Background:Magnetic resonance spectroscopy(MRS)represents a significant advancement in the noninvasive assessment of brain metabolism.MRS can provide valuable metabolic information and facilitate more accurate diagnos...Background:Magnetic resonance spectroscopy(MRS)represents a significant advancement in the noninvasive assessment of brain metabolism.MRS can provide valuable metabolic information and facilitate more accurate diagnoses of intrauterine fetal brain development than was previously possible.To obtain information regarding normal intrauterine fetal brain metabolism and to establish gestational age-specific reference values for normal fetal brain metabolites for subsequent use in MRS,we conducted MRS scans of normal fetal brains during mid-to late-term pregnancies,along with related processing.Methods:In this prospective study,MRS scans were conducted on 109 fetuses,with a total of 54 normal fetal brains enrolled on the basis of specific inclusion and exclusion criteria.We analyzed metabolic ratios,including the sum of N-acetylaspartate(NAA)and total N-acetylaspartate(tNAA),total choline(tCho),inositol(Ins),and total creatine(tCr),in relation to gestational age.Results:Gestational age was significantly correlated with specific metabolic ratios(Ins/tCr:r=-0.75,p<0.0001;tCho/tCr:r=-0.50,p<0.0001),especially tNAA/tCho(tNAA/tCho:r=0.54,p<0.0001)and tNAA/Ins(r=0.56,p<0.0001),providing a baseline for fetal brain metabolic assessment.Linear regression analysis was used to calculate regression lines for fetal brain metabolite ratios.Slopes were tested at p of 0.05.Conclusions:The current findings confirmed a significant correlation between fetal brain metabolites and gestational age,supporting the feasibility of establishing standard values for these metabolites in fetal brain assessment.展开更多
Central nervous system abnormalities in fetuses are fairly common,happening in 0.1%to 0.2%of live births and in 3%to 6%of stillbirths.So initial detection and categorization of fetal Brain abnormalities are critical.M...Central nervous system abnormalities in fetuses are fairly common,happening in 0.1%to 0.2%of live births and in 3%to 6%of stillbirths.So initial detection and categorization of fetal Brain abnormalities are critical.Manually detecting and segmenting fetal brain magnetic resonance imaging(MRI)could be timeconsuming,and susceptible to interpreter experience.Artificial intelligence(AI)algorithms and machine learning approaches have a high potential for assisting in the early detection of these problems,improving the diagnosis process and follow-up procedures.The use of AI and machine learning techniques in fetal brain MRI was the subject of this narrative review paper.Using AI,anatomic fetal brain MRI processing has investigated models to predict specific landmarks and segmentation automatically.All gestation age weeks(17-38 wk)and different AI models(mainly Convolutional Neural Network and U-Net)have been used.Some models'accuracy achieved 95%and more.AI could help preprocess and postprocess fetal images and reconstruct images.Also,AI can be used for gestational age prediction(with one-week accuracy),fetal brain extraction,fetal brain segmentation,and placenta detection.Some fetal brain linear measurements,such as Cerebral and Bone Biparietal Diameter,have been suggested.Classification of brain pathology was studied using diagonal quadratic discriminates analysis,Knearest neighbor,random forest,naive Bayes,and radial basis function neural network classifiers.Deep learning methods will become more powerful as more large-scale,labeled datasets become available.Having shared fetal brain MRI datasets is crucial because there aren not many fetal brain pictures available.Also,physicians should be aware of AI's function in fetal brain MRI,particularly neuroradiologists,general radiologists,and perinatologists.展开更多
Magnetic resonance imaging(MRI)is widely used to provide detailed information regarding fetal brain development in utero.Conventional T1-and T2-weighted sequences provide anatomical details of the normal brain and dem...Magnetic resonance imaging(MRI)is widely used to provide detailed information regarding fetal brain development in utero.Conventional T1-and T2-weighted sequences provide anatomical details of the normal brain and demonstrate brain lesions.In addition to providing highly detailed qualitative assessments of fetal brain development,advanced MRI methods such as threedimensional high-resolution MRI,diffusion MRI,magnetic resonance spectroscopy,and functional MRI can provide quantitative morphologic assessments of tissue microstructure and functional activity.This review aims to describe normal fetal brain development and highlight current state-of-the-art MRI sequences for fetal neuroimaging.We focus on current clinical applications which can provide a better understanding of in utero impairments in fetal brain development.展开更多
Although only about 2%of the human genome has proved to be protein-coding genes,recent advances in genome wide analysis have revealed that the majority of the genome is transcribed,mainly from noncoding segments that ...Although only about 2%of the human genome has proved to be protein-coding genes,recent advances in genome wide analysis have revealed that the majority of the genome is transcribed,mainly from noncoding segments that were once considered＂junk sequences＂or＂dark matters＂（Liu et al.,2011a;Zhang et al.,2014b）. In addition to the well-characterized housekeeping non- coding RNAs （ncRNAs） （tRNA, rRNA, small nuclear RNA and small nucleolar RNAs） and some small regulatory ncRNAs （microRNAs and small interfering RNAs）, the transcriptome of mammals could also pervasively have been transcribed long noncoding RNAs （lncRNAs, at least 200 nt） （Rinn and Chang, 2012; Xie et al., 2012）.展开更多
