Developmental Neuroscience最新文献

{"title":"Erratum.","authors":"","doi":"10.1159/000545780","DOIUrl":"10.1159/000545780","url":null,"abstract":"","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1"},"PeriodicalIF":2.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum.","authors":"","doi":"10.1159/000545629","DOIUrl":"https://doi.org/10.1159/000545629","url":null,"abstract":"","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1"},"PeriodicalIF":2.3,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004325","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":"Pediatric post-infectious neuroinflammatory syndromes come to the fore.","authors":"Samuel J Pleasure","doi":"10.1159/000546082","DOIUrl":"https://doi.org/10.1159/000546082","url":null,"abstract":"<p><p>n/a.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-4"},"PeriodicalIF":2.3,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037757","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":"A Bioinformatic Investigation into a Unique Human FOXM1 Exon Variant and its Relevance to Gyrencephaly.","authors":"Mikaela Barresi, Alice Johnstone, Mary Tolcos","doi":"10.1159/000545713","DOIUrl":"https://doi.org/10.1159/000545713","url":null,"abstract":"<p><p>Gyrification is a shared phenotype of brain development across many species. The identification of human- and primate-specific genes is a topic of great research interest to uncover the genetic mechanisms that drive human gyrification. Here we investigated a human transcript variant of FOXM1 with a unique ninth exon proposed to have a crucial role in primate gyrification. Through comprehensive bioinformatic analyses utilising available deposited sequencing data, we aimed to determine the degree of conservation of human FOXM1 exon 9 across a wide range of species, with a particular focus on gyrencephalic primates. Surprisingly, our results revealed that the exon is only partially detected in four other primates challenging its presumed conservation in humans, apes, and other primates. Furthermore, we aimed to determine the degree of conservation of the remaining regions of FOXM1 across a subset of gyrencephalic and lissencephalic species. The remaining regions of FOXM1 had a remarkably high level of conservation, and given its role in regulating proliferation and differentiation, the results suggested that FOXM1 may be required for early brain development across all species. However, the sporadic presence of the exon 9 sequence even in other gyrencephalic primates raises questions about its indispensability in the process of gyrification. Therefore, we conclude that the FOXM1 transcript variant comprising the exon 9 sequence in its entirety could be more appropriately reclassified as a human-specific cortical folding variant not found in other species. This research lays the foundation for further investigating the role of FOXM1 exon 9 in human gyrification and brain development.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-13"},"PeriodicalIF":2.3,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058917","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":"Defining clinical course of patients evaluated for pediatric acute-onset neuropsychiatric syndrome (PANS): phenotypic classification based on 10 years of clinical data.","authors":"Erin E Masterson, Kate Miles, Noelle Schlenk, Cindy Manko, Meiqian Ma, Bahare Farhadian, Kiki Chang, Melissa Silverman, Margo Thienemann, Jennifer Frankovich","doi":"10.1159/000545598","DOIUrl":"https://doi.org/10.1159/000545598","url":null,"abstract":"<p><strong>Objective: </strong>Establishing clear and standardized terminology regarding disease state and course is crucial for enhancing communication, research, and treatment decisions, particularly when there are no clearly identified biological markers, as in the case of pediatric acute-onset neuropsychiatric syndrome (PANS). We aim to propose terminology for assessing disease state and classifying long-term clinical courses in individuals evaluated for PANS, advancing standardization in clinical care and research.</p><p><strong>Methods: </strong>We drew upon clinical expertise, insights from similar conditions, and a decade of longitudinal clinical data from the Stanford University Immune Behavioral Health (IBH) Clinic to devise terminology for characterizing patient status and clinical progression among patients evaluated for PANS. Utilizing parent- and clinician-reported data spanning from 2012 to 2023, we constructed a comprehensive dataset documenting patients' disease trajectory from initial flare to latest clinical encounter, encompassing intervening recovery periods. This allowed us to apply the proposed terminology to the IBH Clinic patient cohort, offering a detailed phenotypic analysis of PANS flare and clinical courses.