記述言語：英語   出版者・発行元：Journal of Perinatology  

Objective: To evaluate the relationship between postnatal growth by term and high-performing neurodevelopment in infants born at less than 28 weeks of gestational age. Methods: This retrospective study examined associations between anthropometric Z-scores (length, weight, head circumference) at 32, 36, and 40 weeks postmenstrual age (PMA) and neurodevelopment at age 3 categorized into four groups (delay, subnormal, normal, high-performing). Results: A total of 287 infants were evaluated. Body length at 40 weeks PMA was significantly associated with high-performing neurodevelopment (adjusted OR = 1.86, 95% CI = 1.49–2.32), followed by head circumference (adjusted OR = 1.32, 95% CI = 1.04-67). Changes in body length Z-scores from 36 to 40 weeks PMA were significantly associated with high-performing neurodevelopment, whereas body weight and earlier changes in Z-scores were not. Conclusions: In extremely preterm infants, body length growth by 40 weeks PMA was an independent predictor for high-performing neurodevelopment at age 3, whereas body weight and earlier growth changes did not.

DOI： 10.1038/s41372-026-02692-z

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記述言語：英語   出版者・発行元：Pediatric Radiology  

Background: In congenital diaphragmatic hernia, postoperative right-left asymmetry of pulmonary perfusion affects outcome. Although pulmonary perfusion scintigraphy (PPS) is widely used to assess pulmonary perfusion, it requires the use of radionuclides and peripheral venous access. In contrast, dynamic digital radiography (DDR) visualizes and analyzes pulmonary perfusion by extracting subtle changes in X-ray attenuation from sequential images acquired using a pulsed X-ray generator and a flat-panel detector. Objective: This study aimed to evaluate the accuracy of DDR for assessing pulmonary perfusion in children and verify the associated radiation dose. Materials and methods: Consecutive congenital diaphragmatic hernia survivors aged 5–7 years scheduled for routine PPS between January 2024 and June 2025 underwent DDR on the same day. The images were analyzed using a dedicated workstation. For each modality, we calculated the blood-flow ratio in the affected lung and assessed the agreement using Pearson correlation and Bland–Altman analysis. Effective doses were also compared. Results: Thirteen children (median age, 6.07 years; 10 left-sided diaphragmatic hernia) were included in the study. DDR-derived blood-flow ratio strongly correlated with PPS (r=0.977, P<0.01), with absolute inter-method blood-flow ratio differences <5%. Neither fixed nor proportional bias was observed. The median effective dose for DDR was 0.16 mSv—significantly lower than that for PPS (2.09 mSv). The blood-flow ratio calculated using DDR correlated well with the scintigraphy results. Conclusion: DDR could serve as a minimally invasive, low-dose alternative to PPS for the evaluation of pulmonary perfusion. Future validation in a broader pediatric population is warranted.

DOI： 10.1007/s00247-026-06589-z

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記述言語：英語   出版者・発行元：Pediatric Research  

Background: An association between total hydrocortisone (HC) dosage in infants with extremely low birth weight (ELBW) and subsequent neurodevelopmental outcomes up to school age remains unclear. Method: We conducted a retrospective longitudinal cohort study across eight centers in Japan, including ELBW infants born between 2015 and 2017. We investigated the association between total HC dosage administered up to 36 weeks postmenstrual age and neurodevelopmental outcomes to school age. Results: Linear mixed model analysis showed a significant association between higher HC dosage and lower developmental and intelligence quotient (DQ/IQ) scores. This trend persisted at 6 years of age, suggesting a sustained effect of HC on cognitive outcomes. For every 10 mg increase in HC dosage, IQ scores decreased by 2.82 points (95% CI: −3.89 to −1.06, p = 0.001). The interaction term between HC dosage and time was not statistically significant (0.10, 95% CI: −0.18 to 0.37, p = 0.481), suggesting the association of HC dosage on DQ/IQ did not vary substantially throughout the study period. Conclusions: We found a relationship between total neonatal HC dosage in ELBW infants and DQ/IQ scores over time that persisted at school age. Clinicians should be aware of this potential dose-dependent effect on neurodevelopmental outcomes. Impact: As neonatal dexamethasone administration is known to affect neurodevelopment outcomes, hydrocortisone (HC) is considered an alternative to dexamethasone as a glucocorticoid treatment. In infants with extremely low birth weight (ELBW), a relationship has been noted between total HC dosage and neurodevelopment in early childhood. We confirmed the association between total HC dosage in infants with ELBW and poor developmental and intelligence quotients to school age. Although HC is commonly used in the management of ELBW infants, clinicians should be aware of its potential dose-dependent effects on neurodevelopmental outcomes.