Application of modern magnetic resonance imaging(MRI) techniques to the live fetus in utero is a relatively recent endeavor. The relative advantages and disadvantages of clinical MRI relative to the widely used and ac...Application of modern magnetic resonance imaging(MRI) techniques to the live fetus in utero is a relatively recent endeavor. The relative advantages and disadvantages of clinical MRI relative to the widely used and accepted ultrasonographic approach are the subject of a continuing debate; however the focus of this review is on the even younger field of quantitative MRI as applied to non-invasive studies of fetal brain development. The techniques covered under this header include structural MRI when followed by quan-titative(e.g., volumetric) analysis, as well as quantita-tive analyses of diffusion weighted imaging, diffusion tensor imaging, magnetic resonance spectroscopy and functional MRI. The majority of the published work re-viewed here reflects information gathered from normal fetuses scanned during the 3rd trimester, with relatively smaller number of studies of pathological samples including common congenital pathologies such as ven-triculomegaly and viral infection.展开更多
Background: In recent years, there has been growing interest in the effect of maternal exposure to physiological, environmental, and also psychological factors during gestation on child development. Several independen...Background: In recent years, there has been growing interest in the effect of maternal exposure to physiological, environmental, and also psychological factors during gestation on child development. Several independent studies link maternal stress during pregnancy to emotional and behavioral problems in the child. Objectives: This study aimed to observe the effect of maternal cognitive activity on fetal brain blood flow to determine whether systematic maternal mathematical activity during pregnancy might influence child brain development. Method: Thirty-five women in the 28th to 40th week of pregnancy engaged in mathematical activities. Fetal middle cerebral artery (MCA), pulsatility index (PI) and peak systolic velocity (PSV) were monitored before, during, and after the activity. Results: Brain activity and blood flow were shown to be intimately linked. We observed a significant decrease in fetal brain MCA resistance, as evidenced by decreased MCA PI, towards the end of the mathematical activity. This may result in increased blood flow in the arteries supplying most brain regions and, possibly, increased brain activity. Conclusions: A correlation between the mother’s engagement in mathematical activities and fetal brain blood flow may lead to enhancement of the fetus’s brain function and a cognitive advantage for the child.展开更多
Several viral infections are often associated with fetal brain structural anomalies,including white matter lesions,cerebellar hypoplasia,temporal lobe lesions,ventricular dilatation,intraventricular septa,ependymal cy...Several viral infections are often associated with fetal brain structural anomalies,including white matter lesions,cerebellar hypoplasia,temporal lobe lesions,ventricular dilatation,intraventricular septa,ependymal cysts,and microcephaly,et al.Ultrasound(US)is the first modality of choice to evaluate fetal brain structural anomalies,however,Ultrasound is usually effected by maternal and fetal factors such as obesity,oligohydramnios and fetal head positions.Fetal MRI is not susceptible to the limitations as ultrasound with higher contrast resolution than prenatal ultrasound,directly visualize certain structures,such as developing brain parenchyma and further confirming US diagnosis and adding additional diagnostic information.This article reviews prenatal magnetic resonance imaging(MRI)diagnosis of fetal brain structural anomalies associated with viral infection.展开更多
Neuro D plays a key regulatory effect on differentiation of neural stem cells into mature neurons in the brain.Thus,we assumed that electroacupuncture at Baihui（DU20） acupoint in newborn rats exposed to in utero fet...Neuro D plays a key regulatory effect on differentiation of neural stem cells into mature neurons in the brain.Thus,we assumed that electroacupuncture at Baihui（DU20） acupoint in newborn rats exposed to in utero fetal distress would influence expression of Neuro D.Electroacupuncture at Baihui was performed for 20 minutes on 3-day-old（Day 3） newborn Sprague-Dawley rats exposed to in utero fetal distress;electroacupuncture parameters consisted of sparse and dense waves at a frequency of 2–10 Hz.Real-time fluorescent quantitative PCR results demonstrated that m RNA expression of Neuro D,a molecule that indicates Neuro D,increased with prolonged time in brains of newborn rats,and peaked on Day 22.The level of m RNA expression was similar between Day 16 and Day 35.These findings suggest that electro acupuncture at Baihui acupoint could effectively increase m RNA expression of molecules involved in Neuro D in the brains of newborn rats exposed to in utero fetal distress.展开更多