</p><p><strong>Results: </strong>We analyzed 264 patients evaluated for PANS at the IBH Clinic and stratified them based on whether they met PANS criteria at initial flare (51%), after initial flare (24%), or had not met criteria at the time of analysis (25%). The average age at the initial flare ranged from 6.1-8.3 years across these patient sub-groups. Among patients with PANS, the average isolated flare lasted 3.7-4.1 months and 95% of flares resolved within one year. Five years after initial flare, most (77%) patients with PANS had had multiple flares, and nearly half (43%) had experienced a flare that lasted > 12 months, approximately half of which occurred at the initial flare.</p><p><strong>Conclusions: </strong>Patients evaluated for PANS at the IBH Clinic showed diverse clinical presentations and illness courses over the long term, with most experiencing a relapsing-remitting clinical course but some exhibiting persistent symptoms. Many experienced neuropsychiatric flares before meeting PANS classification criteria. This underscores the importance of clinicians being vigilant for new neuropsychiatric symptoms in pediatric patients, even if they do not immediately meet PANS criteria. Based on these data, we propose terms and definitions for characterizing patient status, flares, and clinical course, which we hope the clinical and research communities will build on and refine.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-33"},"PeriodicalIF":2.3,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796897","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":"A Pilot Study on Dynamic Multimodal Neuromonitoring for Predicting Neurodevelopmental Outcomes in Neonatal Hypoxic-Ischemic Encephalopathy.","authors":"Srinivas Kota, Lynn Bitar, Pollieanna Sepulveda, Soheila Norasteh, Hanli Liu, Lina F Chalak","doi":"10.1159/000545599","DOIUrl":"10.1159/000545599","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Multimodal neuromonitoring at the bedside is essential for understanding the pathophysiological mechanisms of brain injury and neurodevelopmental outcomes associated with neonatal hypoxic-ischemic encephalopathy (HIE). While previous research has focused on single modality neuromonitoring biomarkers to predict neurodevelopmental impairment (NDI) at 2 years of age, there remains significant gap in exploring the potential of multimodal physiological signal biomarkers to improve predictive accuracy. This study aimed to evaluate multimodal quantitative neuromonitoring biomarkers within the first day of life to improve prediction of NDI.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This prospective cohort study enrolled newborns (≥36 weeks) diagnosed with HIE at Parkland Hospital in Dallas, TX. A Sarnat examination was performed to determine the severity of HIE within the first 6 h of life, and the Total Sarnat Score (TSS) was calculated. Newborns with moderate and severe HIE received therapeutic hypothermia (TH). Neuronal noninvasive biomarkers including electroencephalogram (EEG) delta power (DP, 0.5-4 Hz) and neurovascular coupling (NVC), calculated as wavelet coherence between amplitude-integrated EEG and cerebral tissue oxygen saturation (SctO2), were measured. NDI was defined as death or a cognitive score &lt;85 on the Bayley Scales of Infant and Toddler Development. The predictive ability of individual biomarkers (TSS, DP, and NVC) and their combination for NDI was evaluated using receiver operating characteristic (ROC) curves, with the area under the ROC curve (AUC) indicating prediction accuracy. Additionally, a Net Reclassification Index (NRI) analysis was conducted to assess the predictive performance of the three baseline models (TSS, DP, and NVC).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Forty-six newborns with mild to severe HIE were enrolled and neuromonitoring was initiated at 12 ± 6 h of life. Death or NDI was diagnosed in 18 (6 mild, 10 moderate, 2 severe) infants. Eight out of 46 infants did not complete the 18-24 months follow-up but had a normal examination prior. The combination of all three biomarkers (TSS, DP, and NVC) yielded the highest AUC of 0.755 (95% CI: 0.569-0.941), with sensitivity of 0.750, specificity of 0.769, positive predictive value of 0.800, and negative predictive value of 0.714, outperforming individual biomarkers or two-marker combinations. Furthermore, the NRI analysis demonstrated that the combined model achieved the highest NRI value (0.5577), indicating the strongest improvement in risk classification.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This study emphasizes the importance of implementing multimodal neuromonitoring and integrating quantitative biomarkers at the bedside during the first day of life to provide objective metrics on brain health in addition to neurological exam. These approaches demonstrate potential for enhancing the prediction of encephalopathy severity, brain injury, and NDI in th","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-12"},"PeriodicalIF":2.