Developmental Neuroscience最新文献

{"title":"Synaptic pruning by microglia: Lessons from genetic studies in mice.","authors":"Junia Lara de Deus,Oluwaseun Samuel Faborode,Sayan Nandi","doi":"10.1159/000541379","DOIUrl":"https://doi.org/10.1159/000541379","url":null,"abstract":"BACKGROUNDNeural circuits are subjected to refinement throughout life. The dynamic addition and loss of synapses (pruning) are necessary for maturation of neural circuits and synaptic plasticity. Due to their phagocytic nature, microglia have been considered as the primary mediators of synaptic pruning. Synaptic pruning can strengthen an active synapse by removing excess weaker synapses during development. Inappropriate synaptic pruning can often influence a disease outcome or an injury response.SUMMARYThis review offers a focused discussion on microglial roles in synaptic pruning, based on the evidence gathered from genetic manipulations in mice. Genetically-labeled microglia and synapses often allow assessment of their interactions in real time. Further manipulations involving synaptically-localized molecules, neuronally- or glial-derived diffusible factors, and their respective cognate receptors in microglia, provide critical evidence in support of a direct role of microglia in synaptic pruning.KEY MESSAGEWe discuss microglial contact-dependent \"eat-me\", \"don't-eat-me\" and \"find-me\" signals, as well as recently identified non-contact pruning, under the contexts of neural circuit, brain region, developmental window, and an injury or a disease state.","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The association between ventricle ratio in preterm infants and motor developmental delay.","authors":"Hyun Iee Shin, Na Mi Lee, Sun Mi Kim, Hyunchan Hwang, Gangta Choi, Doug Hyun Han, Don-Kyu Kim","doi":"10.1159/000540754","DOIUrl":"https://doi.org/10.1159/000540754","url":null,"abstract":"<p><p>Introduction Early prediction and timely intervention are particularly essential for high-risk preterm infants. Brain magnetic resonance imaging (BMRI) is frequently used alongside functional evaluations to improve predictions of developmental outcomes. This study aimed to assess voxel-based brain volumetry in extremely preterm infants using BMRI at term equivalent age (TEA) and investigate its association with developmental outcomes. Methods From March 2016 to December 2019, high-risk preterm infants (birth weight &lt; 1500g or gestational age &lt; 32 weeks) with BMRI at TEA and follow-up developmental data assessed by Bayley-III were included. For BMRI volumetry, manual tracing and segmentation were performed on T1-weighted scans, and after smoothing, voxels were calculated for each brain segment. Forty-seven subjects were enrolled and categorized into typical/delayed motor groups Results Results revealed a significant difference in ventricle size and ventricle ratio in BMRI at TEA between the groups. Even after controlling for other factors that could influence developmental outcomes, ventricle ratio emerged as a robust, single predictor for future motor development. Conclusion This study suggests the potential clinical utility of BMRI volumetry in predicting motor development outcomes.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective Effects of Early Neonatal Methylxanthine Treatment on Cognitive and Language Outcomes in Premature Infants with and without High-Risk Perinatal Factors.","authors":"Ruth M McLeod, Ted S Rosenkrantz, R Holly Fitch","doi":"10.1159/000540540","DOIUrl":"10.1159/000540540","url":null,"abstract":"<p><strong>Introduction: </strong>Caffeine and theophylline are methylxanthines and nonselective adenosine antagonists commonly used to treat apnea of prematurity. Both human and animal data suggest that xanthines also have clinically important long-term neuroprotective effects in the presence of inflammation in the perinatal period as seen following hypoxic-ischemic brain insults. Moreover, these protective effects appear to be more robust when administered shortly (&lt;48 h) after preterm birth.</p><p><strong>Method: </strong>To evaluate the importance of the postdelivery therapeutic window, we collected and analyzed medical data from preterm infants meeting criteria (23-30 weeks' gestational age [GA]), born at the University of Connecticut Health Center (UCHC), and cared for at the UCHC/Connecticut Children's Medical Center (CCMC) NICU from 1991 to 2017 (n = 858). Eighteen-month follow-up data included cognitive and language scores from the Neonatal Neurodevelopmental Follow-Up Clinic records, with a retention of 81% of subjects (n = 696). Differences were analyzed via multivariate ANOVA and ANCOVA.</p><p><strong>Results: </strong>Analyses showed that infants who received xanthine treatment within the first 48 h after preterm birth showed significantly better 18-month behavioral outcomes than those treated later than 48 h, despite a lack of a priori differences in GA, birth, or length of stay. The positive effect of early xanthine therapy was particularly robust for infants exposed prenatally to the inflammatory conditions of chorioamnionitis and/or preeclampsia.