Fetal cells can enter maternal blood during pregnancy but whether they can also cross the blood-brain barrier to enter the maternal brain remains poorly understood. Previous results suggest that fetal cells are summon...Fetal cells can enter maternal blood during pregnancy but whether they can also cross the blood-brain barrier to enter the maternal brain remains poorly understood. Previous results suggest that fetal cells are summoned to repair damage to the mother＇s brain. If this is confirmed, it would open up new and safer avenues of treatment for brain damage caused by strokes and neural diseases. In this study, we aimed to investigate whether a baby＇s stem cells can enter the maternal brain during pregnancy. Deceased patients who had at least one male offspring and no history of abortion and blood transfusion were included in this study. DNA was extracted from brain tissue samples of deceased women using standard phenol-chloroform extraction and ethanol precipitation methods. Genomic DNA was screened by quantitative fluorescent-polymerase chain reaction amplification together with short tandem repeat markers specific to the Y chromosome, and 13, 18, 21 and X. Any foreign DNA residues that could be used to interpret the presence of fetal stem cells in the maternal brain were monitored. Results indicated that fetal stem cells can not cross the blood-brain barrier to enter the maternal brain.展开更多
The pathology of fetal alcohol syndrome and the less severe fetal alcohol spectrum disorders includes brain dysmyelination.Recent studies have shed light on the molecular mechanisms underlying these white matter abnor...The pathology of fetal alcohol syndrome and the less severe fetal alcohol spectrum disorders includes brain dysmyelination.Recent studies have shed light on the molecular mechanisms underlying these white matter abnormalities.Rodent models of fetal alcohol syndrome and human studies have shown suppressed oligodendrocyte differentiation and apoptosis of oligodendrocyte precursor cells.Ethanol exposure led to reduced expression of myelin basic protein and delayed myelin basic protein expression in rat and mouse models of fetal alcohol syndrome and in human histopathological specimens.Several studies have reported increased expression of many chemokines in dysmyelinating disorders in central nervous system,including multiple sclerosis and fetal alcohol syndrome.Acute ethanol exposure reduced levels of the neuroprotective insulin-like growth factor-1 in fetal and maternal sheep and in human fetal brain tissues,while ethanol increased the expression of tumor necrosis factor α in mouse and human neurons.White matter lesions have been induced in the developing sheep brain by alcohol exposure in early gestation.Rat fetal alcohol syndrome models have shown reduced axon diameters,with thinner myelin sheaths,as well as reduced numbers of oligodendrocytes,which were also morphologically aberrant oligodendrocytes.Expressions of markers for mature myelination,including myelin basic protein,also were reduced.The accumulating knowledge concerning the mechanisms of ethanol-induced dysmyelination could lead to the development of strategies to prevent dysmyelination in children exposed to ethanol during fetal development.Future studies using fetal oligodendrocyte-and oligodendrocyte precursor cell-derived exosomes isolated from the mother's blood may identify biomarkers for fetal alcohol syndrome and even implicate epigenetic changes in early development that affect oligodendrocyte precursor cell and oligodendrocyte function in adulthood.By combining various imaging modalities with molecular studies,it may be possible to determine which fetuses are at risk and to intervene therapeutically early in the pregnancy.展开更多
It is widely assumed that fetal ischemic brain injury during labor derives almost exclusively from severe, systemic hypoxemia with marked neonatal depression and acidemia. Severe asphyxia, however, is one of several c...It is widely assumed that fetal ischemic brain injury during labor derives almost exclusively from severe, systemic hypoxemia with marked neonatal depression and acidemia. Severe asphyxia, however, is one of several causes of perinatal neurological injury and may not be the most common;most neonates diagnosed with hypoxic-ischemic encephalopathy do not have evidence of severe asphyxia. Sepsis, direct brain trauma, and drug or toxin exposure account for some cases, while mechanical forces of labor and delivery that increase fetal intracranial pressure sufficiently to impair brain perfusion may also contribute. Because of bony compliance and mobile suture lines, the fetal skull changes shape and redistributes cerebrospinal fluid during labor according to constraints imposed by contractions, and bony and soft tissue elements of the birth canal as the head descends. These accommodations, including the increase in intracranial pressure, are adaptive and necessary for efficient descent of the head while safeguarding cerebral blood flow. Autonomic reflexes mediated through central receptors normally provide ample protection of the brain from the considerable pressure exerted on the skull. On occasion, those forces, which are transmitted intracranially, may overcome the various adaptive anatomical, cardiovascular, metabolic, and neurological mechanisms that maintain cerebral perfusion and oxygen availability, resulting in ischemic brain injury. Accepting the notion of a potentially adverse impact of fetal head compression suggests that avoidance of excessive uterine activity and of relentless pushing without steady progress in descent may offer protection for the fetal brain during parturition. Excessive head compression should be considered in the differential diagnosis of ischemic encephalopathy.展开更多
