newborns.

Transfection of STAT3 Overexpression Plasmid Mediated by Recombinant Lentivirus Promotes Differentiation of Bone Marrow Mesenchymal Stem Cells Into Neural Cells in Fetal Rats With Spina Bifida Aperta

Background To investigate the influence of signal transducer and activator of transcription-3 (STAT3) on spinal cord tissue grafts of rat fetuses with spina bifida aperta. In particular, we wished to determine if STAT3 overexpression plasmid transfection would increase survival of spinal cord transplantation to improve therapeutic efficiency. Methods The fetal rat model of spina bifida aperta was established by retinoic acid and treated by microsurgical injection of stem cells. They were divided into blank control group (n = 12), negative control group (n = 10) and experimental group (n = 11). The optical density (OD) value of BMSCs viability was determined by Cell Counting Kit-8 (CCK-8). The expression of STAT3, pSTAT3, nerve markers (Glial fibrillary acidic protein, Neuron-specific enolase, Neurofilament and Nestin) and apoptosis related factors (Caspase 8 and Bcl-2) were tested by the method of real-time PCR and Western blot. All statistical analyses were performed using SPSS version 20.0 software. One-way analysis of variance was used to analyze differences among three or more groups. The data are presented as the mean ± standard deviation from at least three independent experiments. P < 0.05 was considered statistically significant. Results OD value in experimental group was the highest at 8 hours after transplantation by CCK-8, and then gradually decreased, which was statistically significant compared with blank control group and negative control group (P < 0.05). There was no statistical difference in OD peak time and value between blank control group and negative control group. The expression levels of pSTAT3, Glial fibrillary acidic protein, Neuron-specific enolase, Neurofilament and Nestin in experimental group were remarkably higher than those in blank control group and negative control group (P < 0.05), but STAT3 expression in experimental group were statistically decreased (P < 0.05). The relative expression levels of Caspase-8 and Bcl-2 in experimental group were tremendously lower than those in blank control group and negative control group (P < 0.05). Conclusion Transfection of recombinant lentivirus mediated STAT3 overexpression plasmid with BMSCs can improve the efficiency of transforming into neural cells and provide new seed cells for the treatment of congenital spina bifida aperta.

Clinical Manifestation and Initial Management of Newborn with Spina Bifida Aperta: a case report.

Spina bifida is a birth defect that occurs due to the disruption of the formation of the neural tube with an incidence of 1–10 cases per 1000 live births. Spina bifida can appear as an occulta or aperta type, and the latter consists of meningocele, myelomeningocele, and myeloschisis. We reported a case of a term male newborn who was presented with lethargic, bradypnea, suction reflex abnormalities, and paralysis of lower extremities. A defect was found in the spine in the thoracolumbar region showed a placode with no meningeal and skin covering, suggestive of a myeloshisis. The patient was treated in the neonatal intensive care unit, was placed on non-invasive ventilation with successful weaning, parenteral nutrition, systemic antibiotics regimen, and wound care. The patient was consulted with a neurosurgeon and was subjected to an ultrasound examination of the head that led to hydrocephalus. After experienced clinical improvement and oral tolerance, the patient was allowed for discharged and scheduled for surgery.

Gambaran Kasus Spina Bifida di RSUD Arifin Achmad Provinsi Riau Periode 2015-2017

Spina bifida is a fault in the development of spine and the bones around until it leaves gap or defect in the spine. About 36 cases of spina bifida were involved in this research. The characteristis of spina bifida patients, mostly occurs at the patients at the age of > 28 days (83,3%). Most of them were male (52,8%). The most frequent spina bifida patients were the second child (44,4%) and location where spina bifida occurs were at the lumbosakral (72,2%). Classified into spina bifida aperta type (86,1%). The highest age of patients’ mother suffering from spina bifida was at the age of 20-40 (80,6%). In general, rupture didn’t occur on spina bifida patients (94.4%). The weight of spina bifida patients were between 2.500-4.000 gr (94,4%) and they didn’t have other congenital abnormalities (47,2%). The most gestational age of spina bifida patients’ mothers when giving birth were, is at 28-40 weeks (94.4%).

Anesthesia for Neonatal Myelomeningocele

Myelomeningocele, also known as spina bifida aperta (often shortened to the nonspecific name “spina bifida”) is a congenital disorder of the spine. In infants with a myelomeningocele, the neural tube has not closed, and the vertebral arches have not fused during development, leading to spinal cord and meningeal herniation through the skin. Because of the high potential for injury and infection of the exposed spinal cord, which could lead to lifetime disability, these lesions are typically repaired within 24 to 48 hours after birth. A myelomeningocele occurs before day 28 of human fetal development and is an abnormality in which the posterior neural tube closes incompletely. The outcome is a vertebral column deformity, through which the meningeal-lined sac herniates. After the bony defect is created, the hypothesized mechanism of meningeal herniation is that the pulsations of cerebrospinal fluid act progressively to balloon out the spinal cord. If the sac is filled with spinal nerves or the spinal cord, it is known as a myelomeningocele; if the sac is empty, it is called a meningocele.