</p><p><strong>Conclusions: </strong>Current findings are consistent with human and animal data, showing that caffeine exerts protective effects, at least in part via attenuation of inflammation. Results add to the evidence supporting routine immediate prophylactic neuroprotective xanthine therapy (i.e., caffeine) in preterm infants. Findings also add important new evidence of the augmented value of caffeine for infants with inflammatory exposure due to mothers with preeclampsia or chorioamnionitis.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dendritic Morphology of Developing Hippocampal Neurons in Cyp11a1 Null Mice.","authors":"Hao-Hua Jiang, Tzu-Hsuan Wu, Li-Jen Lee, Jui-Chen Lee, Bon-Chu Chung, Feng-Ming Yang, Meng-Chun Hu","doi":"10.1159/000540106","DOIUrl":"10.1159/000540106","url":null,"abstract":"<p><strong>Introduction: </strong>Neurosteroids have a variety of neurological functions, such as neurite growth, neuroprotection, myelination, and neurogenesis. P450scc, encoded by CYP11A1 gene, is the cholesterol side chain cleavage enzyme that catalyzes the first and rate-limiting step in steroidogenesis. In this study, we examine the dendritic morphology in developing hippocampal neurons of Cyp11a1 null mice at P15, a critical period for synapse formation and maturation.</p><p><strong>Methods: </strong>Knockout mice were maintained until P15 with hormone administration. The Golgi-Cox method stained CA1 and CA3 pyramidal neurons in the hippocampus to reveal dendritic morphology.</p><p><strong>Results: </strong>We demonstrated that Cyp11a1 null mice usually die within 7 days after birth and thus collected brain samples at postnatal day 5 (P5) for examination. There was significant shrinkage of dendrite size and diminishment of dendritic branching in CA1 and CA3 pyramidal neurons in the hippocampus of Cyp11a1 null mice, suggesting a developmental delay. We wonder if this delay may catch up later in life. Since the age of P15 is a critical period for synapse formation and maturation, the Cyp11a1 null mice were rescued by receiving hormone administration until P15 that the dendritic morphology in the developing hippocampal neurons could be examined. The results indicated that the total dendritic length, the number of dendritic branches, as well as dendritic arborization in the CA1 and CA3 pyramidal neurons are significantly decreased in P15 knockout mice when compared to the wild type. The spine densities were also significantly decreased. In addition, the Western blot analysis revealed decreased PSD-95 expression levels in the knockout mice compared to the wild type at P15.</p><p><strong>Conclusion: </strong>These results suggested that Cyp11a1 deficiency impairs the dendritic structures in the developing hippocampal pyramidal neurons.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141494121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripuberty Is a Sensitive Period for Prefrontal Parvalbumin Interneuron Activity to Impact Adult Cognitive Flexibility.","authors":"Gabriella M Sahyoun, Trang Dao Do, Amanda Anqueira-Gonzàlez, Ava Hornblass, Sarah E Canetta","doi":"10.1159/000539584","DOIUrl":"10.1159/000539584","url":null,"abstract":"<p><strong>Introduction: </strong>Developmental windows in which experiences can elicit long-lasting effects on brain circuitry and behavior are called \"sensitive periods\" and reflect a state of heightened plasticity. The classic example of a sensitive period comes from studies of sensory systems, like the visual system, where early visual experience is required for normal wiring of primary visual cortex and proper visual functioning. At a mechanistic level, loss of incoming visual input results in a decrease in activity in thalamocortical neurons representing the affected eye, resulting in an activity-dependent reduction in the representation of those inputs in the visual cortex and loss of visual perception in that eye. While associative cortical regions like the medial prefrontal cortex (mPFC) do not receive direct sensory input, recent findings demonstrate that changes in activity levels experienced by this region during defined windows in early development may also result in long-lasting changes in prefrontal cortical circuitry, network function, and behavior. For example, we recently demonstrated that decreasing the activity of mPFC parvalbumin-expressing (PV) interneurons during a period of time encompassing peripuberty (postnatal day P14) to adolescence (P50) led to a long-lasting decrease in their functional inhibition of pyramidal cells, as well as impairments in cognitive flexibility. While the effects of manipulating mPFC PV interneuron activity were selective to development, and not adulthood, the exact timing of the sensitive period for this manipulation remains unknown.</p><p><strong>Methods: </strong>To refine the sensitive period in which inhibiting mPFC PV cell activity can lead to persistent effects on prefrontal functioning, we used a chemogenetic approach to restrict our inhibition of mPFC PV activity to two distinct windows: (1) peripuberty (P14-P32) and (2) early adolescence (P33-P50). We then investigated adult behavior after P90. In parallel, we performed histological analysis of molecular markers associated with sensitive period onset and offset in visual cortex, to define the onset and offset of peak-sensitive period plasticity in the mPFC.