Tetsuo Hattori

Administration of umbilical cord blood cells transiently decreased hypoxic-ischemic brain injury in neonatal rats.

This study aimed to investigate whether the administration of mononuclear cells derived from human umbilical cord blood cells (UCBCs) could ameliorate hypoxic-ischemic brain injury in a neonatal rat model. The left carotid arteries of 7-day-old rats were ligated, and the rats were then exposed to 8% oxygen for 60 min. Mononuclear cells derived from UCBCs using the Ficoll-Hypaque technique were injected intraperitoneally 6 h after the insult (1.0 × 107 cells). Twenty-four hours after the insult, the number of cells positive for the oxidative stress markers 4-hydroxy-2-nonenal and nitrotyrosine, in the dentate gyrus of the hippocampus in the UCBC-treated group, decreased by 36 and 42%, respectively, compared with those in the control group. In addition, the number of cells positive for the apoptosis markers active caspase-3 and apoptosis-inducing factor decreased by 53 and 58%, respectively. The number of activated microglia (ED1-positive cells) was 51% lower in the UCBC group compared with the control group. In a gait analysis performed 2 weeks after the insult, there were no significant differences among the sham-operated, control and UCBC groups. An active avoidance test using a shuttle box the following week also revealed no significant differences among the groups. Neither the volumes of the hippocampi, corpus callosum and cortices nor the numbers of neurons in the hippocampus were different between the UCBC and control groups. In summary, a single intraperitoneal injection of UCBC-derived mononuclear cells 6 h after an ischemic insult was associated with a transient reduction in numbers of apoptosis and oxidative stress marker-positive cells, but it did not induce long-term morphological or functional protection. Repeated administration or a combination treatment may be required to achieve sustained protection.

Effect of hospital volume on the mortality of congenital diaphragmatic hernia in Japan

During the last decade, new supportive modalities and new therapeutic strategies to treat congenital diaphragmatic hernia (CDH) have been introduced. In Japan, the large number of hospitals prevents centralizing infants with CDH in tertiary centers. The aim of this study was to evaluate the correlations between the number of CDH patients, survival rates, and the current strategies employed to treat CDH at the individual hospitals.

Nationwide surveillance of circulatory collapse associated with levothyroxine administration in very‐low‐birthweight infants in Japan

Background:  Although the administration of levothyroxine sodium (LT4) to premature infants had been considered safe, several cases of late‐onset circulatory collapse (LCC) following the administration of LT4 in very‐low‐birth‐weight (VLBW) infants have been reported in Japan since 2008. This study was performed to investigate the incidence of LCC associated with the administration of LT4 to VLBW infants.

Diffusion-weighted magnetic resonance imaging in infants with periventricular leukomalacia.

OBJECTIVE We examined diffusion-weighted magnetic resonance imaging (DWI) findings in periventricular leukomalacia (PVL) and then evaluated the relationship between the mean apparent diffusion coefficient (ADC) values and the region and severity of PVL. METHODS Between April 2006 and July 2007, 98 infants at gestational ages between 27 and 33 weeks were enrolled in the study. DWI was performed during the first week of life when electroencephalography indicated PVL. The mean ADC values were evaluated using regions of interest drawn manually in the periventricular white matter, posterior limbs of internal capsules (PLICs), and various regions of the brain. RESULTS DWI was performed in three of four infants with PVL indicated on electroencephalography. All had decreased diffusivity in the anterior to posterior white matter despite a predominance in the posterior white matter. DWI abnormalities were also observed in the corpus callosum and PLICs and were more broadly distributed in the brain than those detected by later conventional MRI. In the PLICs, the changes in the ADC values were correlated with the severity of the PVL. CONCLUSION The DWI findings provided additional information regarding PVL. Among the findings, the association of the presence of decreased diffusivity in the corticospinal tract with later motor impairment was the most interesting.

Spontaneous spinal epidural hematoma in an infant with undiagnosed hemophilia A

Major symptoms of patients with hemophilia are subcutaneous hemorrhage, intramuscular hemorrhage, and intra-articular hemorrhage. Moreover, central nervous system (CNS) hemorrhage is sometimes seen in hemophilia. This is a serious condition, and appropriate diagnosis and treatment are necessary for a good outcome. Spinal epidural hematoma (SEH) is a rare complication in CNS hemorrhage, compared to the incidence of intracranial hemorrhage. Once established, SEH continuously compresses the spinal cord and nerve roots, and the patient shows neurological abnormalities such as sensory disturbance, paralysis of the extremities or urination disturbance. We encountered an unusual case in a patient with severe hemophilia A, in which SEH was presented as an initial symptom, and it was treated successfully with factor VIII replacement. Magnetic resonance imaging (MRI) findings were reported previously. In this article, we report the detailed clinical course and review the relevant literature.

Prolonged EEG depression in term and near-term infants with hypoxic ischemic encephalopathy and later development of West syndrome

Purpose:  This study was performed to clarify the relationship between prolonged depression of electroencephalography (EEG) in term and near‐term infants with hypoxic ischemic encephalopathy (HIE) and the later development of West syndrome (WS).