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774819","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":"New-onset OCD and juvenile enthesitis related arthritis after COVID-19 (Three Cases).","authors":"Tanya Saini, Meiqian Ma, Jesse Sandberg, Bahare Farhadian, Cindy Manko, Yuhuan Xie, Juliette Madan, Karen Bauer, Paula Tran, Jennifer Frankovich","doi":"10.1159/000545137","DOIUrl":"https://doi.org/10.1159/000545137","url":null,"abstract":"<p><p>Introduction Obsessive-compulsive disorder (OCD) is a mental health disorder characterized by obsessions and compulsions. There is a mounting body of evidence suggesting a link between OCD and inflammation. Neuropsychiatric deteriorations have been reported to follow COVID-19 infections, including OCD. Additionally, symptomatic arthritis has also been reported following COVID-19 infection. We aim to describe post-COVID-19 clinical deteriorations presenting to our multi-discplinary immune behavioral health clinic. Methods 151 pre-screened patients were evaluated in our clinic between March 1, 2020 and August 1, 2024. We systematically searched charts for infection with SARS-CoV-2 and found three cases of confirmed COVID-19 infection that preceded an abrupt neuropsychiatric deterioration (in the absence of other detected infections). Per our clinic's latest protocol, all patients underwent a full rheumatology and arthritis evaluation (regardless of joint complaints) including ultrasound imaging which were used to objectively assess for effusions, synovitis, and capsulitis. Results Two of the three patients met criteria for a PANS diagnosis. All three patients had new-onset OCD or re-escalation of OCD with new obsessions/compulsions/rituals post-COVID-19 and all three had imaging findings of effusions +/- synovitis +/- capsulitis despite not having significant complaints of joint pain. Joint pain complaints evolved after psychiatric symptoms improved (because the capacity of the patient to articulate joint pain improved when they were less overwhelmed by intrusive thoughts). Immunomodulatory treatment began with nonsteroidal anti-inflammatory drugs (NSAIDs) and was escalated to disease-modifying antirheumatic drugs (DMARDs) in the two patients with synovitis +/- capsulitis. All three patients eventually returned to baseline neuropsychiatric health (minimal-to-no OCD and resolution of intense anxiety and mood instability) and also had improvement in arthritic findings after introduction of NSAID +/- DMARDs. Conclusion Infections may result in systemic immune activation leading to inflammation. Thus, when patients have an acute neuropsychiatric deterioration (hypothesized to have been triggered by an infection), the situation may warrant evaluation for inflammation in other more accessible sites (e.g. joints). Use of this evidence of inflammation (as a sign of immune activation) is helpful since it is difficult to assess for brain inflammation, as clinical brain imaging has poor sensitivity for inflammation and biopsy of the striatum (and other areas involved in OCD) is difficult and limited by risk. In our cases, early joint imaging not only helped confirm signs of systemic inflammation in the setting of neuropsychiatric symptoms, it also allowed for earlier initiation of immunomodulatory treatment.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-29"},"PeriodicalIF":2.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774820","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":"Hypothermia treatment in Hypoxia-Inducible Factor-1α Knockout Mice with Hypoxia-Ischemia.","authors":"R Ann Sheldon, Xiangning Jiang, Fuxin Lu, Nicholas R Stewart, Donna M Ferriero","doi":"10.1159/000544949","DOIUrl":"10.1159/000544949","url":null,"abstract":"<p><strong>Introduction: </strong>Hypoxia-inducible factor-1α (HIF-1α) has a wide-ranging role in the cellular responses to hypoxia. We previously found that neuron-specific HIF-1α-deficient mice (HIF-KO) that underwent neonatal hypoxia-ischemia (HI) had increased brain injury suggesting its neuroprotective function. To investigate whether HIF-1α is also involved in the mechanisms of protection by hypothermia (HT), the standard of care for hypoxic-ischemic encephalopathy, we tested the effect of HT on HIF-KO and wild-type (WT) littermates after HI in postnatal day 9 mice.</p><p><strong>Methods: </strong>Cooling at 32°C began 1 h following HI and lasted for 3.5 h. Mice were perfused 5-7 days later for histological determination of injury severity. For Western blots, mice were killed 4 h or 24 h after HI with HT or HI with normothermia (NT) and ipsilateral cortices and hippocampi were evaluated for expression of HIF-1α, spectrin, ERK1/2, phosphorylated-ERK1/2 (p-ERK), and RNA-binding motif protein 3 (RBM3), one of the main cold-inducible mRNA-binding proteins.