From pregnancy to parturition, Sprague-Dawley rats were daily administered a low protein diet to establish a model of intrauterine growth restriction. From the 12th day of pregnancy, 300 mg/kg taurine was daily added ...From pregnancy to parturition, Sprague-Dawley rats were daily administered a low protein diet to establish a model of intrauterine growth restriction. From the 12th day of pregnancy, 300 mg/kg taurine was daily added to food until spontaneous delivery occurred. Brain tissues from normal neonatal rats at 6 hours after delivery, neonatal rats with intrauterine growth restriction, and neo- natal rats with intrauterine growth restriction undergoing taurine supplement were obtained for fur- ther experiments. The terminal deoxyribonucleotidyl transferase （TdT）-mediated biotin-16-dUTP nick-end labeling assay revealed that the number of apoptotic cells in the brain tissue of neonatal rats with intrauterine growth restriction significantly increased. Taurine supplement in pregnant rats reduced cell apoptosis in brain tissue from neonatal rats with intrauterine growth restriction. Immu- nohistochemical staining revealed that taurine supplement increased glial cell line-derived neuro- trophic factor expression and decreased caspase-3 expression in the cerebral cortex of intrauterine growth-restricted fetal rats. These results indicate that taurine supplement reduces cell apoptosis through the glial cell line-derived neurotrophic factor-caspase-3 signaling pathway, resulting in a protective effect on the intrauterine growth-restricted fetal rat brain.展开更多
Dexmedetomidine has significant neuroprotective effects. However, whether its protective effects can reduce neurotoxicity caused by isoflurane in fetal brain during the second trimester of pregnancy remains unclear. I...Dexmedetomidine has significant neuroprotective effects. However, whether its protective effects can reduce neurotoxicity caused by isoflurane in fetal brain during the second trimester of pregnancy remains unclear. In this study, timed-pregnancy rats at gestational day 14 spontaneously inhaled 1.5% isoflurane for 4 hours, and were intraperitoneally injected with dexmedetomidine at dosages of 5, 10, 20, and 20 μg/kg 15 minutes before inhalation and after inhalation for 2 hours. Our results demonstrate that 4 hours after inhaling isoflurane, 20 μg/kg dexmedetomidine visibly mitigated isoflurane-induced neuronal apoptosis, reversed downregulation of brain-derived neurotrophic factor expression, and lessened decreased spatial learning and memory ability in adulthood in the fetal rats. Altogether, these findings indicate that dexmedetomidine can reduce neurodegeneration induced by isoflurane in fetal rats during the second trimester of pregnancy. Further, brain-derived neurotrophic factor participates in this process.展开更多
Maternal health during pregnancy has a direct impact on the risk and severity of neurodevelopmental disorders(NDDs)in the offspring,especially in the case of drug exposure.However,little progress has been made to asse...Maternal health during pregnancy has a direct impact on the risk and severity of neurodevelopmental disorders(NDDs)in the offspring,especially in the case of drug exposure.However,little progress has been made to assess the risk of drug exposure during pregnancy due to ethical constraints and drug use factors.We collected and manually curated sub-pathways and pathways(sub-/pathways)and drug information to propose an analytical framework for predicting drug candidates.This framework linked sub-/pathway activity and drug response scores derived from gene transcription data and was applied to human fetal brain development and six NDDs.Further,specific and pleiotropic sub-/pathways/drugs were identified using entropy,and sex bias was analyzed in conjunction with logistic regression and random forest models.We identified 19 disorder-associated and 256 regionally pleiotropic and specific candidate drugs that targeted risk sub-/pathways in NDDs,showing temporal or spatial changes across fetal development.Moreover,5443 differential drug-sub-/pathways exhibited sex-biased differences after filling in the gender labels.A user-friendly NDDP visualization website(https://ndd-lab.shinyapps.io/NDDP)was developed to allow researchers and clinicians to access and retrieve data easily.Our framework overcame data gaps and identified numerous pleiotropic and specific candidates across six disorders and fetal developmental trajectories.This could significantly contribute to drug discovery during pregnancy and can be applied to a wide range of traits.展开更多
Objective: Mortality in FASD has not been well studied. In this paper we review published reports of mortality in FASD. Method: We searched using Pub Med for all years in all languages for reports of all-cause mortali...Objective: Mortality in FASD has not been well studied. In this paper we review published reports of mortality in FASD. Method: We searched using Pub Med for all years in all languages for reports of all-cause mortality associated with any FASD. Results: We located 26 papers reporting on 57 deaths. Cause of death was reported for 49/57 cases (86%). The two most prevalent potential causes of death were malformations of the heart (37 of 49 cases, 75.5%) which varied from atrial septal defect or patent ductus arteriosus to tetralogy of Fallot, hypoplastic left heart, aortic arch interruption, etc. and brain malformations(25 of 49, 51%) including microcephaly, hydrocephalus, porencephaly, agenesis/absence of the corpus callosum and semilobar holoprosencephaly. In several cases potential causal findings overlapped. The three most frequent other causes of death were sepsis (7 cases, 14.3%), kidney malformations (7 cases, 14.3%), and cancer (4 cases, 8.2%). Over half the deaths (30/55, 54.5%) occurred in the first year of life. Discussion: We found that congenital heart disease was the most common cause of death in people with FASD. This may be due to an ascertainment bias since many of the published studies were focused on congenital heart disease in FASD. We conclude that FASD is frequently undetected in mortality events and could be a common finding in infant, child, adolescent and adult mortality.展开更多
基金supported by China Society for Maternal and Child Health Research(Gant/Award Number:2023CAMCHS003A17).
