Hydrogen gas can ameliorate seizure burden during therapeutic hypothermia in asphyxiated newborn piglets.

BACKGROUND: We previously reported that hydrogen (H2) gas combined with therapeutic hypothermia (TH) improved short-term neurological outcomes in asphyxiated piglets. However, the effect on seizure burden was unclear. Using amplitude-integrated electroencephalography (aEEG), we compared TH + H2 with TH alone in piglets 24 h after hypoxic-ischemic (HI) insult. METHODS: After a 40-min insult and resuscitation, 36 piglets ≤24 h old were divided into three groups: normothermia (NT, n = 14), TH alone (33.5 ± 0.5 °C, 24 h, n = 13), and TH + H2 (2.1-2.7% H2 gas, 24 h, n = 9). aEEG was recorded for 24 h post-insult and its background pattern, status epilepticus (SE; recurrent seizures lasting >5 min), and seizure occurrence (Sz; occurring at least once but not fitting the definition of SE) were evaluated. Background findings with a continuous low voltage and burst suppression were considered abnormal. RESULTS: The percentage of piglets with an abnormal aEEG background (aEEG-BG), abnormal aEEG-BG+Sz and SE was lower with TH + H2 than with TH at 24 h after HI insult. The duration of SE was shorter with TH + H2 and significantly shorter than with NT. CONCLUSIONS: H2 gas combined with TH ameliorated seizure burden 24 h after HI insult. IMPACT: In this asphyxiated piglet model, there was a high percentage of animals with an abnormal amplitude-integrated electroencephalography background (aEEG-BG) after hypoxic-ischemic (HI) insult, which may correspond to moderate and severe hypoxic-ischemic encephalopathy (HIE). Therapeutic hypothermia (TH) was associated with a low percentage of piglets with EEG abnormalities up to 6 h after HI insult but this percentage increased greatly after 12 h, and TH was not effective in attenuating seizure development. H2 gas combined with TH was associated with a low percentage of piglets with an abnormal aEEG-BG and with a shorter duration of status epilepticus at 24 h after HI insult.

Developmental changes in neonatal hemodynamics during tactile stimulation using whole-head functional near-infrared spectroscopy.

Neural-activity-associated hemodynamic changes have been used to noninvasively measure brain function in the early developmental stages. However, the temporal changes in their hemodynamics are not always consistent with adults. Studies have not evaluated developmental changes for a long period using the same stimuli; therefore, this study examined the normalized relative changes in oxygenated hemoglobin (Δ[oxy-Hb]) in full-term infants and compared them with neonates up to 10 months of age during the administration of tactile vibration stimuli to their limbs using whole-head functional near-infrared spectroscopy. The time to peak of normalized Δ[oxy-Hb] was not affected by age. The amplitude of normalized Δ[oxy-Hb] showed an effect of age in broader areas, including sensorimotor-related but excluding supplementary motor area; the amplitude of normalized Δ[oxy-Hb] decreased the most in the 1-2-month-old group and later increased with development. We hypothesized that these results may reflect developmental changes in neural activity, vasculature, and blood oxygenation.

Maternal separation early in life induces excessive activity of the central amygdala related to abnormal aggression.

Epidemiological studies have indicated that child maltreatment, such as neglect, is a risk factor of escalated aggression, potentially leading to delinquency and violent crime in the future. However, little is known about the mechanisms by which an early adverse environment may later cause violent behavior. In this study, we aimed to thoroughly examine the association between aggression against conspecific animals and the activity of amygdala subnuclei using the maternal separation (MS) model, which is a common model of early life stress. In the MS group, pups of Sprague-Dawley rats were separated from their dam during postnatal days 2-20 (twice a day, 3 h each). We only included 9-week-old male offspring for each analysis and compared the MS group with the mother-reared control group; both groups were raised by the same dam during postnatal days 2-20. The results revealed that the MS group exhibited higher aggression and excessive activity of only the central amygdala (CeA) among the amygdala subnuclei during the aggressive behavior test. Moreover, a significant positive correlation was observed between higher aggression and CeA activation. While CeA activity is known to be involved in hunting behavior for prey, some previous studies have also indicated a relationship between CeA and intraspecific aggression. It remains unclear, however, whether excessive CeA activity directly induces intraspecific aggression. Therefore, we stimulated the CeA using optogenetics with 8-week-old rats to clarify the relationship between intraspecific aggression and CeA activity. Notably, CeA activation resulted in higher aggression, even when the opponent was a conspecific animal. In particular, bilateral CeA activation resulted in more severe displays of aggressive behavior than necessary, such as biting a surrendered opponent. These findings suggest that an adverse environment during early development intensifies aggression through excessive CeA activation, which can increase the risk of escalating to violent behavior in the future.