</p><p><strong>Results: </strong>We found that inhibition of mPFC PV interneurons in peripuberty (P14-P32), but not adolescence (P33-P50), led to an impairment in set-shifting behavior in adulthood manifest as an increase in trials to reach criterion performance and errors. Consistent with a pubertal onset of sensitive period plasticity in the PFC, we found that histological markers of sensitive period onset and offset also demarcated P14 and P35, respectively. The time course of expression of these markers was similar in visual cortex.</p><p><strong>Conclusion: </strong>Both lines of research converge on the peripubertal period (P14-P32) as one of heightened sensitive period plasticity in the mPFC. Further, our direct comparison of markers of sensitive period plasticity across the pr","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural and Functional Effects of C5aR1 Antagonism in a Rat Model of Neonatal Hypoxic-Ischemic Encephalopathy.","authors":"Angela Saadat, Haree Pallera, Frank Lattanzio, Daley Owens, Amy Gaines, Sai Susmitha Ravi, Tushar Shah","doi":"10.1159/000539506","DOIUrl":"10.1159/000539506","url":null,"abstract":"<p><strong>Introduction: </strong>The complement response activates upon reperfusion in neonatal hypoxic-ischemic encephalopathy (HIE) and contributes to excessive neuroinflammation and worse outcomes. C5a is a powerful anaphylatoxin central to each of the complement pathways, and its engagement with C5aR1 is directly tied to brain injury and neuronal death. Reasoning C5aR1 antagonism can decrease excessive neuroinflammation and thereby improve neurological and functional outcomes, we tested this hypothesis in a rat model of HIE with PMX205, a small molecule that inhibits C5a-C5aR1 interaction.</p><p><strong>Methods: </strong>Term-equivalent pups (P10-12) were subjected to mild-moderate HIE by Vannucci's method and treated with PMX205. We compared motor and cognitive outcomes with two behavioral tests each (food handling and accelerod; novel object recognition [NOR] and open field) to improve the accuracy of our conclusions.</p><p><strong>Results: </strong>Improvements were observed in fine motor function, balance, and exploratory behaviors, but little to no improvement in recognition memory and gross motor function. Lesion area and histological assessments showed robust cortical neuroprotection from treatment but persistent injury to the CA1 region of the hippocampus. Better structural and functional outcomes were seen within 1 day of treatment, suggesting C5aR1 antagonism beyond the latent injury phase may impair recovery. In a dose-response experiment, cerebral area loss from injury was improved only in female rats, suggesting underlying sexual dimorphisms in the complement response.</p><p><strong>Conclusion: </strong>These results demonstrate proof-of-concept for targeting C5aR1 signaling in neonatal HIE with PMX205 and underscore the role of sex in hypoxic-ischemic injury.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Neurologic Consequences following Fetal Growth Restriction: The Impact on Brain Reserve.","authors":"Divyen K Shah, Susana Pereira, Gregory A Lodygensky","doi":"10.1159/000539266","DOIUrl":"10.1159/000539266","url":null,"abstract":"<p><strong>Background: </strong>Fetal growth restriction (FGR) corresponds to the fetus's inability to achieve an adequate weight gain based on genetic potential and gestational age. It is an important cause of morbidity and mortality.</p><p><strong>Summary: </strong>In this review, we address the challenges of diagnosis and classification of FGR. We review how chronic fetal hypoxia impacts brain development. We describe recent advances on placental and fetal brain imaging using magnetic resonance imaging and how they offer new noninvasive means to study growth restriction in humans. We go on to review the impact of FGR on brain integrity in the neonatal period, later childhood, and adulthood and review available therapies.</p><p><strong>Key messages: </strong>FGR consequences are not limited to the perinatal period. We hypothesize that impaired brain reserve, as defined by structure and size, may predict some concerning epidemiological data of impaired cognitive outcomes and dementia with aging in this group of patients.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140917406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beta Spectral Power during Passive Listening in Preschool Children with Specific Language Impairment.","authors":"Saška Fatić, Nina Stanojević, Ljiljana Jeličić, Ružica Bilibajkić, Maša Marisavljević, Slavica Maksimović, Aleksandar Gavrilović, Miško Subotić","doi":"10.1159/000539135","DOIUrl":"10.1159/000539135","url":null,"abstract":"<p><strong>Introduction: </strong>Children with specific language impairment (SLI) have difficulties in different speech and language domains. Electrophysiological studies have documented that auditory processing in children with SLI is atypical and probably caused by delayed and abnormal auditory maturation. During the resting state, or different auditory tasks, children with SLI show low or high beta spectral power, which could be a clinical correlate for investigating brain rhythms.