文摘Background:Magnetic resonance spectroscopy(MRS)represents a significant advancement in the noninvasive assessment of brain metabolism.MRS can provide valuable metabolic information and facilitate more accurate diagnoses of intrauterine fetal brain development than was previously possible.To obtain information regarding normal intrauterine fetal brain metabolism and to establish gestational age-specific reference values for normal fetal brain metabolites for subsequent use in MRS,we conducted MRS scans of normal fetal brains during mid-to late-term pregnancies,along with related processing.Methods:In this prospective study,MRS scans were conducted on 109 fetuses,with a total of 54 normal fetal brains enrolled on the basis of specific inclusion and exclusion criteria.We analyzed metabolic ratios,including the sum of N-acetylaspartate(NAA)and total N-acetylaspartate(tNAA),total choline(tCho),inositol(Ins),and total creatine(tCr),in relation to gestational age.Results:Gestational age was significantly correlated with specific metabolic ratios(Ins/tCr:r=-0.75,p<0.0001;tCho/tCr:r=-0.50,p<0.0001),especially tNAA/tCho(tNAA/tCho:r=0.54,p<0.0001)and tNAA/Ins(r=0.56,p<0.0001),providing a baseline for fetal brain metabolic assessment.Linear regression analysis was used to calculate regression lines for fetal brain metabolite ratios.Slopes were tested at p of 0.05.Conclusions:The current findings confirmed a significant correlation between fetal brain metabolites and gestational age,supporting the feasibility of establishing standard values for these metabolites in fetal brain assessment.
基金Supported by Colonel Robert R McCormick Professorship of Diagnostic Imaging Fund at Rush University Medical Center(The Activity Number is 1233-161-84),No.8410152-03.
文摘Central nervous system abnormalities in fetuses are fairly common,happening in 0.1%to 0.2%of live births and in 3%to 6%of stillbirths.So initial detection and categorization of fetal Brain abnormalities are critical.Manually detecting and segmenting fetal brain magnetic resonance imaging(MRI)could be timeconsuming,and susceptible to interpreter experience.Artificial intelligence(AI)algorithms and machine learning approaches have a high potential for assisting in the early detection of these problems,improving the diagnosis process and follow-up procedures.The use of AI and machine learning techniques in fetal brain MRI was the subject of this narrative review paper.Using AI,anatomic fetal brain MRI processing has investigated models to predict specific landmarks and segmentation automatically.All gestation age weeks(17-38 wk)and different AI models(mainly Convolutional Neural Network and U-Net)have been used.Some models'accuracy achieved 95%and more.AI could help preprocess and postprocess fetal images and reconstruct images.Also,AI can be used for gestational age prediction(with one-week accuracy),fetal brain extraction,fetal brain segmentation,and placenta detection.Some fetal brain linear measurements,such as Cerebral and Bone Biparietal Diameter,have been suggested.Classification of brain pathology was studied using diagonal quadratic discriminates analysis,Knearest neighbor,random forest,naive Bayes,and radial basis function neural network classifiers.Deep learning methods will become more powerful as more large-scale,labeled datasets become available.Having shared fetal brain MRI datasets is crucial because there aren not many fetal brain pictures available.Also,physicians should be aware of AI's function in fetal brain MRI,particularly neuroradiologists,general radiologists,and perinatologists.
基金Natural Science Foundation of Shanghai,Grant/Award Number:19ZR1476700National Natural Science Foundation of China,Grant/Award Numbers:81571628,81971582Shanghai Pujiang Program,Grant/Award Number:2019PJD030。
文摘Magnetic resonance imaging(MRI)is widely used to provide detailed information regarding fetal brain development in utero.Conventional T1-and T2-weighted sequences provide anatomical details of the normal brain and demonstrate brain lesions.In addition to providing highly detailed qualitative assessments of fetal brain development,advanced MRI methods such as threedimensional high-resolution MRI,diffusion MRI,magnetic resonance spectroscopy,and functional MRI can provide quantitative morphologic assessments of tissue microstructure and functional activity.This review aims to describe normal fetal brain development and highlight current state-of-the-art MRI sequences for fetal neuroimaging.We focus on current clinical applications which can provide a better understanding of in utero impairments in fetal brain development.
