Prenatal Origin of Hemiparetic Cerebral Palsy: How Often and Why?

PEDIATRICS ◽  
1991 ◽  
Vol 88 (5) ◽  
pp. 1059-1062
Author(s):  
KARIN B. NELSON

"Consider what must be accomplished during the course of fetal brain development. In effect, in a few months the entire work of hundreds of millions of years of evolution must be reachieved. . . . Tens of billions of neurons must be born. . . . These new cells must find their way to their anatomical destinations, sometimes moving over substantial distances in an embryo that is constantly changing in form. . . Once the cell is fixed in place, the axon must find its way to its own destination. . . . They must not only get where they are going and make a connection, but they must avoid making any number of other connections that they might wrongly make in places they pass. Each nerve cell must develop one or more of at least a dozen neurotransmitters. . . ." The product of that miracle is the most complicated object in the known universe, a human brain. In this "Decade of the Brain," we can anticipate the emergence of a great deal more information about how the nervous system develops, prenatally and thereafter, and how and when that development can go awry. That information will come from laboratories, clinics, and nurseries. Neuroimaging of the infant brain, a subject now producing a rich harvest in journals of pediatrics, neurology, radiology, and obstetrics, will contribute important new information about the processes of brain development in our species, the timing of derailment from the normal course of brain development, and some aspects of pathogenesis. Neuropathology and the enormous flowering of new approaches in the basic and clinical neurosciences will help in explication of the mechanisms of maldevelopment and early injury. And we can hope that identification of mechanisms will allow us to develop strategies to prevent at least some of the problems leading to prenatal damage of the developing human brain.

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Colleen P. E. Rollins ◽  
Jane R. Garrison ◽  
Maite Arribas ◽  
Aida Seyedsalehi ◽  
Zhi Li ◽  
...  

Abstract All perception is a construction of the brain from sensory input. Our first perceptions begin during gestation, making fetal brain development fundamental to how we experience a diverse world. Hallucinations are percepts without origin in physical reality that occur in health and disease. Despite longstanding research on the brain structures supporting hallucinations and on perinatal contributions to the pathophysiology of schizophrenia, what links these two distinct lines of research remains unclear. Sulcal patterns derived from structural magnetic resonance (MR) images can provide a proxy in adulthood for early brain development. We studied two independent datasets of patients with schizophrenia who underwent clinical assessment and 3T MR imaging from the United Kingdom and Shanghai, China (n = 181 combined) and 63 healthy controls from Shanghai. Participants were stratified into those with (n = 79 UK; n = 22 Shanghai) and without (n = 43 UK; n = 37 Shanghai) hallucinations from the PANSS P3 scores for hallucinatory behaviour. We quantified the length, depth, and asymmetry indices of the paracingulate and superior temporal sulci (PCS, STS), which have previously been associated with hallucinations in schizophrenia, and constructed cortical folding covariance matrices organized by large-scale functional networks. In both ethnic groups, we demonstrated a significantly shorter left PCS in patients with hallucinations compared to those without, and to healthy controls. Reduced PCS length and STS depth corresponded to focal deviations in their geometry and to significantly increased covariance within and between areas of the salience and auditory networks. The discovery of neurodevelopmental alterations contributing to hallucinations establishes testable models for these enigmatic, sometimes highly distressing, perceptions and provides mechanistic insight into the pathological consequences of prenatal origins.


2017 ◽  
Author(s):  
Helen Spiers ◽  
Eilis Hannon ◽  
Leonard C. Schalkwyk ◽  
Nicholas J. Bray ◽  
Jonathan Mill

ABSTRACTBackgroundEpigenetic processes play a key role in orchestrating transcriptional regulation during the development of the human central nervous system. We previously described dynamic changes in DNA methylation (5mC) occurring during human fetal brain development, but other epigenetic processes operating during this period have not been extensively explored. Of particular interest is DNA hydroxymethylation (5hmC), a modification that is enriched in the human brain and hypothesized to play an important role in neuronal function, learning and memory. In this study, we quantify 5hmC across the genome of 71 human fetal brain samples spanning 23 to 184 days post-conception.ResultsWe identify widespread changes in 5hmC occurring during human brain development, notable sex-differences in 5hmC in the fetal brain, and interactions between 5mC and 5hmC at specific sites. Finally, we identify loci where 5hmC in the fetal brain is associated with genetic variation.ConclusionsThis study represents the first systematic analysis of dynamic changes in 5hmC across neurodevelopment and highlights the potential importance of this modification in the human brain. A searchable database of our fetal brain 5hmC data is available as a resource to the research community at http://epigenetics.essex.ac.uk/fetalbrain2/.