Problematic internet use and attachment styles among adolescents in Japan.

BACKGROUND: Problematic Internet use (PIU) remains a significant social concern in Japan and across the globe. Numerous studies have been conducted to examine the prevalence of PIU, and its association with lifestyle habits and mental health status. To the best of our knowledge, few studies have examined the association between parental attachment and PIU in Japan. Furthermore, preventive measures in Japan have primarily targeted adolescents via education. Therefore, in this study we explored the association between PIU and attachment styles among adolescents to seek a new approach for the development of appropriate, effective measures. METHODS: A self-administered survey was conducted at one private (in 2018) and two public junior high schools (in 2020) in Kagawa Prefecture, western Japan. We used the Internet Addiction Test (IAT), the Experiences in Close Relationships-Relationship Structures (ECR-RS) questionnaire, and the Birleson Depression Self-Rating Scale for Children (DSRS-C). Multiple regression analysis was performed to examine the association between IAT scores and attachment styles. RESULTS: Of 1,413 participants (grades 7-9; 700 boys and 713 girls), 39% of the students showed possible PIU and 3% showed PIU. Students with PIU tended to sleep for shorter durations, access the Internet for long hours, and have a poor mental health status (p < 0.01). PIU was significantly associated with insecure attachment (p < 0.0001). CONCLUSIONS: The findings of our study imply that improving attachment styles and developing secure attachment between the child and parent might help mitigate and/or prevent PIU.

Current status of neonatal jaundice management in Japan.

BACKGROUND: This nationwide survey aimed to determine the status of jaundice management in Japan. METHODS: A questionnaire about bilirubin level measurements and neonatal jaundice treatment was sent to 330 institutions providing neonatal care. The responses were analyzed according to institution level. RESULTS: Of 330 institutions, 172 responded (52.1% response rate). Total bilirubin levels were measured in the central laboratory using spectrophotometry at 134 institutions and a blood gas analyzer at 81 institutions. Unbound bilirubin (UB) levels were measured by 79 institutions, while transcutaneous bilirubin measurements were taken at 63 institutions. There was no association between institution level and UB or transcutaneous bilirubin measurement. For phototherapy criteria, the Murata-Imura criteria were adopted by 67 institutions, Nakamura criteria by 36, and Morioka criteria by 39. Light-emitting diodes (LED) were used by 160 institutions versus fluorescent lights by 31. When a blue LED was used, 119 institutions used the high mode. There is no standard for increasing light intensity. No association was found between institution level and phototherapy criteria. UB was measured in 14 of 63 institutions using the Murata-Imura criteria. CONCLUSIONS: There is a large variation in the management and treatment of neonatal jaundice among institutes in Japan.

Medical care of newborns born to mothers with confirmed or suspected severe acute respiratory syndrome coronavirus 2 infections in Japan.

BACKGROUND: There are currently no definitive guidelines regarding newborns born to mothers with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aimed to investigate the medical care and management that provided or would provide for such newborns. METHODS: A web survey was conducted between September and October 2020. A total of 624 hospitals, which generally accept pregnant women for delivery, were involved in this study. The survey included the number of newborns born to mothers with confirmed SARS-CoV-2 infection and evaluated policies regarding the medical care and management of newborns born to mothers with confirmed or suspected SARS-CoV-2 infection. RESULTS: Pregnant women with confirmed or suspected SARS-CoV-2 infection were accepted or planned to be accepted in 54% (334) of the hospitals. Out of 52 newborns born to mothers with confirmed SARS-CoV-2 infection, SARS-CoV-2 RNA was detected from the nasopharyngeal swab of one newborn shortly after birth. The types of personal protective equipment during the delivery, the separation of the newborns from the mothers, the SARS-CoV-2 testing methods, and the use of incubators during the quarantine period were uniformly provided. However, the methods of ventilator treatment in the event of respiratory disorders, feeding during maternal isolation, and de-quarantine and discharge criteria varied. CONCLUSIONS: This survey demonstrated that one newborn detected a SARS-CoV-2 RNA shortly after birth out of 52 newborns who were born to mothers with confirmed SARS-CoV-2 infection. The policies regarding medical care and management for these newborns in Japan were provided.

Cerebral hemoglobin oxygenation in children with congenital heart disease.

