Grafting Neural Stem and Progenitor Cells Into the Hippocampus of Juvenile, Irradiated Mice Normalizes Behavior Deficits.

The pool of neural stem and progenitor cells (NSPCs) in the dentate gyrus of the hippocampus is reduced by ionizing radiation. This explains, at least partly, the learning deficits observed in patients after radiotherapy, particularly in pediatric cases. An 8 Gy single irradiation dose was delivered to the whole brains of postnatal day 9 (P9) C57BL/6 mice, and BrdU-labeled, syngeneic NSPCs (1.0 × 105 cells/injection) were grafted into each hippocampus on P21. Three months later, behavior tests were performed. Irradiation impaired novelty-induced exploration, place learning, reversal learning, and sugar preference, and it altered the movement pattern. Grafting of NSPCs ameliorated or even normalized the observed deficits. Less than 4% of grafted cells survived and were found in the dentate gyrus 5 months later. The irradiation-induced loss of endogenous, undifferentiated NSPCs in the dentate gyrus was completely restored by grafted NSPCs in the dorsal, but not the ventral, blade. The grafted NSPCs did not exert appreciable effects on the endogenous NSPCs; however, more than half of the grafted NSPCs differentiated. These results point to novel strategies aimed at ameliorating the debilitating late effects of cranial radiotherapy, particularly in children.

Carbamylated Erythropoietin Decreased Proliferation and Neurogenesis in the Subventricular Zone, but Not the Dentate Gyrus, After Irradiation to the Developing Rat Brain.

Cranial radiotherapy for pediatric brain tumors causes progressive, debilitating late effects, including cognitive decline. Erythropoietin (EPO) has been shown to be neuroprotective and to promote neuroregeneration. Carbamylated erythropoietin (CEPO) retains the protective properties of EPO but is not erythrogenic. To study the effects of CEPO on the developing brain exposed to radiotherapy, a single irradiation (IR) dose of 6 Gy was administered to the brains of postnatal day 9 (P9) rats, and CEPO (40 µg/kg s.c.) was injected on P8, P9, P11, P13, and P15. To examine proliferation, 5-Bromo-2-deoxyuridine (BrdU) was injected on P15, P16, and P17. CEPO administration did not affect BrdU incorporation in the granule cell layer (GCL) of the hippocampus or in the subventricular zone (SVZ) as quantified 7 days after the last BrdU injection, whereas IR decreased BrdU incorporation in the GCL and SVZ by 63% and 18%, respectively. CEPO did not affect BrdU incorporation in the GCL of irradiated brains, although it was reduced even further (to 31%) in the SVZ. To evaluate the effect of CEPO on neurogenesis, BrdU/doublecortin double-positive cells were quantified. CEPO did not affect neurogenesis in non-irradiated brains, whereas IR decreased neurogenesis by 58% in the dentate gyrus (DG) but did not affect it in the SVZ. In the DG, CEPO did not affect the rate of neurogenesis following IR, whereas in the SVZ, the rate decreased by 30% following IR compared with the rate in vehicle-treated rats. Neither CEPO nor IR changed the number of microglia. In summary, CEPO did not promote neurogenesis in non-irradiated or irradiated rat brains and even aggravated the decreased neurogenesis in the SVZ. This raises concerns regarding the use of EPO-related compounds following radiotherapy.

Perioperative Management Center (PERIO) for Neurosurgical Patients.

Perioperative management is critical for positive neurosurgical outcomes. In order to maintain safe and authentic perioperative management, a perioperative management center (PERIO) was introduced to patients of our Neurosurgery Department beginning in June 2014. PERIO involves a multidisciplinary team consisting of anesthesiologists, dentists/dental hygienists/technicians, nurses, physical therapists, pharmacists, and nutritionists. After neurosurgeons decide on the course of surgery, a preoperative evaluation consisting of blood sampling, electrocardiogram, chest X-ray, and lung function test was performed. The patients then visited the PERIO clinic 7-14 days before surgery. One or two days before surgery, the patients without particular issues enter the hospital and receive a mouth cleaning one day before surgery. After surgery, postoperative support involving eating/swallowing evaluation, rehabilitation, and pain control is provided. The differences in duration from admission to surgery, cancellation of surgery, and postoperative complications between PERIO and non-PERIO groups were examined. Eighty-five patients were enrolled in the PERIO group and 131 patients in the non-PERIO group. The duration from admission to surgery was significantly decreased in the PERIO group (3.6 ± 0.3 days), compared to that in the non-PERIO group (4.7 ± 0.2 days). There was one cancelled surgery in the PERIO group and six in the non-PERIO group. Postoperative complications and the overall hospital stay did not differ between the two groups. The PERIO system decreased the duration from admission to surgery, and it is useful in providing high-quality medical service, although the system should be improved so as not to increase the burden on medical staff.

Suppressive effect of poly-gamma-glutamate on SOS response of Salmonella typhimurium induced by chemical mutagens.