2021 ◽  
Author(s):  
◽  
Monica P. Strawn

Two experiments were conducted to investigate molecular regulation that impacts fetal brain development in pigs. In the first experiment (Chapter 2), gene expression was profiled by RNA sequencing (RNA-seq) to examine the whole transcriptome of the male (M) and female (F) fetal brain at gestation day (d) 45, 60 and 90. The analysis showed fewer differentially expressed genes (DEGs) in the brain of male and female fetuses in earlier gestation (d45-d60) when compared to late gestation (d60-d90). The homeobox (HOX) A5 gene that regulates pattern formation in early development was in the top upregulated DEGs between d45 to d60 in fetuses of both sexes. This study also found HOX B5 and D3 genes were in the top upregulated genes between d45 and d60 of the fetal brain of females, but not males. The second experiment (Chapter 3) investigated DNA methylation in pigs. DNA methylation in the fetal brain of both sexes at the same three gestation days was performed by enzymatic methyl sequencing (EM-seq). Hotspots of methylation in specific chromosomal regions were observed in the analysis. The analysis identified 1,475 sites in the pig genome that were methylated in the fetal brain, irrespective of sex, during development. The same sites were methylated in a canonically correlated manner in the blood of the adult stage, both in sows and boars. This is consistent with the Dilman theory of developmental aging (DevAge), which suggests that aging and early development of the brain are regulated by common molecular processes. A comparative analysis (Chapter 4) compared the gene expression patterns in the fetal brain and placenta between pigs and mice. The analysis identified 112 genes that were expressed (mean FPKM > 10) in the fetal brain of both species but not expressed (mean FPKM < 1) in the placenta of either species, and 10 genes that were expressed in the placenta of both species but not expressed in the fetal brain. In-silico analysis of the transcription factor binding sites in the 500 bp of the upstream DNA of these common genes revealed that they were commonly regulated by the RE1 silencing transcription factor (REST), which is a multifaceted transcription factor that acts as a master regulator of neurogenesis as well as controls neural excitation and the aging processes.


US Neurology ◽  
2010 ◽  
Vol 05 (02) ◽  
pp. 89
Author(s):  
Hao Huang ◽  

Human brain anatomy is characterized by dramatic structural changes during fetal development. It is extraordinarily complex and yet its origin is asimple tubular structure. Revealing detailed anatomy at different stages of human fetal brain development not only aids in understanding this highlyordered process, but also provides clues to detect abnormalities caused by genetic or environmental factors. For example, the characterization ofwhite matter axon growth could provide important clues to understanding the inhomegeneity of white matter injuries in cerebral palsy. However,anatomical studies of human brain development during this period are surprisingly scarce, and histology-based atlases have only recently becomeavailable. Diffusion tensor imaging (DTI), a novel method of magnetic resonance imaging (MRI), is capable of delineating anatomical components withhigh contrast and revealing structures at the microscopic level. The volumetric measurement from 3D DTI data can quantify structural growth. Asdiscussed in this article, the fetal brain DTI database will be a valuable resource for human brain developmental study and will provide referencestandards for diagnostic radiology of premature newborns.


Author(s):  
M.V. Medvedev, O.I. Kozlova, À.Yu. Romanova

Fetal brain was retrospectively evaluated in 418 normal fetuses at 16–28 weeks of gestation. The multiplanar mode to obtain the axial cerebral plane and measured the width of the cavum septum pellucidum (CSP) and biparietal diameter (BD). All measurements of CSP were done from as the widest diameter across both borders in an inter-to inter fashion. The CSP width is increasing at second trimester of gestation. Normal range plotted on the reference range (mean, 5th and 95th percentiles) of fetal width CSP by measuring of its size may be useful for assessment of fetal brain development in the second trimester of gestation.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alexis Papariello ◽  
David Taylor ◽  
Ken Soderstrom ◽  
Karen Litwa