DOI： 10.1038/s41390-025-04426-x

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記述言語：英語   出版者・発行元：Stem Cell Research and Therapy  

Background: Effective treatments for cerebral palsy caused by Hypoxic-ischemic encephalopathy are urgently needed. Current therapies primarily include prevention or acute intervention, leaving a major gap in the options for reversing established neurologic damage. Because of their ease of collection and unique trophic factor profile, stem cells from human exfoliated deciduous teeth (SHED) are promising candidates for cell-based therapy targeting neurological disorders. In this study, we examined the therapeutic potential of SHED in a rat model of cerebral palsy, focusing on neurogenic and functional recovery. Methods: Hypoxic–ischemic encephalopathy was induced in neonatal rats using the Rice–Vannucci method. Rats with motor impairments received intravenous SHED injections, whereas the control group received a vehicle solution. Behavioral tests assessed motor coordination and cognitive performance. Proteomic analyses and immunohistochemistry were performed to examine the underlying mechanisms. The migration and biodistribution of SHED were tracked using quantum dot-labeled SHED with in vivo imaging. Neural stem cells were cocultured with SHED to evaluate neurogenesis, followed by RNA sequencing and the analysis of trophic factors in the conditioned media. Results: SHED treatment significantly ameliorated motor coordination, memory, and learning. Proteomic analysis revealed increased expression of proteins associated with neurogenesis in the SHED group. Histopathologic evaluations revealed enhanced neurogenesis in the hippocampal dentate gyrus and subventricular zone 2 weeks posttreatment, with increased NeuN-positive cells in the hippocampus and cortex at ten weeks. In vivo imaging revealed the migration of quantum dot-labeled SHED to the brain. Neural stem cells co-cultured with SHED in vitro exhibited higher proliferation rates. The SHED-conditioned medium contained increased levels of hepatocyte growth factor (HGF), and HGF-neutralizing antibodies suppressed the enhanced cell proliferation. RNA sequencing revealed significant alterations in genes associated with the PI3K–Akt signaling pathway. Conclusions: SHED treatment ameliorated motor, memory, and learning impairment in a rat model of cerebral palsy. These improvements were accompanied by enhanced neurogenesis, likely mediated by HGF secretion and activation of the PI3K–Akt signaling pathway. SHED is a promising candidate for postsymptom-onset treatment of cerebral palsy. Further studies to confirm these findings and examine the clinical utility of SHED are warranted.

DOI： 10.1186/s13287-025-04828-y

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記述言語：英語   出版者・発行元：Scientific Reports  

In humans, fetal cerebellar development peaks during the final stages of pregnancy. Preterm infants experience hyperoxia (excessive oxygen) outside the uterus. Hyperoxia exposure causes neurological deficits in preterm infants. However, detailed mechanisms underlying hyperoxia-induced neurological deficits remain unclear. Previous studies on neurological deficits have focused on cerebral lesions. However, recently, cerebellar lesions have been observed on brain magnetic resonance imaging in preterm infants. We herein aimed to investigate behavioral and cerebellar tissue–level changes in Sprague–Dawley rat neonates exposed to 83% hyperoxia from within 24 h of birth to 14 days of age. In rats, cerebellar development peaks in the first postnatal week. We elucidated the mechanism by which hyperoxia exposure causes neurological deficits in these rats. We found that prolonged hyperoxia exposure, starting within 24 h of birth, induces behavioral impairments (such as motor, cognitive and memory, and social interaction deficits) in rats. At the tissue level, delayed granule cell migration and abnormal Purkinje cell dendritic development combined with impaired myelination were observed in the acute and chronic hyperoxia exposure phases, respectively. Thus, hyperoxia exposure may cause abnormalities in cerebellar morphology and function, resulting in neurological deficits in preterm infants.

