Valproic acid induced abnormal development of the central nervous system of three species of amphibians: Implications for neural tube defects and alternative experimental systems

Neural tube defects are rare and mostly lethal malformations. The pattern of inheritance of these malformations is multifactorial, rendering the identification of the underlying causes. Numerous studies have been conducted to elucidate the genetic basis of the development of the central nervous system. Essential signaling pathways of the development of the central nervous system include the planar cell polarity pathway, which is important for the initiation of neural tube closure as well as well as sonic hedhehog pathway, which regulates the neural plate bending. Genes and their mutations influencing the different stages of neurulation have been investigated for their eventual role in the development of these malformations. Among the environmental factors, folic acid seems to be the most important modifier of the risk of human neural tube defects. Genes of the folate metabolism pathways have also been investigated to identify mutations resulting in increased risk of NTDs. In this review the author has attempted to summarize the knowledge on neural tube defects, with special regard to genetic factors of the etiology.

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Neural Tube Defects

Pediatrics in Review ◽

10.1542/pir.1.6.187 ◽

1979 ◽

Vol 1 (6) ◽

pp. 187-190

Author(s):

Gerald S. Golden

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Neural Tube ◽

Neural Tube Defects ◽

Good Deal ◽

The United States ◽

Incidence Rates ◽

Number Of Factors ◽

The Central Nervous System ◽

Major Congenital Malformations

The term "neural tube defects" refers to a biologically interrelated series of malformations of the central nervous system and overlying tissues. There is an abnormality in morphogenesis of the brain and/or spinal cord, associated with varying degrees of absence or malformation of the meninges, bone, muscle, and skin. In addition to morphologic similarities, these lesions are related epidemiologically and probably genetically. The terminology is complex, but the lesions can be placed in a simple framework. The Table outlines the most common defects. The malformation occurs early in embryonic development, since the gross structure of the central nervous system has been completed by the 26th gestational day. There are numerous theories of pathogenesis and there is a good deal of subprimate teratologic research, but no single etiologic hypothesis is widely accepted or rigorously proven. Despite this, clinical risk factors have been clearly defined and empiric techniques for prenatal diagnosis have been developed. FREQUENCY AND EPIDEMIOLOGY Neural tube defects represent one of the most common groups of major congenital malformations. Each year approximately 6,000 to 8,000 infants are born with these conditions in the United States. Incidence rates vary among different groups from 0.6 to 4.1/1,000 total births for anencephaly. The risk is not uniformly spread over the entire population; a number of factors are related to initial occurrence and recurrence.

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DETERMINATION OF VALPROIC ACID IN TEAR BY GCQ -ASSESSEMENT OF THE CONCENTRATIONS OF DRUGS ACTING ON THE CENTRAL NERVOUS SYSTEM IN TEAR-

Drug Metabolism and Pharmacokinetics ◽

10.2133/dmpk.13.supplement_120 ◽

1998 ◽

Vol 13 (supplement) ◽

pp. 120-121

Author(s):

Masaharu NAKAJIMA ◽

Tomoko OHTA ◽

Nozomi KAWAKAMI ◽

Susumu YAMATO ◽

Kenji SHIMADA ◽

...

Keyword(s):

Central Nervous System ◽

Valproic Acid ◽

Nervous System ◽

The Central Nervous System

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Paediatric neuroscience care

Oxford Handbook of Neuroscience Nursing ◽

10.1093/med/9780198831570.003.0014 ◽

2020 ◽

pp. 467-492

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Neural Tube ◽

Neural Tube Defects ◽

Spinal Disorders ◽

Adult Services ◽

Central Nervous System Tumours ◽

Basic Understanding ◽

Craniofacial Syndromes

Paediatric neurology services care for children aged 0–16 years. Many of these children suffer genetic and complex neurological problems and frequently require life-long support. Hydrocephalus and central nervous system tumours are commonly presenting disorders; however, craniofacial syndromes, spinal disorders, spinal neural tube defects, epilepsy, and trauma including non-accidental injuries are frequently managed. Paediatric nurses specialize in the care of these children and support of their families but as they grow up and transition into adult services, it is the responsibility of general nurses to have a basic understanding of some of their conditions so they can maintain and continue their care.

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Malformation of the Brain, Skull, and Spine

10.1093/med/9780197512166.003.0117 ◽

2021 ◽

pp. 1057-1070

Author(s):

Lily C. Wong-Kisiel

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Developmental Delay ◽

Abnormal Development ◽

Gene Expressions ◽

Common Cause ◽

Genetic Causes ◽

The Central Nervous System ◽

The Brain ◽

Central Nervous System Malformation

Abnormal development of the central nervous system is a common cause of developmental delay and epilepsy. An understanding of central nervous system malformation begins with an overview of normal embryology. Genetic advances in embryogenesis have unfolded a complex orchestration of gene expressions in place of the traditional developmental epochs (induction, neurulation, proliferation, migration, organization, synaptogenesis, and myelination). Causes of malformation of the central nervous system are multifactorial. Genetic causes, vitamin excess or deficiency, infections, or teratogens any time during pregnancy may disturb the preprogrammed mechanisms.