BACKGROUND: It is important to identify the pathological characteristics of cerebral circulation and oxygen metabolism at the bedside in children with congenital heart disease (CHD) to prevent neurodevelopmental impairments. The brain regional oxygen saturation index (rSO2 ) can be easily obtained at the bedside with near-infrared spectroscopy and has been widely used in the management of children with CHD in recent years. METHODS: To determine if the rSO2 before or after CHD surgery is a good predictor of cerebral oxygen metabolism, we investigated the impact of different clinical variables on the correlation between rSO2 and reference values under steady ratios of hemoglobin oxygen saturation in the internal jugular vein (SjvO2 ) or femoral artery (SaO2 ) (0.75:0.25, 0.66:0.34, and 0.50:0.50) in 186 children with CHD undergoing cardiac catheterization. RESULTS: In three patient groups-double ventricles before surgery, double ventricles after surgery, and single ventricle before surgery-there were significant relationships between rSO2 and the reference values of SO2 under all three steady ratios of SjvO2 and SaO2 . No relationship with the reference values was found for the single ventricle after surgery group. CONCLUSIONS: Regional oxygen saturation index is useful for assessing cerebral oxygenation in children with CHD, but knowledge of the underlying cardiac pathology in CHD, especially in the case of a single ventricle after surgery, is important for the correct interpretation of rSO2 measurements obtained using near-infrared spectroscopy.

Furosemide clearance in very preterm neonates early in life: A pilot study using scavenged samples.

BACKGROUND: Furosemide is an off-label drug, frequently used as a diuretic in neonates with oliguria and/or edema. Its clearance in preterm neonates is lower than in term neonates or children. We aimed, herein, to clarify furosemide clearance (CL) in very preterm (VP) neonates (<28 weeks' gestation) within the first 2 weeks of life and identify the factors predictive of the pharmacokinetics (PK) parameters, such as CL. METHODS: Furosemide was administered at 0.5 or 1 mg/kg in a 0.5-h infusion via a syringe pump; blood samples were drawn from an artery or vein after the intravenous injection. The serum furosemide concentration was measured using high-performance liquid chromatography. The PK parameters were then analyzed using Bayesian estimation. RESULTS: Thirteen blood samples were obtained from 10 VP neonates after intravenous injection. The mean postconceptional age and mean postnatal days at exposure to furosemide were 26.9 weeks and 7.1 days, respectively. The estimated mean CL was 16.5 mL/kg/h. The mean distribution volume (Vd) and elimination half-life (t1/2) were 0.37 L/kg and 15.3 h, respectively. Furosemide CL was negatively associated with serum creatinine (SCr) [CL = 84.2 - 67.1 × SCr (mg/dL)]. CONCLUSIONS: Very preterm neonates within the first 2 weeks of life had a higher CL than subjects in other preterm neonatal studies. The SCr level was the sole parameter influencing furosemide CL and might serve as a good index for furosemide dosing in VP neonates.

Hypothermia cannot ameliorate renal fibrosis after asphyxia in the newborn piglet.

BACKGROUND: The effects of therapeutic hypothermia (TH) on renal function are not widely reported, especially in longer term animal models. The hypothesis of this study was that TH of the kidneys of hypoxic-ischemic newborn piglets would reduce pathological renal fibrosis. METHODS: Twenty-five newborn piglets obtained within 24 h of birth were classified into a control group (n = 5), an hypoxic insult with normothermia (HI-NT) group (n = 12), and an hypoxic insult with TH (HI-TH) group (33.5 °C ± 0.5 °C for 24 h; n = 8). Five days after the insult, all piglets were sacrificed under deep anesthesia by isoflurane inhalation. The kidneys were perfused with phosphate-buffered paraformaldehyde and immersed in formalin buffer. Territory fibrosis was studied and scored in the renal medulla using Azan staining. RESULTS: Fibrosis area scores (means ± standard deviations) based on Azan staining were 1.00 ± 0.46 in the control group, 2.85 ± 0.93 in the HI-NT group, and 3.58 ± 1.14 in the HI-TH group. The fibrosis area of the HI-NT and HI-TH groups was larger than that of the control. The HI-NT and HI-TH groups were not statistically different. CONCLUSIONS: Renal fibrosis is affected by perinatal asphyxia and cannot be prevented by TH, based on histopathological findings.

Stateful Rotor for Continuity of Quaternion and Fast Sensor Fusion Algorithm Using 9-Axis Sensors.