基金supported by the grants from the National Key Research and Development Plan (2016YFA0100702,2016YFC0902502)the National Key Basic Research Program (973 Program) (Nos.2013CB531304 and 2011CBA01104)+1 种基金the National Sciences Foundation of China (Nos. 31301152,31670789,31671316,31370789 and 30825023)CAMS Innovation Fund for Medical Sciences (CIFMS,2016-I2M-2-001,2016-I2M-1-001,2016-I2M-1-004)
文摘Although only about 2%of the human genome has proved to be protein-coding genes,recent advances in genome wide analysis have revealed that the majority of the genome is transcribed,mainly from noncoding segments that were once considered＂junk sequences＂or＂dark matters＂（Liu et al.,2011a;Zhang et al.,2014b）. In addition to the well-characterized housekeeping non- coding RNAs （ncRNAs） （tRNA, rRNA, small nuclear RNA and small nucleolar RNAs） and some small regulatory ncRNAs （microRNAs and small interfering RNAs）, the transcriptome of mammals could also pervasively have been transcribed long noncoding RNAs （lncRNAs, at least 200 nt） （Rinn and Chang, 2012; Xie et al., 2012）.
文摘Application of modern magnetic resonance imaging(MRI) techniques to the live fetus in utero is a relatively recent endeavor. The relative advantages and disadvantages of clinical MRI relative to the widely used and accepted ultrasonographic approach are the subject of a continuing debate; however the focus of this review is on the even younger field of quantitative MRI as applied to non-invasive studies of fetal brain development. The techniques covered under this header include structural MRI when followed by quan-titative(e.g., volumetric) analysis, as well as quantita-tive analyses of diffusion weighted imaging, diffusion tensor imaging, magnetic resonance spectroscopy and functional MRI. The majority of the published work re-viewed here reflects information gathered from normal fetuses scanned during the 3rd trimester, with relatively smaller number of studies of pathological samples including common congenital pathologies such as ven-triculomegaly and viral infection.
文摘Background: In recent years, there has been growing interest in the effect of maternal exposure to physiological, environmental, and also psychological factors during gestation on child development. Several independent studies link maternal stress during pregnancy to emotional and behavioral problems in the child. Objectives: This study aimed to observe the effect of maternal cognitive activity on fetal brain blood flow to determine whether systematic maternal mathematical activity during pregnancy might influence child brain development. Method: Thirty-five women in the 28th to 40th week of pregnancy engaged in mathematical activities. Fetal middle cerebral artery (MCA), pulsatility index (PI) and peak systolic velocity (PSV) were monitored before, during, and after the activity. Results: Brain activity and blood flow were shown to be intimately linked. We observed a significant decrease in fetal brain MCA resistance, as evidenced by decreased MCA PI, towards the end of the mathematical activity. This may result in increased blood flow in the arteries supplying most brain regions and, possibly, increased brain activity. Conclusions: A correlation between the mother’s engagement in mathematical activities and fetal brain blood flow may lead to enhancement of the fetus’s brain function and a cognitive advantage for the child.
基金supported by[National Natural Science Foundation of China]under grant[number 81101032][National Natural Science Foundation of China]under grant[number 81571628][Shanghai Municipal Commission of Health and Family Planning]under grant[number 201540048].
文摘Several viral infections are often associated with fetal brain structural anomalies,including white matter lesions,cerebellar hypoplasia,temporal lobe lesions,ventricular dilatation,intraventricular septa,ependymal cysts,and microcephaly,et al.Ultrasound(US)is the first modality of choice to evaluate fetal brain structural anomalies,however,Ultrasound is usually effected by maternal and fetal factors such as obesity,oligohydramnios and fetal head positions.Fetal MRI is not susceptible to the limitations as ultrasound with higher contrast resolution than prenatal ultrasound,directly visualize certain structures,such as developing brain parenchyma and further confirming US diagnosis and adding additional diagnostic information.This article reviews prenatal magnetic resonance imaging(MRI)diagnosis of fetal brain structural anomalies associated with viral infection.
基金supported by the Natural Science Foundation of Fujian Province of China,No.2015J01133the Professor Academic Development Foundation of Fujian Medical University of China,No.JS11003
文摘Neuro D plays a key regulatory effect on differentiation of neural stem cells into mature neurons in the brain.Thus,we assumed that electroacupuncture at Baihui（DU20） acupoint in newborn rats exposed to in utero fetal distress would influence expression of Neuro D.Electroacupuncture at Baihui was performed for 20 minutes on 3-day-old（Day 3） newborn Sprague-Dawley rats exposed to in utero fetal distress;electroacupuncture parameters consisted of sparse and dense waves at a frequency of 2–10 Hz.Real-time fluorescent quantitative PCR results demonstrated that m RNA expression of Neuro D,a molecule that indicates Neuro D,increased with prolonged time in brains of newborn rats,and peaked on Day 22.The level of m RNA expression was similar between Day 16 and Day 35.These findings suggest that electro acupuncture at Baihui acupoint could effectively increase m RNA expression of molecules involved in Neuro D in the brains of newborn rats exposed to in utero fetal distress.