DOI： 10.1038/s41598-025-34530-1

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記述言語：英語   出版者・発行元：Pediatrics International  

DOI： 10.1111/ped.70439

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記述言語：英語   出版者・発行元：Pediatrics International  

DOI： 10.1111/ped.70122

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記述言語：英語   出版者・発行元：Stem Cells Translational Medicine  

Hypoxic–ischemic encephalopathy (HIE), associated with high mortality and neurological sequelae, lacks established treatment except therapeutic hypothermia. Clinical-grade multilineage-differentiating stress-enduring (Muse) cells (CL2020) demonstrated safety and efficacy in nonclinical HIE rat models, thereby leading to an investigator-initiated clinical trial to evaluate CL2020 safety and tolerability in neonatal HIE as a single-center open-label dose-escalation study with 9 neonates with moderate-to-severe HIE who received therapeutic hypothermia. Each patient received a single intravenous injection of CL2020 cells between 5 and 14 days of age. The low-dose (3 patients) and high-dose (6 patients) groups received 1.5 × 10⁶ and 1.5 × 10⁷ cells/dose, respectively. The occurrence of any adverse event within 12 weeks following CL2020 administration was the primary endpoint of this trial. No significant changes in physiological signs including heart rate, blood pressure, and oxygen saturation were observed during or after administration. The only adverse event that may be related to cell administration was a mild γ-glutamyltransferase level elevation in one neonate, which spontaneously resolved without any treatment. All patients enrolled in the trial survived, and normal developmental quotients (≥ 85) in all 3 domains of the Kyoto Scale of Psychological Development 2001 were observed in 67% of the patients in this trial. CL2020 administration was demonstrated to be safe and tolerable for neonates with HIE. Considering the small number of patients, a randomized controlled confirmatory study is warranted to verify these preliminary findings and evaluate the efficacy of this therapy.

DOI： 10.1093/stcltm/szae071

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Neonatology  

Introduction: The effects of hydrocortisone (HDC) administration to extremely low birth weight (ELBW) infants on later development remain unclear. This study examined the association between HDC dosage during neonatal period and neurodevelopmental outcomes in ELBW infants. Methods: This study was a retrospective cohort study conducted in eight centers in Japan. The subjects of this study were ELBW infants born between April 2015 and March 2017. The association between postnatal total HDC dosage up to 36 weeks postmenstrual age and the developmental quotient (DQ) at 3 years of age was examined. Multiple linear regression evaluated the association, adjusting for weeks of gestation, birth weight, and the presence of bronchopulmonary dysplasia, late-onset circulatory collapse, intracranial hemorrhage, necrotizing enterocolitis, and sepsis. Results: This study included 218 ELBW infants, of whom 144 underwent a developmental test at 3 years of age. Simple linear regression analysis revealed a significant association between total HDC dosage and DQ at 3 years of age (coefficients: −2.65, 95% CI: −3.73, −1.57). Multiple linear regression analysis adjusted for the presence of bronchopulmonary dysplasia and late-onset circulatory collapse also revealed a significant association between total HDC dosage and DQ at 3 years of age (coefficients: −2.66, 95% CI: −3.89, −1.42). Conclusion: Higher total HDC dosage up to 36 weeks postmenstrual age in ELBW infants was associated with impaired neurodevelopmental outcomes. Although HDC is often needed in the treatment of ELBW infants, clinicians should be aware that an increased dose of HDC may be associated with impaired neurodevelopmental outcomes.

DOI： 10.1159/000534934

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記述言語：英語   出版者・発行元：Scientific Reports  

Multilineage-differentiating stress-enduring (Muse) cells are endogenous reparative pluripotent stem cells present in the bone marrow, peripheral blood, and organ connective tissues. We assessed the homing and therapeutic effects of systemically administered nafimestrocel, a clinical-grade human Muse cell-based product, without immunosuppressants in a neonatal hypoxic–ischemic (HI) rat model. HI injury was induced on postnatal day 7 (P7) and was confirmed by T2-weighted magnetic resonance imaging on P10. HI rats received a single dose nafimestrocel (1 × 10⁶ cells/body) or Hank’s balanced salt solution (vehicle group) intravenously at either three days (on P10; M3 group) or seven days (on P14; M7 group) after HI insult. Radioisotope experiment demonstrated the homing of chromium-51-labeled nafimestrocel to the both cerebral hemispheres. The cylinder test (M3 and M7 groups) and open-field test (M7 group) showed significant amelioration of paralysis and hyperactivity at five weeks of age compared with those in the vehicle group. Nafimestrocel did not cause adverse events such as death or pathological changes in the lung at ten weeks in the both groups. Nafimestrocel attenuated the production of tumor necrosis factor-α and inducible nitric oxide synthase from activated cultured microglia in vitro. These results demonstrate the potential therapeutic benefits and safety of nafimestrocel.