Advances in micro-electro-mechanical systems technology have led to the emergence of compact attitude measurement sensor products that integrate acceleration, magnetometer, and gyroscope sensors on a single chip, making them important devices in the field of three-dimensional (3D) attitude measurement for unmanned aerial vehicles, smartphones, and other devices. Sensor fusion algorithms for posture measurement have become an indispensable technology in cutting-edge research, such as human posture measurement using wearable sensors, and stabilization problems in robot position and posture measurement. We have also developed wearable sensors and powered suits in our previous research. We needed a technology for the real-time measurement of a 3D human body motion. It is known that quaternions can be used to algebraically handle 3D rotations; however, sensor fusion algorithms for three sensors are presently complex. This is because these algorithms deal with the post-rotation attitude (pure quaternions) rather than rotation information (the rotor) to avoid a double covering problem involving the rotor. If we are dealing with rotation, it may be possible to make the algorithm simpler and faster by dealing directly with the rotor. In this study, to solve the double covering problem involving the rotor, we propose a stateful rotor and develop a technique for uniquely determining the time-varying states of the rotor. The proposed stateful rotor guarantees the continuity of the rotor parameters with respect to angular changes, and this paper confirms its effectiveness by simulating two rotations around an arbitrary axis. In addition, we verify experimentally that a fast sensor fusion method using stateful rotor can be used for attitude calculation. Experiments also confirm that the calculated results converge to the desired rotation angle for two spatial rotations around an arbitrary axis. Since the proposed stateful rotor extends and stabilizes the definition of the rotor, it is applicable to any algorithm that deals with time-varying quaternionic rotors. In this research, an algorithm based on a multiply-add operation is designed to reduce computational complexity as a high-speed calculation for embedded systems. This method is theoretically equivalent to other methods, while contributing to power saving and the cost reduction of products.

Hydrogen and therapeutic gases for neonatal hypoxic-ischemic encephalopathy: potential neuroprotective adjuncts in translational research.

Numerous studies have examined the potential use of therapeutic gases for the treatment of various neurological disorders. Hydrogen gas, a promising neuroprotective agent, has been a focus of study due to its potent antioxidative properties. In translational research into adult diseases, hydrogen has been shown to be neuroprotective in disorders such as cerebral ischemia and traumatic brain injury, and in neurodegenerative diseases such as Alzheimer's disease. Animal and human studies have verified the safety and feasibility of molecular hydrogen. However, despite extensive research on its efficacy in adults, only a few studies have investigated its application in pediatric and neonatal medicine. Neonatal hypoxic-ischemic encephalopathy (HIE) is characterized by damage to neurons and other cells of the nervous system. One of the major contributing factors is excessive exposure to oxidative stress. Current research interest in HIE is shifting toward new neuroprotective agents, as single agents or as adjuncts to therapeutic hypothermia. Here, we review therapeutic gases, particularly hydrogen, and their potentials and limitations in the treatment of HIE in newborns. IMPACT: Translational animal models of neonatal HIE are a current focus of research into the therapeutic usefulness of various gases. Hydrogen ventilation as a single agent or in combination with therapeutic hypothermia shows short- and long-term neuroprotection in neonatal translational HIE models. The optimal target severity for therapeutic interventions should be well established to improve outcomes.

Developmental changes in urinary coproporphyrin ratio in premature infants.

BACKGROUND: Premature infants have a high concentration of conjugated bilirubin in their blood, although they have a poor glucuronide conjugation of bilirubin. This may be due to developmental changes in the function of adenosine triphosphate binding cassette subfamily C member 2, which is involved in the cellular export of conjugated bilirubin. In the present study, we examined the developmental changes in the urinary coproporphyrin I/(urinary coproporphyrin I+ urinary coproporphyrin III) ratio (UCP (I/ [I + III])), a known biomarker for adenosine triphosphate binding cassette subfamily C member 2 function, in premature infants. METHOD: Twenty-one premature infants born between 25 and 32 weeks of gestation were included in the study. Urine samples were collected within 24 h of birth, and at 1 week and 3-4 weeks after birth. The samples were analyzed by high-performance liquid chromatography to calculate UCP (I/ [I + III]) to examine its association with postnatal age and corrected gestational age. Subjects were excluded if they had liver dysfunction, cholestasis, urinary tract infection, or chromosomal abnormalities. RESULTS: The average UCP (I/ [I + III]) within 24 h of birth, at 1 week, and at 3-4 weeks after birth was 0.84, 0.61, and 0.65, respectively. The UCP (I/ [I + III]) within 24 h of birth was significantly higher than that measured at 1 week or 3-4 weeks after birth. There was no significant correlation between UCP (I/ [I + III]) and the corrected gestational age. CONCLUSION: The UCP (I/ [I + III]) was higher within 24 h of birth. It decreased 1 week after birth and remained low without any significant changes for up to 4 weeks after birth.