Dedifferentiated Fat Cells as a Novel Source for Cell Therapy to Target Neonatal Hypoxic-Ischemic Encephalopathy

Neonatal hypoxic-ischemic (HI) encephalopathy (HIE) remains a major cause of mortality and persistent neurological disabilities in affected individuals. At present, hypothermia is considered to be the only applicable treatment option, although growing evidence suggests that cell-based therapy might achieve better outcomes. Dedifferentiated fat (DFAT) cells are derived from mature adipocytes via a dedifferentiation strategy called ceiling culture. Their abundance and ready availability might make them an ideal therapeutic tool for the treatment of HIE. In the present study, we aimed to determine whether the outcome of HIE can be improved by DFAT cell treatment. HI injury was achieved by ligating the left common carotid artery in 7-day-old rat pups, followed by 1-h exposure to 8% O2. Subsequently, the severity of damage was assessed by diffusion-weighted magnetic resonance imaging to assign animals to equivalent groups. 24 h after hypoxia, DFAT cells were injected at 105 cells/pup into the right external jugular vein. To evaluate brain damage in the acute phase, a group of animals was sacrificed 48 h after the insult, and paraffin sections of the brain were stained to assess several acute injury markers. In the chronic phase, the behavioral outcome was measured by performing a series of behavioral tests. From the 24th day of age, the sensorimotor function was examined by evaluating the initial forepaw placement on a cylinder wall and the latency to falling from a rotarod treadmill. The cognitive function was tested with the novel object recognition (NOR) test. In vitro conditioned medium (CM) prepared from cultured DFAT cells was added at various concentrations to neuronal cell cultures, which were then exposed to oxygen-glucose deprivation (OGD). The number of cells that stained positive for the apoptosis marker active caspase-3 decreased by 73 and 52% in the hippocampus and temporal cortex areas of the brain, respectively, in the DFAT-treated pups. Similarly, the numbers of ED-1-positive cells (activated microglia) decreased by 66 and 44%, respectively, in the same areas in the DFAT-treated group. The number of cells positive for the oxidative stress marker 4-hydroxyl-2-nonenal decreased by 68 and 50% in the hippocampus and the parietal cortex areas, respectively, in the DFAT-treated group. The HI insult led to a motor deficit according to the rotarod treadmill and cylinder test, where it significantly affected the vehicle group, whereas no difference was confirmed between the DFAT and sham groups. However, the NOR test indicated no significant differences between any of the groups. DFAT treatment did not reduce the infarct volume, which was confirmed immunohistochemically. According to in vitro experiments, the cell death rates in the DFAT-CM-treated cells were significantly lower than those in the controls when DFAT-CM was added 48 h prior to OGD. The treatment effect of adding DFAT-CM 24 h prior to OGD was also significant. Our results indicate that intravenous injection with DFAT cells is effective for ameliorating HI brain injury, possibly via paracrine effects.

Carbohydrate and Energy Metabolism in the Brain of Rats With Thromboxane A2-Induced Fetal Growth Restriction

Fetal growth restriction (FGR) remains a cause of perinatal brain injury, sometimes leading to neurological and intellectual impairment. Although the mechanisms and pathophysiology of CNS injuries have not been elucidated completely, it is possible carbohydrate and energy metabolism may have an important role in the FGR brain. In this study, FGR was induced in rats by administration of synthetic thromboxane A2 (STA2). Pups were delivered by cesarean section. After killing, samples were obtained from the fetuses of both control and FGR rats for evaluation of carbohydrate and energy metabolism in brain tissue. Lactate and pyruvate levels in brain were reduced significantly in the FGR group. Glucose content in brain tissue tended to be increased in the FGR group. In contrast, glycogen content in brain tissue tended to be lower in the FGR group. However, these differences in glucose and glycogen content did not reach statistical significance. Brain high-energy reserves, including ATP, ADP, AMP, and phosphocreatine (P-Cr), were similar in the control and FGR groups. Gluconeogenesis compensated for chronic fetal hypoxia and decreased glycogen storage. Energy metabolism in the FGR brain is likely to be disrupted as a consequence of lower reserves of energy substrates.

Prognostic factors of hydrops fetalis with pleural effusion

Hydrops fetalis (HF) has a low survival rate, particularly in the case of preterm birth. In addition, the severity index of HF has not been fully investigated yet. The aim of this study was to clarify the prognostic factors of HF with pleural effusion.

Apneas observed in trisomy 18 neonates should be differentiated from epileptic apneas

Many children with trisomy 18 have apneas from the neonatal period. It has been reported that some children with trisomy 18 have epilepsy, including epileptic apneas. However, no previous report has described epileptic apneas in trisomy 18 neonates. We retrospectively reviewed the clinical records of neonates with trisomy 18 who were born at Anjo Kosei Hospital between July 2004 and October 2013 and investigated whether they had epileptic apneas during the neonatal period and whether antiepileptic drugs (AEDs) were effective for treating them. We identified 16 patients with trisomy 18. Nine patients who died within 3 days of birth were excluded. Five of the remaining seven patients had apneas. All five patients underwent electroencephalograms (EEGs) to assess whether they suffered epileptic apneas. Three of the five patients had EEG‐confirmed seizures. In two patients, the apneas corresponded to ictal discharges. In one patient, ictal discharges were recorded when she was under mechanical ventilation, but no ictal discharges that corresponded to apneas were recorded after she was extubated. AEDs were effective for treating the apneas and stabilizing the SpO2 in all three patients. Among neonates with trisomy 18 who lived longer than 3 days, three of seven patients had EEG‐confirmed seizures. AEDs were useful for treating their epileptic apneas and stabilizing their SpO2. Physicians should keep epileptic apneas in mind when treating apneas in neonates with trisomy 18.