We studied the suppressive effect of poly-gamma-glutamate (PGA) on the SOS response of Salmonella typhimurium induced by several direct [furylframide, AF-2; N-methyl-N'-nitro-N-nitrosoguanidine, MNNG; and 4-nitroquinoline 1-oxide, 4NQO] and indirect [3-amino-1-methyl-5H-pyrido-(4,3-b) indole, Trp-P-2; 2-amino-3-methylimidazo (4,5-f) quinoline, IQ; and 2-amino-3,8-dimethylimidazo (4,5-f) quinoxaline, MeIQx] mutagens. PGA preparations with average molecular masses of 50, 2000, 4000, 6000, and 8000 kDa from Bacillus subtilis (chungkookjang) were used. When we used PGA Na salt with a molecular mass of 4000 kDa, the suppression rate increased with increasing PGA concentration; 3% PGA showed 80-90% suppression irrespective of the type of chemical mutagen. PGA preparations with molecular masses of 50 kDa and more than 6000 kDa were less effective. Glutamate and acidic polymers such as carboxymethylcellulose and xanthan gum showed lower suppressive effects than PGA. PGA proved to have high antimutagenic activity.

Delayed neurological signs following isolated parasagittal injury in asphyxia at term.

BACKGROUND: Parasagittal cerebral injury is a type of cerebral injury in term infants, which is characterized by the predominant injury of the arterial border zones of the anterior, middle and posterior cerebral arteries, however its early clinical manifestation is mostly unclear. AIM: To understand early clinical features of parasagittal cerebral injury. METHODS: The clinical details of 18 newborn infants who were diagnosed as having parasagittal cerebral injury on magnetic resonance imaging (MRI). Eleven infants had localized injury within parasagittal regions ("Limited" group), 7 infants had diffuse extensive injury involving the deep gray matter and/or periventricular white matter ("Extensive" group). These infants were compared with 9 infants with perinatal asphyxia without MRI abnormalities ("Normal" group). RESULTS: There was no significant difference in the rate of cardiotocographic abnormalities, low Apgar scores, low blood pH and base excess, and the requirement for mechanical ventilation among three groups. Compared with the Normal group, fewer infants in the Limited group developed neonatal encephalopathy within an hour after birth. Neonatal seizures were more frequent in the Limited and the Extensive groups. Hepatic and/or renal dysfunction was more often observed in the Limited group. Cerebral palsy and/or mental retardation were common in the Extensive group. Electro-cortical depression was more in the Extensive group. Progressive suppression of electro-cortical activity was common within infants in the Limited group (33%) and the Extensive group (60%). CONCLUSION: Infants with parasagittal cerebral injury developed serious neurological abnormalities despite less serious physiological and neurological manifestation shortly after birth, suggesting the importance of careful longitudinal observation of asphyxiated infants.

Simple improvement in freeze-tolerance of bakers' yeast with poly-gamma-glutamate.

We examined the effect of poly-gamma-glutamate (PGA) on the freeze-tolerance of four types of commercial bakers' yeast (freeze-tolerant, osmotic-tolerant, low-temperature-sensitive, and ordinary bakers' yeasts). The survival ratio of ordinary bakers' yeast cells frozen at -30 degrees C for 3 d in a medium (0.5% yeast extract, 0.5% peptone, and 2% glucose: YPD medium) was improved by adding more than 1% PGA to the medium; the survival ratio increased from about 10% to more than 70%. All PGA preparations, which differed in average molecular mass (50, 2,000, 4,000, 6,000, 8,000, and 10,000 kDa), showed a similar cryoprotecive effect on the cells. Similar results were also obtained with other types of bakers' yeast, sake yeast and beer yeast. When the four types of bakers' yeast cell were frozen at -30 degrees C for 3 d in dough supplemented with more than 1% PGA, the cells (after freezing and thawing) showed higher leavening ability than those frozen in dough without PGA, irrespective of the molecular mass of PGA. Thus, PGA appears to protect bakers' yeast from lethal freeze injury, leading to a high leavening ability after freezing and thawing. PGA did not decrease the original leavening ability of the bakers' yeast, and was not decomposed by the yeast cells. PGA suppressed the decrease in leavening ability during a prolonged fermentation time, probably because PGA adsorbed inhibitory metabolites accumulated in the dough. PGA could prove useful for improving the freeze-tolerance of bakers' yeast by its addition to dough.

Intracellular glycerol influences resistance to freeze stress in Saccharomyces cerevisiae: analysis of a quadruple mutant in glycerol dehydrogenase genes and glycerol-enriched cells.

Glycerol is well known as a cryoprotectant similar to trehalose. However, there is little information about the effects of intracellular glycerol on the freeze-thaw stress tolerance of yeast. Through analysis of a quadruple-knockout mutant of glycerol dehydrogenase genes (ara1 Delta gcy1 Delta gre3 Delta ypr1 Delta) in Saccharomyces cerevisiae, we revealed that the decrease in glycerol dehydrogenase activity led to increased levels of intracellular glycerol. We also found that this mutant showed higher tolerance to freeze stress than wild type strain W303-1A. Furthermore, we demonstrated that intracellular-glycerol-enriched cells cultured in glycerol medium acquire tolerance to freeze stress and retain high leavening ability in dough even after frozen storage for 7 days. These results suggest the possibility of using intracellular-glycerol-enriched cells to develop better frozen dough.