Hour-specific nomogram for transcutaneous Bilirubin in newborns in Myanmar.

BACKGROUND: Neonatal hyperbilirubinemia is a significant health problem in Myanmar, and the rate of kernicterus is also higher than in developed countries. Non-invasive methods for early detection and treatment of hyperbilirubinemia are urgently needed. In this study, we used transcutaneous bilirubin (TcB) measurements to develop an hour-specific TcB nomogram for the effective management of hyperbilirubinemia in Myanmar newborns. METHODS: The bilirubin levels of neonates born in Central Women Hospital in Yangon, Myanmar were measured three times a day within 72 h after birth using a transcutaneous bilirubinometer. An hour-specific TcB nomogram was created based on the data. RESULTS: Participants were 512 infants (287 boys, 225 girls) born in Central Women's Hospital in Yangon. The mean (±SD) gestational age was 38.4 ± 1.2 weeks; birthweight was 3078 ± 412 g. A total of 3,039 plots were obtained, and the TcB nomogram was created with smoothed percentile curves (97.5th, 50th, and 2.5th percentiles) for 0-72 h after birth. CONCLUSIONS: An hour-specific TcB nomogram was successfully created to manage hyperbilirubinemia in Myanmar newborns.

Behavior problems and dysfunctional parenting: Cross-sectional study in Japan.

BACKGROUND: The Japanese government has established a law encouraging early detection and treatment of developmental disorders in children. Child behavior problems (CBP) tend to be recognized at school as a result of developmental disorders. The aim of this study was to identify factors associated with CBP in Japan. We hypothesized that factors other than developmental disorders are important in explaining CBP. METHODS: The study was conducted between February and March 2015. Parents of 3,515 children aged 2-5 years attending one of 34 public nursery schools in Takamatsu, Kagawa, Japan received self-administered questionnaires addressing parental socioeconomic factors, mental health, parenting style (i.e. hostile, overreactive, or lax), developmental disorders in children, and CBP. A multiple regression analysis was applied to explore associations between CBP and possible factors. RESULTS: Overall, 1,410 mothers were eligible to participate in the study. Children diagnosed with developmental disorders accounted for 7.8% of the sample, while on the Eyberg Child Behavior Inventory 17% of children had behavior problems needing clinical intervention. After adjustment for confounding factors, as well as for the diagnosis of developmental disorders, poor mental status and all three dysfunctional parenting styles had strong associations with CBP, and hostile, overreactive, and lax parenting had standardized ß-values (ß) of 0.29, 0.28, and 0.15, respectively (P < 0.01). A problematic relationship between the parents was also significantly associated with CBP (ß = -0.29, P < 0.01). CONCLUSION: When CBP are identified, parenting skills, mental health status and parental relationships should be considered along with the possibility of developmental disorders in the development of interventions.

Green light-emitting diode phototherapy for neonatal hyperbilirubinemia: Randomized controlled trial.

BACKGROUND: The main photochemical pathway in phototherapy for neonatal hyperbilirubinemia is the production and elimination (in bile or urine) of cyclobilirubin, which is a structural photoisomer of bilirubin, and which is most efficiently produced by green light. Green light-emitting diode (LED) phototherapy, however, has not been evaluated in the clinical setting because it is not recommended in American Academy of Pediatrics guidelines. We therefore compared the efficacy of green LED phototherapy and blue LED phototherapy in patients with neonatal hyperbilirubinemia. METHODS: In this prospective randomized controlled trial, neonates with hyperbilirubinemia were randomly allocated to a green LED or blue LED phototherapy group. Both groups underwent 24 h of phototherapy, and blood was sampled before and after 24 h of phototherapy. Total serum bilirubin (TSB) was measured using enzymatic methods and bilirubin photoisomers were measured on high-performance liquid chromatography. RESULTS: Thirty-four infants were randomized (green, n = 16; blue, n = 18). TSB decreased significantly from 15.3 ± 1.5 to 13.9 ± 1.5 mg/dL in the green LED group (P < 0.01) and from 16.2 ± 1.3 to 14.5 ± 1.7 mg/dL in the blue LED group (P < 0.01) after 24 h of phototherapy. No significant difference was found in TSB reduction after phototherapy between the groups. CONCLUSIONS: Both light sources produced a significant reduction in TSB, indicating clinical effectiveness.