基金supported by Research Funds of University of ukurova,Turkey
文摘Fetal cells can enter maternal blood during pregnancy but whether they can also cross the blood-brain barrier to enter the maternal brain remains poorly understood. Previous results suggest that fetal cells are summoned to repair damage to the mother＇s brain. If this is confirmed, it would open up new and safer avenues of treatment for brain damage caused by strokes and neural diseases. In this study, we aimed to investigate whether a baby＇s stem cells can enter the maternal brain during pregnancy. Deceased patients who had at least one male offspring and no history of abortion and blood transfusion were included in this study. DNA was extracted from brain tissue samples of deceased women using standard phenol-chloroform extraction and ethanol precipitation methods. Genomic DNA was screened by quantitative fluorescent-polymerase chain reaction amplification together with short tandem repeat markers specific to the Y chromosome, and 13, 18, 21 and X. Any foreign DNA residues that could be used to interpret the presence of fetal stem cells in the maternal brain were monitored. Results indicated that fetal stem cells can not cross the blood-brain barrier to enter the maternal brain.
基金supported by NIH grants R01NS97846,R01NS097846-02S1 and R01NS092876 awarded to MESShriners research grant SHC-85400 awarded to MESUSA Pennsylvania State Department grant Project 10:420491-04400-02 to ND。
文摘The pathology of fetal alcohol syndrome and the less severe fetal alcohol spectrum disorders includes brain dysmyelination.Recent studies have shed light on the molecular mechanisms underlying these white matter abnormalities.Rodent models of fetal alcohol syndrome and human studies have shown suppressed oligodendrocyte differentiation and apoptosis of oligodendrocyte precursor cells.Ethanol exposure led to reduced expression of myelin basic protein and delayed myelin basic protein expression in rat and mouse models of fetal alcohol syndrome and in human histopathological specimens.Several studies have reported increased expression of many chemokines in dysmyelinating disorders in central nervous system,including multiple sclerosis and fetal alcohol syndrome.Acute ethanol exposure reduced levels of the neuroprotective insulin-like growth factor-1 in fetal and maternal sheep and in human fetal brain tissues,while ethanol increased the expression of tumor necrosis factor α in mouse and human neurons.White matter lesions have been induced in the developing sheep brain by alcohol exposure in early gestation.Rat fetal alcohol syndrome models have shown reduced axon diameters,with thinner myelin sheaths,as well as reduced numbers of oligodendrocytes,which were also morphologically aberrant oligodendrocytes.Expressions of markers for mature myelination,including myelin basic protein,also were reduced.The accumulating knowledge concerning the mechanisms of ethanol-induced dysmyelination could lead to the development of strategies to prevent dysmyelination in children exposed to ethanol during fetal development.Future studies using fetal oligodendrocyte-and oligodendrocyte precursor cell-derived exosomes isolated from the mother's blood may identify biomarkers for fetal alcohol syndrome and even implicate epigenetic changes in early development that affect oligodendrocyte precursor cell and oligodendrocyte function in adulthood.By combining various imaging modalities with molecular studies,it may be possible to determine which fetuses are at risk and to intervene therapeutically early in the pregnancy.
文摘It is widely assumed that fetal ischemic brain injury during labor derives almost exclusively from severe, systemic hypoxemia with marked neonatal depression and acidemia. Severe asphyxia, however, is one of several causes of perinatal neurological injury and may not be the most common;most neonates diagnosed with hypoxic-ischemic encephalopathy do not have evidence of severe asphyxia. Sepsis, direct brain trauma, and drug or toxin exposure account for some cases, while mechanical forces of labor and delivery that increase fetal intracranial pressure sufficiently to impair brain perfusion may also contribute. Because of bony compliance and mobile suture lines, the fetal skull changes shape and redistributes cerebrospinal fluid during labor according to constraints imposed by contractions, and bony and soft tissue elements of the birth canal as the head descends. These accommodations, including the increase in intracranial pressure, are adaptive and necessary for efficient descent of the head while safeguarding cerebral blood flow. Autonomic reflexes mediated through central receptors normally provide ample protection of the brain from the considerable pressure exerted on the skull. On occasion, those forces, which are transmitted intracranially, may overcome the various adaptive anatomical, cardiovascular, metabolic, and neurological mechanisms that maintain cerebral perfusion and oxygen availability, resulting in ischemic brain injury. Accepting the notion of a potentially adverse impact of fetal head compression suggests that avoidance of excessive uterine activity and of relentless pushing without steady progress in descent may offer protection for the fetal brain during parturition. Excessive head compression should be considered in the differential diagnosis of ischemic encephalopathy.