</p><p><strong>Results: </strong>Histological evaluation showed WT mice with HT had less injury than WT with NT, but HIF-KO mice showed no reduction of injury with HT. Regionally, the reduction of injury in WT with HT is greater in the hippocampus than in the cortex. Protein expression of HIF-1α was lower in HIF-KO cortex at 4 h with NT or HT and at 24 h with NT, but HIF-1α was higher in WT with NT at 24 h. Expression of spectrin 145/150 in WT cortex with HT was not different than sham at 4 h, indicating limitation of necrosis with HT. In the HIF-KO cortex at 4 h spectrin 145/150 was higher in both NT and HT, indicating no protection with HT. In the hippocampus at 4 h and 24 h, spectrin 145/150 was elevated in all groups compared to sham. ERK activity, as represented by the ratio of p-ERK/ERK, was upregulated at 24 h in the cortex in WT with NT or HT compared to sham and in HIF-KO mice with NT or HT treatment compared to sham. RBM3 was elevated at 4 h in both WT and HIF-KO cortex with HT, but there was no change in the hippocampus.</p><p><strong>Conclusion: </strong>These results support a critical role for HIF-1α in the mechanisms of protection with HT.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-10"},"PeriodicalIF":2.3,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755738","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":"Aquaporins: Bridging Normal Brain Development and Neurodevelopmental Disorder Mechanisms.","authors":"Fateme Azizi, Wing Ki Chan, Maryam Ardalan","doi":"10.1159/000545512","DOIUrl":"10.1159/000545512","url":null,"abstract":"<p><strong>Background: </strong>Homeostasis of water content in the brain during fetal development is of crucial physiological importance. Aquaporins (AQPs) play a critical role in maintaining brain water balance, supporting normal brain development, and are increasingly recognized for their relevance in understanding neurodevelopmental disorders.</p><p><strong>Summary: </strong>This review provides a comprehensive overview of AQPs and their essential roles in the central nervous system (CNS), specifically AQP4, AQP11, and AQP9, which play a crucial role in water transport in the brain, maintaining water homeostasis and facilitating water movement across cell membranes. The review also highlights how disruptions in AQP expression and function may contribute to the pathology of neurodevelopmental disorders such as autism and Fragile X syndrome.</p><p><strong>Key messages: </strong>AQPs are vital for brain water regulation and normal neural development. Altered expression or function of AQPs can impact blood-brain barrier integrity, neuroinflammation, and synaptic activity. AQP dysfunctions are linked to neurodevelopmental disorders and may represent promising therapeutic targets.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-15"},"PeriodicalIF":2.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732834","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":"Selective Injury of Thalamocortical Tract in Neonatal Rats Impairs Forelimb Use: Model Validation and Behavioral Effects.","authors":"Tong Chun Wen, Michelle Corkrum, Jason B Carmel","doi":"10.1159/000544990","DOIUrl":"10.1159/000544990","url":null,"abstract":"<p><strong>Introduction: </strong>Unilateral brain injury in neonates results in largely contralateral hand function impairment in children. Most research investigating neurorehabilitation targets for movement recovery has focused on the effects of brain injury on descending motor systems, especially the corticospinal tract. However, a recent human study demonstrated that sensory tract injury may have larger effects on dexterity than motor tract injury. To test this, we first developed a model of sensory tract injury in neonatal rats by targeting the thalamocortical tract (TCT), and then we used this model to assess the effects of sensory lesions on paw use.</p><p><strong>Methods: </strong>In the postnatal day 7 rats, we used three types of lesions to the TCT: periventricular blood injection, photothrombotic lesion, and electrolytic lesion. To test the sensitivity and specificity of these techniques, viral tracers were injected into the primary sensory or motor cortex immediately after injury. To test the forelimb use, the cylinder exploration and pasta handling tests were used.</p><p><strong>Results: </strong>Electrolytic lesions were the most specific and reproducible for inducing a lesion compared to the other two methods. Electrolytic lesions disrupted 63% of the TCT while sparing the adjacent corticospinal tract in the internal capsule. Given that electrolytic lesions were the most specific and sensitive for targeting the TCT, this model was used for behavioral experiments to measure the impact of sensory tract lesion on dexterity. Lesions to the TCT were associated with a significant decrease in the use of the contralateral forelimb in the cylinder task, and the degree of impairment positively correlated with the degree of injury.</p><p><strong>Conclusion: </strong>Overall, specific sensory system lesions of the TCT impair forelimb use, suggesting a key role for skilled movement.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-12"},"PeriodicalIF":2.3,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711968","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}