Effect of psychotropic drugs on fetal behavior in the third trimester of pregnancy.

AIM: To assess the effect of psychotropic drugs on fetal behavior using four-dimensional (4D) ultrasound in the third trimester of pregnancy. METHODS: Fetal behavior was assessed using Kurjak's antenatal neurodevelopmental test (KANET) using 4D ultrasound between 28 and 36 weeks of gestation. Thirty healthy (control group) and 10 psychotropic-drug-administered pregnant (case group) women were studied. The total value of the KANET score and values of each parameter (eight parameters) were compared between the two groups. RESULTS: The total KANET score was normal (except for one fetus in the case group: total score of 9) in both groups, and there was no significant difference in the total KANET score. When individual KANET parameters were compared, no significant differences were noted in any of the eight parameters. CONCLUSION: Our results showed that there is no difference in fetal behavior between fetuses of normal pregnant women and those of psychotropic-drug-administered pregnant women in the third trimester of pregnancy. These results suggest that psychotropic drugs may not affect fetal behavioral development in utero. However, the data and their interpretation in the present study should be taken with some degree of caution because of the small number of subjects studied. Further studies involving a larger sample size are needed to assess the effect of psychotropic drugs on fetal neurobehavior during pregnancy.

Prediction of postnatal developmental disabilities using the antenatal fetal neurodevelopmental test: KANET assessment.

Objective To assess the usefulness of the antenatal fetal neurodevelopmental test for the prediction of postnatal developmental disabilities. Methods Fetal behavior was assessed with Kurjak's antenatal neurodevelopmental test (KANET) using four-dimensional ultrasound between 28 and 38 weeks of gestation. A score range of 0-5 was characterized as abnormal, from 6 to 9 was considered borderline, and 10-16 was normal. After birth, follow-up was conducted for at least 2 years in all fetuses. Results There were 337 normal (95.47%) and 16 borderline (4.53%) cases among the 353 cases studied, whereas there was no abnormal case. Five cases with postnatal developmental disabilities (one case of Werdig-Hoffmann disease diagnosed just after delivery, one case of autism spectrum disorder diagnosed at 24 months, one case of Ullrich congenital muscular dystrophy diagnosed at 9 months and two cases of developmental disorders diagnosed at age 3 and 18 months) were noted among the 337 normal cases (1.48%), whereas three cases with developmental disabilities (one case of motor development delay diagnosed at 6 months, one case of Duchenne muscular dystrophy diagnosed at 18 months and one case of autism spectrum disorder diagnosed at age 30 months) were found among the 16 borderline cases (18.75%). There was a significant difference in the prevalence of postnatal developmental disabilities between the normal and borderline KANET groups (P<0.001). Conclusion Our results suggest that the KANET assessment may be a useful diagnostic modality for the prediction of postnatal developmental disabilities.

Prolonged maternal separation attenuates BDNF-ERK signaling correlated with spine formation in the hippocampus during early brain development.

Maternal separation (MS) is known to affect hippocampal function such as learning and memory, yet the molecular mechanism remains unknown. We hypothesized that these impairments are attributed to abnormities of neural circuit formation by MS, and focused on brain-derived neurotrophic factor (BDNF) as key factor because BDNF signaling has an essential role in synapse formation during early brain development. Using rat offspring exposed to MS for 6 h/day during postnatal days (PD) 2-20, we estimated BDNF signaling in the hippocampus during brain development. Our results show that MS attenuated BDNF expression and activation of extracellular signal-regulated kinase (ERK) around PD 7. Moreover, plasticity-related immediate early genes, which are transcriptionally regulated by BDNF-ERK signaling, were also reduced by MS around PD 7. Interestingly, detailed analysis revealed that MS particularly reduced expression of BDNF gene and immediate early genes in the cornu ammonis 1 (CA1) of hippocampus at PD 7. Considering that BDNF-ERK signaling is involved in spine formation, we next evaluated spine formation in the hippocampus during the weaning period. Our results show that MS particularly reduced mature spine density in proximal apical dendrites of CA1 pyramidal neurons at PD 21. These results suggest that MS could attenuate BDNF-ERK signaling during primary synaptogenesis with a region-specific manner, which is likely to lead to decreased spine formation and maturation observed in the hippocampal CA1 region. It is speculated that this incomplete spine formation during early brain development has an influence on learning capabilities throughout adulthood.