Neurobiology of Disease最新文献

{"title":"The underlying role of pericyte-related cerebral lymphatic microcirculation dysfunction in cerebral small vessel disease","authors":"Tingting Cao ,&nbsp;Canhong Yang ,&nbsp;Jiafa Zhang ,&nbsp;Yuping Yan ,&nbsp;Zhefeng Chen ,&nbsp;Xiaojia Peng ,&nbsp;Chongshuang Xia ,&nbsp;Mika Pan ,&nbsp;Chun Zou ,&nbsp;Tianming Lü","doi":"10.1016/j.nbd.2025.107101","DOIUrl":"10.1016/j.nbd.2025.107101","url":null,"abstract":"<div><div>Cerebral small vessel disease (cSVD), a leading cause of stroke and cognitive impairment, is characterized by varied neuropathological features and neuroimaging findings, including enlarged perivascular spaces (EPVS), white matter hyperintensities (WMH), cerebral microbleeds (CMB), and cerebral subcortical ischemic lesions. The pathogenesis of cSVD has mainly been attributed to disruptions in blood circulation, such as arteriosclerosis, blood-brain barrier leakage, and reduced cerebral blood flow. However, many questions about the complex clinical and neuroimaging manifestations of cSVD remain. Growing evidence underscores the critical role of cerebral lymphatic system dysfunction in cSVD pathogenesis. The glymphatic system (GS) and intramural peri-arterial drainage (IPAD)—despite lacking the structure of lymphatic vessels in brain parenchyma, play critical roles in draining and clearing waste, akin to the cerebral lymphatic system. Pericytes, recognized as a key regulator of cerebral lymphatic microvascular function, have emerged as critical components of this system through their roles in with aquaporin-4 (AQP4) polarity and basement membrane remodeling. This review first provides a brief overview of cSVD, followed by a discussion of the role of pericytes in GS and IPAD, introducing the novel concept of pericyte-related cerebral lymphatic microcirculation. Finally, the involvement of pericyte-related cerebral lymphatic microcirculation in the pathophysiology of various subtypes of cSVD is explored. Elucidation of the mechanisms underlying cerebral lymphatic microcirculation disorder in cSVD expected to facilitate the development of therapeutic and preventive strategies for cSVD.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"216 ","pages":"Article 107101"},"PeriodicalIF":5.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of ABCC1 transporter ameliorates synaptic dysregulation in Tay-Sachs disease neuron","authors":"Yumeng Zhang ,&nbsp;Tadahiro Numakawa ,&nbsp;Ryutaro Kajihara ,&nbsp;Kiseok Lee ,&nbsp;Jing Pu ,&nbsp;Chisato Horita ,&nbsp;Jun Kido ,&nbsp;Muneaki Matsuo ,&nbsp;Takumi Era","doi":"10.1016/j.nbd.2025.107099","DOIUrl":"10.1016/j.nbd.2025.107099","url":null,"abstract":"<div><div>Tay-Sachs disease (TSD) is a congenital lysosomal storage disorder, caused by deficiency in the α-subunit of β-hexosaminidase A, leading to GM2 ganglioside accumulation in the central nervous system. Patients with TSD exhibit neural disturbances such as seizures, mental retardation; however, the molecular mechanisms behind neurological symptoms remain unclear. This study aimed to investigate altered synaptic function and explore treatment avenues for TSD. We observed the upregulation of postsynaptic receptors, abnormally elevated Ca²⁺ influx by neurotransmitter, and increased cell death under oxidative stress in TSD neurons. These abnormalities were associated with GM2 ganglioside accumulation. Additionally, we found that thiethylperazine, an approval drug for anti-emetics, mitigated GM2 ganglioside accumulation, potentially by activating the ATP-binding cassette subfamily C member 1 (ABCC1) transporter. This activation consequently improved the abnormal synaptic function. Our findings suggest that synaptic dysfunction is implicated in the neural disturbance in TSD, and highlight the ABCC1 transporter as a promising therapeutic target for this disease.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"216 ","pages":"Article 107099"},"PeriodicalIF":5.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thalamocortical dysrhythmia-related sleep spindle desynchronization in patients with tinnitus","authors":"Xiaoyu Bao ,&nbsp;Xueji Feng ,&nbsp;Di Chen ,&nbsp;Haiyun Huang ,&nbsp;Yuexin Cai ,&nbsp;Qiyun Huang ,&nbsp;Yuanqing Li","doi":"10.1016/j.nbd.2025.107081","DOIUrl":"10.1016/j.nbd.2025.107081","url":null,"abstract":"<div><div>Patients with tinnitus commonly suffer from sleep problems, and the underlying neural mechanisms remain unclear. Previous studies have focused primarily on the correlation between patients’ sleep structure and tinnitus, lacking exploration into the links between sleep problems and the underlying pathological mechanisms of tinnitus, such as thalamocortical dysrhythmia (TCD). Here, we present the first study on neural oscillatory patterns in patients with tinnitus during sleep spindles, a more precise subdivision of sleep that overlaps in neuropathological pathways with TCD. Sleep electroencephalogram (EEG) were recorded from 51 tinnitus participants and 51 healthy participants. During sleep spindles, patients with tinnitus exhibited a significant increase in 18–45 Hz and a stronger cross-frequency coupling, resembling the EEG abnormalities caused by TCD during wakefulness. With respect to spindle characteristics, tinnitus is linked to an increase in spindle quantity but a decrease in spindle root-mean-square and functional connectivity, suggesting that normal function of tinnitus spindles is impaired. Our findings indicated that neural oscillation dynamics related to TCD during sleep spindles serve as neural biomarkers for sleep disturbances in tinnitus participants. We demonstrate that the impact of the TCD pathological mechanism in tinnitus is not confined to the waking state but extends into the sleep stage as well, which advances our comprehension of the neural mechanisms underlying sleep-related problems in tinnitus.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"216 ","pages":"Article 107081"},"PeriodicalIF":5.6,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction notice to “Cytoplasmic gelsolin increases mitochondrial activity and reduces Aβ burden in a mouse model of Alzheimer's disease” [Neurobiology of Disease 36 (2009) 42–50]","authors":"Desiree Antequera ,&nbsp;Teo Vargas ,&nbsp;Cristina Ugalde ,&nbsp;Carlos Spuch ,&nbsp;Jose Antonio Molina ,&nbsp;Isidro Ferrer ,&nbsp;Felix Bermejo-Pareja ,&nbsp;Eva Carro","doi":"10.1016/j.nbd.2025.107088","DOIUrl":"10.1016/j.nbd.2025.107088","url":null,"abstract":"","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"215 ","pages":"Article 107088"},"PeriodicalIF":5.6,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145054849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Induced long-term potentiation improves synaptic stability and restores network function in ALS motor neurons","authors":"Anna M. Kollstrøm ,&nbsp;Marthe Bendiksvoll Grønlie ,&nbsp;Nicholas Christiansen ,&nbsp;Axel Sandvig ,&nbsp;Ioanna Sandvig","doi":"10.1016/j.nbd.2025.107077","DOIUrl":"10.1016/j.nbd.2025.107077","url":null,"abstract":"<div><div>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease causing progressive dysfunction and degeneration of upper and lower motor neurons. An increasing body of evidence has identified synaptic alterations in patients and experimental models of ALS. Importantly, these have been associated with functional impairments in motor neuron networks, suggesting that synaptic impairments are early events in the disease cascade resulting in functional compensatory reconfigurations. The synapse may therefore represent a disease-modifying target to delay disease progression. In this study, we aimed to stabilize synapses and modify structural connectivity to restore network balance in ALS patient-derived motor neuron networks. To this end, we blocked the potassium channels using tetraethylammonium (TEA) which has been shown to induce chemical long-term potentiation (cLTP). The unperturbed ALS patient-derived motor neuron networks developed clear signs of subtle network dysfunction, including increased firing rate and bursting, and accompanying structural abnormalities. These features were partially restored by temporarily blocking the potassium channels. Specifically, the TEA-treated ALS networks were characterized by a reduction in aberrant branching and stabilization of dendritic spines, alongside a temporary reduction in firing rate and bursting. Furthermore, protein expression assays revealed restoration of dysregulated molecular pathways, including protein synthesis and metabolic pathways, and upregulation of pathways involved in synapse organization in the TEA-treated ALS networks. This is one of the first studies to integrate synaptic potentiation, proteomics, and functional network analysis of human ALS motor neurons. Collectively, these findings improve our understanding of the association between synaptic impairments and functional alterations in ALS, and demonstrate the therapeutic potential of targeting neuronal excitability and plasticity to promote network balance.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"216 ","pages":"Article 107077"},"PeriodicalIF":5.6,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction Notice to “Cerebrospinal fluid of Alzheimer patients promotes β-amyloid fibril formation in vitro” [Neurobiology of Disease 20 (2005) 233–240]","authors":"Kenjiro Ono ,&nbsp;Moeko Noguchi ,&nbsp;Yasuko Matsumoto ,&nbsp;Daisuke Yanase ,&nbsp;Kazuo Iwasa ,&nbsp;Hironobu Naiki ,&nbsp;Masahito Yamada","doi":"10.1016/j.nbd.2025.107087","DOIUrl":"10.1016/j.nbd.2025.107087","url":null,"abstract":"","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"215 ","pages":"Article 107087"},"PeriodicalIF":5.6,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145054831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered microglial polarization reduces demyelination in cerebellar slices treated with serum from CD20-depleted multiple sclerosis patients","authors":"Lara-Jasmin Schröder ,&nbsp;Franz Felix Konen ,&nbsp;Hauke Thiesler ,&nbsp;Viktoria Gudi ,&nbsp;Herbert Hildebrandt ,&nbsp;Philipp Schwenkenbecher ,&nbsp;Thomas Skripuletz","doi":"10.1016/j.nbd.2025.107096","DOIUrl":"10.1016/j.nbd.2025.107096","url":null,"abstract":"<div><h3>Background</h3><div>Ofatumumab (OFT) is a recently developed fully human anti-CD20 monoclonal antibody approved for treating relapsing multiple sclerosis (MS), targeting B-cells and thereby limiting antibody production. Admittedly, its impact on central nervous system (CNS) demyelination and glial cells remains underexplored.