AbstractThe endocannabinoid system (ECS) plays a complex role in the development of neural circuitry during fetal brain development. The cannabinoid receptor type 1 (CB1) controls synaptic strength at both excitatory and inhibitory synapses and thus contributes to the balance of excitatory and inhibitory signaling. Imbalances in the ratio of excitatory to inhibitory synapses have been implicated in various neuropsychiatric disorders associated with dysregulated central nervous system development including autism spectrum disorder, epilepsy, and schizophrenia. The role of CB1 in human brain development has been difficult to study but advances in induced pluripotent stem cell technology have allowed us to model the fetal brain environment. Cortical spheroids resemble the cortex of the dorsal telencephalon during mid-fetal gestation and possess functional synapses, spontaneous activity, an astrocyte population, and pseudo-laminar organization. We first characterized the ECS using STORM microscopy and observed synaptic localization of components similar to that which is observed in the fetal brain. Next, using the CB1-selective antagonist SR141716A, we observed an increase in excitatory, and to a lesser extent, inhibitory synaptogenesis as measured by confocal image analysis. Further, CB1 antagonism increased the variability of spontaneous activity within developing neural networks, as measured by microelectrode array. Overall, we have established that cortical spheroids express ECS components and are thus a useful model for exploring endocannabinoid mediation of childhood neuropsychiatric disease.


Author(s):  
Rachel L. Leon ◽  
Imran N. Mir ◽  
Christina L. Herrera ◽  
Kavita Sharma ◽  
Catherine Y. Spong ◽  
...  

Abstract Children with congenital heart disease (CHD) are living longer due to effective medical and surgical management. However, the majority have neurodevelopmental delays or disorders. The role of the placenta in fetal brain development is unclear and is the focus of an emerging field known as neuroplacentology. In this review, we summarize neurodevelopmental outcomes in CHD and their brain imaging correlates both in utero and postnatally. We review differences in the structure and function of the placenta in pregnancies complicated by fetal CHD and introduce the concept of a placental inefficiency phenotype that occurs in severe forms of fetal CHD, characterized by a myriad of pathologies. We propose that in CHD placental dysfunction contributes to decreased fetal cerebral oxygen delivery resulting in poor brain growth, brain abnormalities, and impaired neurodevelopment. We conclude the review with key areas for future research in neuroplacentology in the fetal CHD population, including (1) differences in structure and function of the CHD placenta, (2) modifiable and nonmodifiable factors that impact the hemodynamic balance between placental and cerebral circulations, (3) interventions to improve placental function and protect brain development in utero, and (4) the role of genetic and epigenetic influences on the placenta–heart–brain connection. Impact Neuroplacentology seeks to understand placental connections to fetal brain development. In fetuses with CHD, brain growth abnormalities begin in utero. Placental microstructure as well as perfusion and function are abnormal in fetal CHD.


1996 ◽  
Vol 19 (2-3) ◽  
pp. 141-149 ◽  
Author(s):  
John H. Gilmore ◽  
Diana O. Perkins ◽  
Mark A. Kliewer ◽  
Marvin L. Hage ◽  
Susan G. Silva ◽  
...  

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Huban Thomas Rajarethnem ◽  
Kumar Megur Ramakrishna Bhat ◽  
Malsawmzuali Jc ◽  
Siva Kumar Gopalkrishnan ◽  
Ramesh Babu Mugundhu Gopalram ◽  
...  

Choline is an essential nutrient for humans which plays an important role in structural integrity and signaling functions. Docosahexaenoic acid (DHA) is a polyunsaturated fatty acid, highly enriched in cell membranes of the brain. Dietary intake of choline or DHA alone by pregnant mothers directly affects fetal brain development and function. But no studies show the efficacy of combined supplementation of choline and DHA on fetal neurodevelopment. The aim of the present study was to analyze fetal neurodevelopment on combined supplementation of pregnant dams with choline and DHA. Pregnant dams were divided into five groups: normal control [NC], saline control [SC], choline [C], DHA, and C + DHA. Saline, choline, and DHA were given as supplements to appropriate groups of dams. NC dams were undisturbed during entire gestation. On postnatal day (PND) 40, brains were processed for Cresyl staining. Pups from choline or DHA supplemented group showed significant (p<0.05) increase in number of neurons in hippocampus when compared to the same in NC and SC groups. Moreover, pups from C + DHA supplemented group showed significantly higher number of neurons (p<0.001) in hippocampus when compared to the same in NC and SC groups. Thus combined supplementation of choline and DHA during normal pregnancy enhances fetal hippocampal neurodevelopment better than supplementation of choline or DHA alone.


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