Tomoaki Ioroi

Effects of hypoxia and reoxygenation on nitric oxide production and cerebral blood flow in developing rat striatum

We investigated the role of nitric oxide (NO) in the regulation of regional cerebral blood flow (rCBF) during hypoxia and reoxygenation in developing rat striatum. The subjects were urethane-anesthetized 7- and 14-d-old rats. After 120 min of baseline measurements, the rats received an i.p. injection of either saline (as a control) or an NO synthase inhibitor,N- nitro-l-arginine methyl ester (l-NAME, 30 mg/kg) 30 min before hypoxia. Then they were subjected to a 60-min hypoxia in 8% O2, followed by a 60-min recovery in 21% O2. rCBF and NO concentration in the striatum were measured by laser Doppler flowmetry and an NO electrode throughout the experimental period. In the controls, rCBF decreased to 93± 3% of baseline during hypoxia and increased to 124 ± 3% of baseline during reoxygenation in 7-d-old rats (n = 13), whereas rCBF increased during both hypoxia and reoxygenation in 14-d-old rats to 125± 6% and 168 ± 6% of baseline, respectively (n = 17). l-NAME attenuated the hyperemic response to hypoxia/reoxygenation in both ages(n = 11, in each age). Striatal NO production increased during hypoxia and reoxygenation in both ages, but the increase was significantly less in 7-d-old than in 14-d-old rats. The NO increase was associated with the increase in rCBF, and both were attenuated by l-NAME. We speculate that NO release during hypoxia/reoxygenation modulates rCBF. The immature young rat brain may have less capacity to activate NO production than the more developed brain.

A 12p13 GRIN2B deletion is associated with developmental delay and macrocephaly

N-methyl D-aspartate receptor subtype 2B (GluN2B), encoded by GRIN2B, is one of the components of the N-methyl D-aspartate receptor protein. Aberrations in GRIN2B have been reported to be responsible for various types of neurodevelopmental disorders. We report a Japanese boy with an ~2 Mb interstitial deletion in 12p13 involving the entire GRIN2B gene, who presented with intellectual disability, motor developmental delay and marked macrocephaly.

A Fatal Case of Congenital Langerhans Cell Histiocytosis with Disseminated Cutaneous Lesions in a Premature Neonate.

Background. The outcome of neonates with congenital cutaneous Langerhans cell histiocytosis (LCH) is variable. Observations. We report a case of LCH in a female premature neonate born at 33-week gestation. She had disseminated cutaneous lesions, which consisted of hemorrhagic papules and vesicles, with sparse healthy skin areas, and the hands and feet were contracted with scarring and blackened. She was in respiratory failure although no apparent pulmonary or bone lesions on X-rays were noted. Skin biopsy confirmed a diagnosis of LCH due to observation of CD1a+ Langerhans cells, which lacked expression of E-cadherin and CD56. The patient died 57 hours after birth. Conclusions. Based on this case and the literature survey, the outcome of premature babies with congenital cutaneous LCH lesions is noted to be unfavorable, with the majority of such cases suffering from multisystem disease.

Evaluation index for asymmetric ventricular size on brain magnetic resonance images in very low birth weight infants

OBJECTIVE Asymmetric ventriculomegaly is often evident on brain magnetic resonance imaging (MRI) in very low birth weight infants (VLBWI) and is interpreted as white matter injury. However, no evaluation index for asymmetric left-right and anterior-posterior ventricular sizes has been established. METHODS In this retrospective multicenter cohort study, brain T2-weighted MRI was performed at term-equivalent ages in 294 VLBWI born between 2009 and 2011. The value of a lateral ventricular index (LVI) to evaluate asymmetric ventricular size, as well as the relationship between the LVI value and walking at a corrected age of 18 months was investigated. At the level of the foramen of Monro in a horizontal slice, asymmetry between the left and right sides and between the anterior and posterior horns was identified by the corrected width and was detected by a low concordance rate and κ statistic value. An LVI representing the sum of the widths of the four horns of the lateral ventricle corrected for cerebral diameter was devised. RESULTS Asymmetric left-right and anterior-posterior ventricular sizes were confirmed. The LVI value was significantly higher in the non-walking VLBWI group (n = 39) than in the walking VLBWI group (n = 255; 18.2 vs. 15.8, p = 0.02). An LVI cut-off value of 21.5 was associated with non-walking. Multivariate analysis revealed that an LVI value >21.5 was an independent predictor of walking disability at the corrected age of 18 months (odds ratio 2.56, p = 0.008). CONCLUSIONS The LVI value calculated via MRI may predict walking disability at a corrected age of 18 months in VLBWI.

Effect of a Nitric Oxide Synthase Inhibitor on Striatal Blood Flow during Hypoxia and Reoxygenation in Immature Rats. † 913

Effect of a Nitric Oxide Synthase Inhibitor on Striatal Blood Flow during Hypoxia and Reoxygenation in Immature Rats. † 913

Effect of Insulin-Induced Hypoglycemia on Cerebral Blood Flow and Nitric Oxide Level in Immature Rat Striatum. † 914

Effect of Insulin-Induced Hypoglycemia on Cerebral Blood Flow and Nitric Oxide Level in Immature Rat Striatum. † 914

DIRECT MEASUREMENT OF NITRIC OXIDE PRODUCTION DURING HYPOXIA AND REOXYGENATION IN DEVELOPING RAT STRIATUM. ▴ 1287

The aim of the present study was to obtain direct evidence of nitric oxide(NO) production in developing rat striatum during hypoxia and reoxygenation by using a NO-selective amperometric microsensor (NO-501, Inter Medical Co., Nagoya, Japan). The study was carried out in urethane-anesthetized 7-day-old and 14-day-old rats (n=6, in each group). The microsensor was calibrated to NO with S-nitroso-N-acetyl-DL-penicillamine before experiment. A current of 100 pA approximately corresponded to NO concentration of 20 nM. We inserted the working electrode into the right striatum and monitored NO response continuously throughout the experiment. Following stabilization, rats were subjected to 60-min hypoxia with 8% O2 and the subsequent 60-min reoxygenation with 21% O2. In 7-day-old rats, we observed a gradual increase in NO release by 101±44 pA in the course of hypoxia and a secondary increase by 178±62 pA during reoxygenation. In 14-day-old rats, the amount of an increase of NO released in response to hypoxia and that of another increase induced by reoxygenation were 426±136 and 430±139 pA, respectively. They were significantly greater than those in 7-day-old rats(p<0.05). Pretreatment with a NO synthase inhibitor,N-nitro-L-arginine methyl ester (5 mg/kg, i.p.) remarkably attenuated NO release during hypoxia and reoxygenation at both ages. The present study demonstrates that the NO microelectrode can detect nanomolar levels of NO released in developing brain. Smaller NO release induced by hypoxia and reoxygenation in younger rats may indicate that immature brain has less ability to activate NO synthase than more developed brain. (Funded by a Grant-in Aid from the Ministry of Education and Science of Japan)