</div></div><div><h3>Methods</h3><div>Serum samples from MS patients before and after a 6-month OFT treatment were analyzed regarding cytokines and their impact on BV-2 microglia activation. These sera were then used in an acute demyelination model applying lysophosphatidylcholine (LPC)-induced murine cerebellar slice cultures to assess effects on myelination and glial modulation.</div></div><div><h3>Results</h3><div>OFT treatment resulted in a decrease in proinflammatory cytokines and an increase in anti-inflammatory cytokines in patient sera, indicating a reduction in inflammation. Partially, inflammatory activation appears to be caused by serum-inherent TLR4 ligands which were absent in 6-month OFT sera, as evaluated by nitric oxide determination in BV-2 microglia. Serum from 6-month OFT treatment patients indirectly protected against myelin disintegration and supported oligodendrocyte survival during LPC-induced demyelination. This protection correlated with reduced astrogliosis and a shift in microglial polarization towards an anti-inflammatory phenotype, characterized by decreased nitric oxide and cytokine production, and increased arginase-1 and IL-10 levels.</div></div><div><h3>Conclusion</h3><div>Depletion of CD20 positive cells via OFT appears to indirectly prevent demyelination by modulating microglial polarization. This is linked to reduced serum cytokines and absence of serum-inherent TLR4 ligands post-treatment, suggesting a potential peripheral immunomodulation-mediated protective mechanism impacting CNS immune responses. These findings underscore the need to investigate how therapies targeting peripheral immune cells can also influence CNS immune mechanisms.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"215 ","pages":"Article 107096"},"PeriodicalIF":5.6,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145045004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebrospinal amino acid profiling in a large cohort of neuropediatric patients with epilepsy","authors":"Helena Rodriguez-Gonzalez ,&nbsp;Laia Nou-Fontanet ,&nbsp;Aida Ormazabal ,&nbsp;Mercedes Casado ,&nbsp;Ángela Arias ,&nbsp;Leticia Pias-Peleteiro ,&nbsp;Ana Gutierrez ,&nbsp;Alexandre Perera-Lluna ,&nbsp;Angels Garcia-Cazorla ,&nbsp;Carmen Fons ,&nbsp;Rafael Artuch","doi":"10.1016/j.nbd.2025.107098","DOIUrl":"10.1016/j.nbd.2025.107098","url":null,"abstract":"<div><div>This study addresses challenges in cerebrospinal fluid (CSF) amino acid profiling in pediatric neurological disorders by establishing age-continuous reference intervals. It examines amino acid variations in epilepsy of different etiologies and evaluates the effects of antiseizure medications (ASMs), resolving inconsistencies in previous research. We retrospectively analyzed 410 CSF samples from pediatric patients (201 with epilepsy). Reference intervals were established using linear regression, adjusting for age and sex as confounders. Statistical analysis of age-normalized data included tests to assess the relationship between clinical features and altered or normal amino acid levels, multiple regression models evaluating the effects of ASMs on CSF amino acid levels, and hierarchical clustering for pattern identification. Age significantly influenced CSF amino acid levels, with higher concentrations observed in neonates, except for aspartic acid and arginine. Sex was not a significant predictor. Over 90 % of patients with epilepsy had normal levels for most amino acids, except for glutamine, which was more frequently elevated in epilepsy. Valproate and GABAA receptor agonists were linked to elevated glutamine, while vigabatrin therapy was associated with increased levels of ornithine, leucine, and isoleucine. Hierarchical clustering identified a subcluster with elevated essential amino acid levels, predominantly comprising patients with generalized seizures or status epilepticus. This study establishes new CSF amino acid reference intervals for pediatric patients and finds no significant associations between individual amino acid levels and epilepsy-related clinical features. However, a subgroup with high essential amino acid levels, primarily associated with generalized epilepsy, suggests potential links to generalized epileptogenic discharges and blood–brain barrier disruption.