-
Acta Biochimica Et Biophysica Sinica Jun 2024Neural tube defects (NTDs) are characterized by the failure of neural tube closure during embryogenesis and are considered the most common and severe central nervous...
Neural tube defects (NTDs) are characterized by the failure of neural tube closure during embryogenesis and are considered the most common and severe central nervous system anomalies during early development. Recent microRNA (miRNA) expression profiling studies have revealed that the dysregulation of several miRNAs plays an important role in retinoic acid (RA)-induced NTDs. However, the molecular functions of these miRNAs in NTDs remain largely unidentified. Here, we show that miR-10a-5p is significantly upregulated in RA-induced NTDs and results in reduced cell growth due to cell cycle arrest and dysregulation of cell differentiation. Moreover, the cell adhesion molecule L1-like ( is identified as a direct target of miR-10a-5p in neural stem cells (NSCs) , and its expression is reduced in RA-induced NTDs. siRNA-mediated knockdown of intracellular affects cell proliferation and differentiation similar to those of miR-10a-5p overexpression, which further leads to the inhibition of the expressions of downstream ERK1/2 MAPK signaling pathway proteins. These cellular responses are abrogated by either increased expression of the direct target of miR-10a-5p ( ) or an ERK agonist such as honokiol. Overall, our study demonstrates that miR-10a-5p plays a major role in the process of NSC growth and differentiation by directly targeting , which in turn induces the downregulation of the ERK1/2 cascade, suggesting that miR-10a-5p and Chl1 are critical for NTD formation in the development of embryos.
PubMed: 38841745
DOI: 10.3724/abbs.2024078 -
Environmental Health : a Global Access... Jun 2024Spina bifida, a developmental malformation of the spinal cord, is associated with high rates of mortality and disability. Although folic acid-based preventive strategies...
BACKGROUND
Spina bifida, a developmental malformation of the spinal cord, is associated with high rates of mortality and disability. Although folic acid-based preventive strategies have been successful in reducing rates of spina bifida, some areas continue to be at higher risk because of chemical exposures. Bangladesh has high arsenic exposures through contaminated drinking water and high rates of spina bifida. This study examines the relationships between mother's arsenic exposure, folic acid, and spina bifida risk in Bangladesh.
METHODS
We conducted a hospital-based case-control study at the National Institute of Neurosciences & Hospital (NINS&H) in Dhaka, Bangladesh, between December 2016 and December 2022. Cases were infants under age one year with spina bifida and further classified by a neurosurgeon and imaging. Controls were drawn from children seen at NINS&H and nearby Dhaka Shishu Hospital. Mothers reported folic acid use during pregnancy, and we assessed folate status with serum assays. Arsenic exposure was estimated in drinking water using graphite furnace atomic absorption spectrophotometry (GF-AAS) and in toenails using inductively coupled plasma mass spectrometry (ICP-MS). We used logistic regression to examine the associations between arsenic and spina bifida. We used stratified models to examine the associations between folic acid and spina bifida at different levels of arsenic exposure.
RESULTS
We evaluated data from 294 cases of spina bifida and 163 controls. We did not find a main effect of mother's arsenic exposure on spina bifida risk. However, in stratified analyses, folic acid use was associated with lower odds of spina bifida (adjusted odds ratio [OR]: 0.50, 95% confidence interval [CI]: 0.25-1.00, p = 0.05) among women with toenail arsenic concentrations below the median value of 0.46 µg/g, and no association was seen among mothers with toenail arsenic concentrations higher than 0.46 µg/g (adjusted OR: 1.09, 95% CI: 0.52-2.29, p = 0.82).
CONCLUSIONS
Mother's arsenic exposure modified the protective association of folic acid with spina bifida. Increased surveillance and additional preventive strategies, such as folic acid fortification and reduction of arsenic, are needed in areas of high arsenic exposure.
Topics: Humans; Folic Acid; Bangladesh; Spinal Dysraphism; Case-Control Studies; Female; Arsenic; Infant; Male; Adult; Infant, Newborn; Pregnancy; Water Pollutants, Chemical; Maternal Exposure; Young Adult; Drinking Water
PubMed: 38831396
DOI: 10.1186/s12940-024-01091-1 -
Scientific Reports Jun 2024Chiari type 1 malformation is a neurological disorder characterized by an obstruction of the cerebrospinal fluid (CSF) circulation between the brain (intracranial) and...