</p><p><strong>Methods: </strong>The aim of this study was to examine the electrophysiological cortical activity of the beta rhythm while listening to words and nonwords in children with SLI in comparison to typical development (TD) children. The participants were 50 children with SLI, aged 4 and 5 years, and 50 age matched TD children. The children were divided into two subgroups according to age: (1) children 4 years of age; (2) children 5 years of age.</p><p><strong>Results: </strong>The older group differed from the younger group in beta auditory processing, with increased values of beta spectral power in the right frontal, temporal, and parietal regions. In addition, children with SLI have higher beta spectral power than TD children in the bilateral temporal regions.</p><p><strong>Conclusion: </strong>Complex beta auditory activation in TD and SLI children indicates the presence of early changes in functional brain connectivity.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140899631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical Milestones in MECP2 Gene Transfer for Treating Rett Syndrome.","authors":"Indumathy Jagadeeswaran, Jiyoung Oh, Sarah E Sinnett","doi":"10.1159/000539267","DOIUrl":"10.1159/000539267","url":null,"abstract":"<p><strong>Background: </strong>Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the transcriptional regulator methyl-CpG-binding protein 2 (MeCP2). After gene transfer in mice, exogenous MeCP2 expression must be regulated to avoid dose-dependent toxicity.</p><p><strong>Summary: </strong>The preclinical gene therapy literature for treating RTT illustrates a duly diligent progression that begins with proof-of-concept studies and advances toward the development of safer, regulated MECP2 viral genome designs. This design progression was partly achieved through international collaborative studies. In 2023, clinicians administered investigational gene therapies for RTT to patients a decade after the first preclinical gene therapy publications for RTT (clinical trial numbers NCT05606614 and NCT05898620). As clinicians take on a more prominent role in MECP2 gene therapy research, preclinical researchers may continue to test more nuanced hypotheses regarding the safety, efficacy, and mechanism of MECP2 gene transfer.</p><p><strong>Key message: </strong>This review summarizes the history of preclinical MECP2 gene transfer for treating RTT and acknowledges major contributions among colleagues in the field. The first clinical injections are a shared milestone.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140899633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinguishing Laterality in Brain Injury in Rabbit Fetal Magnetic Resonance Imaging Using Novel Volume Rendering Techniques.","authors":"Gaurav Ambwani, Zhongjie Shi, Kehuan Luo, Jeong-Won Jeong, Sidhartha Tan","doi":"10.1159/000539212","DOIUrl":"10.1159/000539212","url":null,"abstract":"<p><strong>Introduction: </strong>Our laboratory has been exploring the MRI detection of fetal brain injury, which previously provided a prognostic biomarker for newborn hypertonia in an animal model of cerebral palsy (CP). The biomarker relies on distinct patterns of diffusion-weighted imaging-defined apparent diffusion coefficient (ADC) in fetal brains during uterine hypoxia-ischemia (H-I). Despite the challenges posed by small brains and tissue acquisition, our objective was to differentiate between left and right brain ADC changes.</p><p><strong>Methods: </strong>A novel aspect involved utilizing three-dimensional rendering techniques to refine ADC measurements within spheroids encompassing fetal brain tissue. 25-day gestation age of rabbit fetuses underwent global hypoxia due to maternal uterine ischemia.</p><p><strong>Results: </strong>Successful differentiation of left and right brain regions was achieved in 28% of the fetal brains. Ordinal analysis revealed predominantly higher ADC on the left side compared to the right at baseline and across the entire time series. During H-I and reperfusion-reoxygenation, the right side exhibited a favored percentage change. Among these fetal brains, 73% exhibited the ADC pattern predictive of hypertonia. No significant differences between left and right sides were observed in patterns predicting hypertonia, except for one timepoint during H-I. This study also highlights a balance between left-sided and right-sided alterations within the population.</p><p><strong>Conclusion: </strong>This study emphasizes the importance of investigating laterality and asymmetric hemispheric lesions for early diagnosis of brain injury, leading to CP. The technological limitations in obtaining a clear picture of the entire fetal brain for every fetus mirror the challenges encountered in human studies.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140863995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}