基金funded by the National Natural Science Foundation of China,No.81170577
文摘From pregnancy to parturition, Sprague-Dawley rats were daily administered a low protein diet to establish a model of intrauterine growth restriction. From the 12th day of pregnancy, 300 mg/kg taurine was daily added to food until spontaneous delivery occurred. Brain tissues from normal neonatal rats at 6 hours after delivery, neonatal rats with intrauterine growth restriction, and neo- natal rats with intrauterine growth restriction undergoing taurine supplement were obtained for fur- ther experiments. The terminal deoxyribonucleotidyl transferase （TdT）-mediated biotin-16-dUTP nick-end labeling assay revealed that the number of apoptotic cells in the brain tissue of neonatal rats with intrauterine growth restriction significantly increased. Taurine supplement in pregnant rats reduced cell apoptosis in brain tissue from neonatal rats with intrauterine growth restriction. Immu- nohistochemical staining revealed that taurine supplement increased glial cell line-derived neuro- trophic factor expression and decreased caspase-3 expression in the cerebral cortex of intrauterine growth-restricted fetal rats. These results indicate that taurine supplement reduces cell apoptosis through the glial cell line-derived neurotrophic factor-caspase-3 signaling pathway, resulting in a protective effect on the intrauterine growth-restricted fetal rat brain.
基金supported by the Medical Scientific Research Foundation of Guangdong Province of China,No.A2015619
文摘Dexmedetomidine has significant neuroprotective effects. However, whether its protective effects can reduce neurotoxicity caused by isoflurane in fetal brain during the second trimester of pregnancy remains unclear. In this study, timed-pregnancy rats at gestational day 14 spontaneously inhaled 1.5% isoflurane for 4 hours, and were intraperitoneally injected with dexmedetomidine at dosages of 5, 10, 20, and 20 μg/kg 15 minutes before inhalation and after inhalation for 2 hours. Our results demonstrate that 4 hours after inhaling isoflurane, 20 μg/kg dexmedetomidine visibly mitigated isoflurane-induced neuronal apoptosis, reversed downregulation of brain-derived neurotrophic factor expression, and lessened decreased spatial learning and memory ability in adulthood in the fetal rats. Altogether, these findings indicate that dexmedetomidine can reduce neurodegeneration induced by isoflurane in fetal rats during the second trimester of pregnancy. Further, brain-derived neurotrophic factor participates in this process.
基金supported by the National Natural Science Foundation of China[81701350 and 31671252]the Health Technology Plan of Zhejiang Province[2023RC205].
文摘Maternal health during pregnancy has a direct impact on the risk and severity of neurodevelopmental disorders(NDDs)in the offspring,especially in the case of drug exposure.However,little progress has been made to assess the risk of drug exposure during pregnancy due to ethical constraints and drug use factors.We collected and manually curated sub-pathways and pathways(sub-/pathways)and drug information to propose an analytical framework for predicting drug candidates.This framework linked sub-/pathway activity and drug response scores derived from gene transcription data and was applied to human fetal brain development and six NDDs.Further,specific and pleiotropic sub-/pathways/drugs were identified using entropy,and sex bias was analyzed in conjunction with logistic regression and random forest models.We identified 19 disorder-associated and 256 regionally pleiotropic and specific candidate drugs that targeted risk sub-/pathways in NDDs,showing temporal or spatial changes across fetal development.Moreover,5443 differential drug-sub-/pathways exhibited sex-biased differences after filling in the gender labels.A user-friendly NDDP visualization website(https://ndd-lab.shinyapps.io/NDDP)was developed to allow researchers and clinicians to access and retrieve data easily.Our framework overcame data gaps and identified numerous pleiotropic and specific candidates across six disorders and fetal developmental trajectories.This could significantly contribute to drug discovery during pregnancy and can be applied to a wide range of traits.
文摘Objective: Mortality in FASD has not been well studied. In this paper we review published reports of mortality in FASD. Method: We searched using Pub Med for all years in all languages for reports of all-cause mortality associated with any FASD. Results: We located 26 papers reporting on 57 deaths. Cause of death was reported for 49/57 cases (86%). The two most prevalent potential causes of death were malformations of the heart (37 of 49 cases, 75.5%) which varied from atrial septal defect or patent ductus arteriosus to tetralogy of Fallot, hypoplastic left heart, aortic arch interruption, etc. and brain malformations(25 of 49, 51%) including microcephaly, hydrocephalus, porencephaly, agenesis/absence of the corpus callosum and semilobar holoprosencephaly. In several cases potential causal findings overlapped. The three most frequent other causes of death were sepsis (7 cases, 14.3%), kidney malformations (7 cases, 14.3%), and cancer (4 cases, 8.2%). Over half the deaths (30/55, 54.5%) occurred in the first year of life. Discussion: We found that congenital heart disease was the most common cause of death in people with FASD. This may be due to an ascertainment bias since many of the published studies were focused on congenital heart disease in FASD. We conclude that FASD is frequently undetected in mortality events and could be a common finding in infant, child, adolescent and adult mortality.