Chiari type 1 malformation is a neurological disorder characterized by an obstruction of the cerebrospinal fluid (CSF) circulation between the brain (intracranial) and spinal cord (spinal) compartments. Actions such as coughing might evoke spinal cord complications in patients with Chiari type 1 malformation, but the underlying mechanisms are not well understood. More insight into the impact of the obstruction on local and overall CSF dynamics can help reveal these mechanisms. Therefore, our previously developed computational fluid dynamics framework was used to establish a subject-specific model of the intracranial and upper spinal CSF space of a healthy control. In this model, we emulated a single cough and introduced porous zones to model a posterior (OBS-1), mild (OBS-2), and severe posterior-anterior (OBS-3) obstruction. OBS-1 and OBS-2 induced minor changes to the overall CSF pressures, while OBS-3 caused significantly larger changes with a decoupling between the intracranial and spinal compartment. Coughing led to a peak in overall CSF pressure. During this peak, pressure differences between the lateral ventricles and the spinal compartment were locally amplified for all degrees of obstruction. These results emphasize the effects of coughing and indicate that severe levels of obstruction lead to distinct changes in intracranial pressure.
Topics: Arnold-Chiari Malformation; Cough; Humans; Hydrodynamics; Cerebrospinal Fluid; Computer Simulation; Cerebrospinal Fluid Pressure; Spinal Cord; Female
PubMed: 38830910
DOI: 10.1038/s41598-024-62374-8 -
Frontiers in Molecular Neuroscience 2024During the first month of pregnancy, the brain and spinal cord are formed through a process called neurulation. However, this process can be altered by low serum levels...
During the first month of pregnancy, the brain and spinal cord are formed through a process called neurulation. However, this process can be altered by low serum levels of folic acid, environmental factors, or genetic predispositions. In 2018, a surveillance study in Botswana, a country with a high incidence of human immunodeficiency virus (HIV) and lacking mandatory food folate fortification programs, found that newborns whose mothers were taking dolutegravir (DTG) during the first trimester of pregnancy had an increased risk of neural tube defects (NTDs). As a result, the World Health Organization and the U.S. Food and Drug Administration have issued guidelines emphasizing the potential risks associated with the use of DTG-based antiretroviral therapies during pregnancy. To elucidate the potential mechanisms underlying the DTG-induced NTDs, we sought to assess the potential neurotoxicity of DTG in stem cell-derived brain organoids. The gene expression of brain organoids developed in the presence of DTG was analyzed by RNA sequencing, Optical Coherence Tomography (OCT), Optical Coherence Elastography (OCE), and Brillouin microscopy. The sequencing data shows that DTG induces the expression of the folate receptor (FOLR1) and modifies the expression of genes required for neurogenesis. The Brillouin frequency shift observed at the surface of DTG-exposed brain organoids indicates an increase in superficial tissue stiffness. In contrast, reverberant OCE measurements indicate decreased organoid volumes and internal stiffness.
PubMed: 38828282
DOI: 10.3389/fnmol.2024.1394058 -
Archives of Razi Institute Dec 2023Klippel-Feil Syndrome (KFS) is a rare genetic disorder characterized by the abnormal development of the cervical spine, leading to the fusion of two or more cervical...
Klippel-Feil Syndrome (KFS) is a rare genetic disorder characterized by the abnormal development of the cervical spine, leading to the fusion of two or more cervical vertebrae. The syndrome presents diverse symptoms, including limited neck movement, chronic pain, and neurological manifestations such as limb numbness or weakness. The severity of KFS can vary significantly, and treatment primarily focuses on symptom management and preventing complications such as scoliosis or spinal cord compression. Surgical interventions are often necessary for patients with complex forms of the syndrome. Interestingly, Chiari 1 malformation, a cranial anomaly affecting the brainstem, can coincide anatomically with KFS. In this case report, we present the case of a 9-year-old patient who sought medical attention due to persistent, unchanging neck pain. The patient's medical history was notable for developmental delays and cervical restraint observed during physical examination. Magnetic resonance imaging (MRI) findings revealed hydrocephalus and brainstem descent, indicating the presence of Chiari 1 malformation. Comprehensive MRI and CT scans were performed, and a management plan was formulated, primarily involving cranial surgery and physiotherapy. Implementation of the treatment approach resulted in significant improvement in the patient's symptoms. This case highlights the significance of considering Chiari 1 malformation as a potential comorbidity in patients diagnosed with KFS who present with persistent neck pain. Early detection and appropriate management of both conditions are crucial for achieving favorable outcomes and enhancing the quality of life for affected individuals. Understanding the complex interplay between KFS and Chiari 1 malformation is essential for providing comprehensive care and tailored treatment strategies. Further research is warranted to elucidate the underlying mechanisms linking these two conditions and to explore optimal management approaches for patients with dual pathology. By reporting this case, we contribute to the existing literature and increase awareness among healthcare professionals regarding the potential coexistence of KFS and Chiari 1 malformation. Continued efforts in identifying associated anomalies and optimizing therapeutic interventions will aid in improving patient outcomes and ensuring optimal care for individuals affected by these conditions.