DOI： 10.1038/s41598-023-41026-3

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記述言語：英語   出版者・発行元：Pediatrics International  

DOI： 10.1111/ped.15698

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記述言語：英語   出版者・発行元：Frontiers in Pediatrics  

Introduction: To investigate the mechanism underlying the increased risk of subsequent neurodevelopmental disorders in children born to mothers with preeclampsia, we evaluated the neurodevelopment of offspring of a preeclampsia rat model induced by the administration of N-nitro-L-arginine methyl ester (L-NAME) and identified unique protein signatures in the offspring cerebrospinal fluid. Methods: Pregnant rats received an intraperitoneal injection of L-NAME (250 mg/kg/day) during gestational days 15–20 to establish a preeclampsia model. Behavioral experiments (negative geotaxis, open-field, rotarod treadmill, and active avoidance tests), immunohistochemistry [anti-neuronal nuclei (NeuN) staining in the hippocampal dentate gyrus and cerebral cortex on postnatal day 70], and proteome analysis of the cerebrospinal fluid on postnatal day 5 were performed on male offspring. Results: Offspring of the preeclampsia dam exhibited increased growth restriction at birth (52.5%), but showed postnatal catch-up growth on postnatal day 14. Several behavioral abnormalities including motor development and vestibular function (negative geotaxis test: p < 0.01) in the neonatal period; motor coordination and learning skills (rotarod treadmill test: p = 0.01); and memory skills (active avoidance test: p < 0.01) in the juvenile period were observed. NeuN-positive cells in preeclampsia rats were significantly reduced in both the hippocampal dentate gyrus and cerebral cortex (p < 0.01, p < 0.01, respectively). Among the 1270 proteins in the cerebrospinal fluid identified using liquid chromatography-tandem mass spectrometry, 32 were differentially expressed. Principal component analysis showed that most cerebrospinal fluid samples achieved clear separation between preeclampsia and control rats. Pathway analysis revealed that differentially expressed proteins were associated with endoplasmic reticulum translocation, Rab proteins, and ribosomal proteins, which are involved in various nervous system disorders including autism spectrum disorders, schizophrenia, and Alzheimer's disease. Conclusion: The offspring of the L-NAME-induced preeclampsia model rats exhibited key features of neurodevelopmental abnormalities on behavioral and pathological examinations similar to humans. We found altered cerebrospinal fluid protein profiling in this preeclampsia rat, and the unique protein signatures related to endoplasmic reticulum translocation, Rab proteins, and ribosomal proteins may be associated with subsequent adverse neurodevelopment in the offspring.

DOI： 10.3389/fped.2023.1168173

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記述言語：英語  

DOI： 10.3389/fncel.2020.00212

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記述言語：英語  

DOI： 10.1136/bmjopen-2021-057073

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DOI： 10.1089/scd.2019.0221

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DOI： 10.3389/fneur.2018.00987

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DOI： 10.3389/fneur.2018.00757

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担当区分：筆頭著者   記述言語：日本語   掲載種別：研究論文（学術雑誌）  

DOI： 10.11251/ojjscn.45.21

Open Access

担当区分：筆頭著者   記述言語：日本語   掲載種別：記事・総説・解説・論説等（商業誌、新聞、ウェブメディア）  

担当区分：筆頭著者   記述言語：日本語   掲載種別：記事・総説・解説・論説等（商業誌、新聞、ウェブメディア）  

担当区分：筆頭著者   記述言語：日本語   掲載種別：記事・総説・解説・論説等（商業誌、新聞、ウェブメディア）  

開催年月日： 2022年11月

記述言語：日本語   会議種別：公開講演，セミナー，チュートリアル，講習，講義等  

開催地：パシフィコ横浜  

開催年月日： 2017年10月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：埼玉   国名：日本国  

開催年月日： 2017年10月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：埼玉   国名：日本国  

開催年月日： 2017年6月

記述言語：英語   会議種別：口頭発表（一般）  

開催地：Boston, USA   国名：アメリカ合衆国