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Developmental Overview of Central Neuroanatomy

10.1093/med/9780190237493.003.0003 ◽

2017 ◽

Author(s):

Peggy Mason

Keyword(s):

Spinal Cord ◽

Central Nervous System ◽

Cerebrospinal Fluid ◽

Nervous System ◽

Cerebral Cortex ◽

Neural Tube ◽

The Central Nervous System ◽

Dorsal Telencephalon ◽

Adult Spinal Cord ◽

The Brain

The central nervous system develops from a proliferating tube of cells and retains a tubular organization in the adult spinal cord and brain, including the forebrain. Failure of the neural tube to close at the front is lethal, whereas failure to close the tube at the back end produces spina bifida, a serious neural tube defect. Swellings in the neural tube develop into the hindbrain, midbrain, diencephalon, and telencephalon. The diencephalon sends an outpouching out of the cranium to form the retina, providing an accessible window onto the brain. The dorsal telencephalon forms the cerebral cortex, which in humans is enormously expanded by growth in every direction. Running through the embryonic neural tube is an internal lumen that becomes the cerebrospinal fluid–containing ventricular system. The effects of damage to the spinal cord and forebrain are compared with respect to impact on self and potential for improvement.

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Neuro-Osteology

Critical Reviews in Oral Biology & Medicine ◽

10.1177/10454411980090020501 ◽

1998 ◽

Vol 9 (2) ◽

pp. 224-244 ◽

Cited By ~ 77

Author(s):

I. Kjær

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Pituitary Gland ◽

Developmental Disorders ◽

Sella Turcica ◽

Axial Skeleton ◽

Abnormal Development ◽

Craniofacial Skeleton ◽

The Central Nervous System

Neuro-osteology stresses the biological connection during development between nerve and hard tissues. It is a perspective that has developed since associations were first described between pre-natal peripheral nerve tissue and initial osseous bone formation in the craniofacial skeleton (Kjær, 1990a). In this review, the normal connection between the central nervous system and the axial skeleton and between the peripheral nervous system and jaw formation are first discussed. The early central nervous system (the neural tube) and the axial skeleton from the lumbosacral region to the sella turcica forms a unit, since both types of tissue are developmentally dependent upon the notochord. In different neurological disorders, the axial skeleton, including the pituitary gland, is malformed in different ways along the original course of the notochord. Anterior to the pituitary gland/sella turcica region, the craniofacial skeleton develops from prechordal cartilage, invading mesoderm and neural crest cells. Also, abnormal development in the craniofacial region, such as tooth agenesis, is analyzed neuro-osteologically. Results from pre-natal investigations provide information on the post-natal diagnosis of children with congenital developmental disorders in the central nervous system. Examples of these are myelomeningocele and holoprosencephaly. Three steps are important in clinical neuro-osteology: (1) clinical definition of the region of an osseous or dental malformation, (2) embryological determination of the origin of that region and recollection of which neurological structure has developed from the same region, and (3) clinical diagnosis of this neurological structure. If neurological malformation is the first symptom, step 2 results in the determination of the osseous region involved, which in step 3 is analyzed clinically. The relevance of future neuro-osteological diagnostics is emphasized.

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Central Nervous System Congenital Malformations, Especially Neural Tube Defects in 29 Provinces, Metropolitan Cities and Autonomous Regions of China:

International Journal of Epidemiology ◽

10.1093/ije/19.4.978 ◽

1990 ◽

Vol 19 (4) ◽

pp. 978-982 ◽

Cited By ~ 57

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Neural Tube ◽

Neural Tube Defects ◽

Congenital Malformations ◽

Metropolitan Cities ◽

Autonomous Regions

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Mucormycosis of the Central Nervous System

Journal of Fungi ◽

10.3390/jof5030059 ◽

2019 ◽

Vol 5 (3) ◽

pp. 59 ◽

Cited By ~ 2

Author(s):

Chikley ◽

Ben-Ami ◽

Kontoyiannis

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Treatment Strategies ◽

Incidence Rates ◽

Patient Registries ◽

Experimental Systems ◽

Large Patient ◽

Patients With Diabetes ◽

The Central Nervous System ◽

Disseminated Disease

Mucormycosis involves the central nervous system by direct extension from infected paranasal sinuses or hematogenous dissemination from the lungs. Incidence rates of this rare disease seem to be rising, with a shift from the rhino-orbital-cerebral syndrome typical of patients with diabetes mellitus and ketoacidosis, to disseminated disease in patients with hematological malignancies. We present our current understanding of the pathobiology, clinical features, and diagnostic and treatment strategies of cerebral mucormycosis. Despite advances in imaging and the availability of novel drugs, cerebral mucormycosis continues to be associated with high rates of death and disability. Emerging molecular diagnostics, advances in experimental systems and the establishment of large patient registries are key components of ongoing efforts to provide a timely diagnosis and effective treatment to patients with cerebral mucormycosis.

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Experiments on the ‘Overgrowth’ Phenomenon in the Brain of Chick Embryos

Development ◽

10.1242/dev.7.2.122 ◽

1959 ◽

Vol 7 (2) ◽

pp. 122-127

Author(s):

Harry Bergquist

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Neural Tube ◽

Human Embryos ◽

Chick Embryos ◽

Cranial Cavity ◽

The Central Nervous System ◽

The Brain ◽

Rostral Part ◽

Exact Term

Patten (1952) described ‘a curious distortion of the central nervous system’ in human embryos measuring 5, 7, 12·5, 20, and 30 mm. in length, as well as in some pig embryos. The malformation was called ‘overgrowth of the neural tube’. Instead of the indecisive word ‘overgrowth’ the present writer suggests the more exact term ‘hypermorphosis’ should be used for this malformation. Patten described it in the following way: ‘the neural tube epithelium had started to grow wildly so that it became folded, and refolded on itself, as if it was crowded into a cranial space fairly normal in size and shape’. The phenomenon was most distinctly developed in the rostral part of the neural tube. In some cases the cranial cavity was expanded by the process, giving rise to a high-crowned skull. In other cases an encephalocoel was formed. In later papers (1953, 1957) Patten discussed this phenomenon further.

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