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"216 ","pages":"Article 107098"},"PeriodicalIF":5.6,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145054799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences of synaptic plasticity and microglial remodeling in the dorsal hippocampus following trigeminal nerve injury in mice","authors":"Manindra Nath Tiwari,&nbsp;Lauren Paik,&nbsp;Fernando da Silva Fiorin ,&nbsp;Man-Kyo Chung","doi":"10.1016/j.nbd.2025.107097","DOIUrl":"10.1016/j.nbd.2025.107097","url":null,"abstract":"<div><div>Peripheral nerve injury patients have chronic pain as well as poor memory and cognitive functioning that is associated with hippocampal abnormalities. Despite sex-dependent changes in the hippocampus of patients with chronic pain, detailed sex differences in hippocampal plasticity after peripheral nerve injury are not well known. In mice with infraorbital nerve chronic constriction injury (ION-CCI), we found complex sex differences in the dorsal hippocampus (dHC). ION-CCI suppressed population spikes amplitude and long-term potentiation (LTP) in the dHC compared to sham group, which was consistent in females but not males. The field excitatory postsynaptic potential was comparable between sexes in the sham group, and ION-CCI suppressed it in both sexes. Short-term facilitation after paired-pulse protocol was also comparable between the sexes in the sham group but was only suppressed in males with ION-CCI. While microglial numbers in the dHC were comparable between the sexes, the proportion of hyper-ramified microglia was higher in males in the sham group. ION-CCI increased the total number of microglia in both sexes; however, the proportion of hyper-ramified microglia was increased by ION-CCI in females only. In novel object recognition tests, female mice exhibited better object recognition memory than males in the sham group, which was impaired by ION-CCI. Taken together, these results suggest that female mice exhibit stronger object recognition in the uninjured condition, which may be related to stronger hippocampal synaptic functions and potentiation. Furthermore, trigeminal nerve injury may produce a greater effect on synaptic functions and plasticity, along with cognitive deficits, in females.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"215 ","pages":"Article 107097"},"PeriodicalIF":5.6,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145041002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibiting EPAC1 improves brain edema and neurological outcomes by regulating AQP4 polarization after intracerebral hemorrhage","authors":"Jingjing Chen ,&nbsp;Guannan Jiang ,&nbsp;Xiaoqing Hu ,&nbsp;Lei Bai ,&nbsp;Haiying Li ,&nbsp;Ximing Wang ,&nbsp;Xiang Li Sr","doi":"10.1016/j.nbd.2025.107095","DOIUrl":"10.1016/j.nbd.2025.107095","url":null,"abstract":"<div><div>Intracerebral hemorrhage (ICH) is a severe cerebrovascular event associated with high mortality and disability, primarily due to perihematomal edema (PHE). Aquaporin-4 (AQP4) polarization plays a crucial role in PHE development; however, effective therapeutic strategies remain elusive. This study investigates the mechanisms regulating AQP4 polarization and brain edema in a murine ICH model, with autologous blood injected into the striatum of adult C57BL/6 J mice. Three approaches were employed: (1) a time-course analysis (0, 24, 48, and 72 h post-ICH) to assess brain edema and AQP4 localization via magnetic resonance imaging (MRI), electron microscopy, and immunofluorescence; (2) pharmacological modulation of EPAC1 using an inhibitor (ESI-09, 10 mg/kg, intraperitoneal) and an activator (8-CPT, 20 μM, intravenous) to evaluate its role in AQP4 polarization; (3) lentiviral knockdown of AQP4 to investigate its interaction with EPAC1. Results showed that AQP4 underwent partial depolarization, characterized by reduced AQP4-M23 expression and decreased colocalization with CD31, coinciding with significant brain edema at 72 h post-ICH. Proteomic and network analyses, utilizing AlphaFold for protein structure prediction, identified exchange protein directly activated by cyclic adenosine monophosphate 1 (EPAC1) as a key regulator of AQP4 polarization, with its interaction with AQP4 markedly reduced following ICH. Pharmacological inhibition of EPAC1 with ESI-09 mitigated AQP4 depolarization, whereas activation with 8-CPT exacerbated it. Moreover, AQP4 knockdown attenuated the protective effects of EPAC1 inhibition, leading to aggravated brain edema and worsened neurological deficits. These findings suggest that targeting EPAC1-mediated AQP4 polarization may provide a novel therapeutic strategy for ICH.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"215 ","pages":"Article 107095"},"PeriodicalIF":5.6,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145041013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}