Topics: Klippel-Feil Syndrome; Humans; Child; Magnetic Resonance Imaging; Arnold-Chiari Malformation; Male; Tomography, X-Ray Computed; Neck Pain; Female
PubMed: 38828178
DOI: 10.32592/ARI.2023.78.6.1868 -
Neurology India Mar 2024
Topics: Humans; Arnold-Chiari Malformation
PubMed: 38817188
DOI: 10.4103/neurol-india.Neurol-India-D-24-00173 -
Neurology India Mar 2024
Topics: Humans; Magnetic Resonance Imaging; Neural Tube Defects; Neurosurgical Procedures
PubMed: 38817168
DOI: 10.4103/neurol-india.Neurol-India-D-24-00071 -
Journal of Cardiothoracic Surgery May 2024Neurofibromatosis type 1 is a genetic disease that affects multiple organs and systems, leading to various clinical manifestations. In Neurofibromatosis type 1, rare... (Review)
Review
BACKGROUND
Neurofibromatosis type 1 is a genetic disease that affects multiple organs and systems, leading to various clinical manifestations. In Neurofibromatosis type 1, rare intrathoracic meningoceles often occur alongside bone dysplasia. These meningoceles contain cerebrospinal fluid and can be mistakenly diagnosed as 'pleural effusion'.
CASE PRESENTATION
In this case report, we mistakenly identified 'cerebrospinal fluid' as 'pleural effusion' and proceeded with drainage. This error posed significant risks to the patient and holds valuable implications for the future diagnosis and treatment of similar patients.
CONCLUSIONS
In patients with Neurofibromatosis type 1 complicated by spinal deformity, there is a high incidence of intrathoracic meningoceles. Treatment strategies may differ based on the specific features of the lesions, and collaboration among multiple disciplines can significantly improve patient outcomes.
Topics: Humans; Neurofibromatosis 1; Meningocele; Diagnostic Errors; Pleural Effusion; Tomography, X-Ray Computed; Male; Female
PubMed: 38816890
DOI: 10.1186/s13019-024-02819-3 -
Journal of Developmental Biology Apr 2024The planar cell polarity (PCP) system is essential for positioning cells in 3D networks to establish the proper morphogenesis, structure, and function of organs during... (Review)
Review
The planar cell polarity (PCP) system is essential for positioning cells in 3D networks to establish the proper morphogenesis, structure, and function of organs during embryonic development. The PCP system uses inter- and intracellular feedback interactions between components of the core PCP, characterized by coordinated planar polarization and asymmetric distribution of cell populations inside the cells. PCP signaling connects the anterior-posterior to left-right embryonic plane polarity through the polarization of cilia in the Kupffer's vesicle/node in vertebrates. Experimental investigations on various genetic ablation-based models demonstrated the functions of PCP in planar polarization and associated genetic disorders. This review paper aims to provide a comprehensive overview of PCP signaling history, core components of the PCP signaling pathway, molecular mechanisms underlying PCP signaling, interactions with other signaling pathways, and the role of PCP in organ and embryonic development. Moreover, we will delve into the negative feedback regulation of PCP to maintain polarity, human genetic disorders associated with PCP defects, as well as challenges associated with PCP.
PubMed: 38804432
DOI: 10.3390/jdb12020012 -
Journal of Neurological Surgery Reports Apr 2024Diastematomyelia is a rare congenital disorder characterized by the separation of the spinal cord by an osseocartilaginous or fibrous septum. While diastematomyelia has...
Diastematomyelia is a rare congenital disorder characterized by the separation of the spinal cord by an osseocartilaginous or fibrous septum. While diastematomyelia has been reported to be more common in the thoracic and lumbar regions, the true incidence of cervical diastematomyelia is currently unknown. In this study, we conducted the most comprehensive systematic review to date of all other case reports of diastematomyelia to better characterize the incidence of cervical diastematomyelia and provide comprehensive statistics on the clinical characteristics of diastematomyelia generally. Ninety-one articles were included in our study, which comprised 252 males (27.9%) and 651 females (72.0%) (and one patient with unspecified gender). In 507 cases, the vertebral level of the diastematomyelia was described, and we recorded those levels as either cervical ( = 8, 1.6%), thoracic ( = 220, 43.4%), lumbar ( = 277, 54.6%), or sacral ( = 2, 0.4%). In 719 cases, the type of diastematomyelia was specified as either Type I ( = 482, 67.0%) or Type II ( = 237, 33.0%). Our study found that diastematomyelia has been reported in the cervical region in only 1.6% of cases, and we provide comprehensive data that this disorder occurs in female-to-male ratio of approximately 2.6:1 and Type I versus Type II diastematomyelia in an estimated ratio of 2:1.
PubMed: 38798790
DOI: 10.1055/a-2319-3444