ABSTRACT
Many previous studies have shown reduced glucose uptake in the ischemic brain. In contrast, in a permanent unilateral common carotid artery occlusion (UCCAO) mouse model, our pilot experiments using 18F-fluorodeoxyglucose positron emission tomography (FDG PET) revealed that a subset of mice exhibited conspicuously high uptake of glucose in the ipsilateral hemisphere at 1 week post-occlusion (asymmetric group), whereas other mice showed symmetric uptake in both hemispheres (symmetric group). Thus, we aimed to understand the discrepancy between the two groups. Cerebral blood flow and histological/metabolic changes were analyzed using laser Doppler flowmetry and immunohistochemistry/Western blotting, respectively. Contrary to the increased glucose uptake observed in the ischemic cerebral hemisphere on FDG PET (p<0.001), cerebral blood flow tended to be lower in the asymmetric group than in the symmetric group (right to left ratio [%], 36.4±21.8 vs. 58.0±24.8, p=0.059). Neuronal death was observed only in the ischemic hemisphere of the asymmetric group. In contrast, astrocytes were more activated in the asymmetric group than in the symmetric group (p<0.05). Glucose transporter-1, and monocarboxylate transporter-1 were also upregulated in the asymmetric group, compared with the symmetric group (p<0.05, respectively). These results suggest that the increased FDG uptake was associated with relatively severe ischemia, and glucose transporter-1 upregulation and astrocyte activation. Glucose metabolism may thus be a compensatory mechanism in the moderately severe ischemic brain.
ABSTRACT
Survival and migration of transplanted neural stem cells (NSCs) are prerequisites for therapeutic benefits in spinal cord injury. We have shown that survival of NSC grafts declines after transplantation into the injured spinal cord, and that combining treadmill training (TMT) enhances NSC survival via insulin-like growth factor-1 (IGF-1). Here, we aimed to obtain genetic evidence that IGF-1 signaling in the transplanted NSCs determines the beneficial effects of TMT. We transplanted NSCs heterozygous (+/−) for Igf1r, the gene encoding IGF-1 receptor, into the mouse spinal cord after injury, with or without combining TMT. We analyzed the influence of genotype and TMT on locomotor recovery and survival and migration of NSC grafts. In vitro experiments were performed to examine the potential roles of IGF-1 signaling in the migratory ability of NSCs. Mice receiving +/− NSC grafts showed impaired locomotor recovery compared with those receiving wild-type (+/+) NSCs. Locomotor improvement by TMT was more pronounced with +/+ grafts. Deficiency of one allele of Igf1r significantly reduced survival and migration of the transplanted NSCs. Although TMT did not significantly influence NSC survival, it substantially enhanced the extent of migration for only +/+ NSCs. Cultured neurospheres exhibited dynamic motility with cytoplasmic protrusions, which was regulated by IGF-1 signaling. IGF-1 signaling in transplanted NSCs may be essential in regulating their survival and migration. Furthermore, TMT may promote NSC graft-mediated locomotor recovery via activation of IGF-1 signaling in transplanted NSCs. Dynamic NSC motility via IGF-1 signaling may be the cellular basis for the TMT-induced enhancement of migration.
Subject(s)
Animals , Mice , Alleles , Cytoplasm , Genotype , In Vitro Techniques , Insulin-Like Growth Factor I , Neural Stem Cells , Receptor, IGF Type 1 , Spinal Cord Injuries , Spinal Cord , TransplantsABSTRACT
BACKGROUND AND PURPOSE: N-methyl-D-aspartate (NMDA)-mediated neurotoxicity and oxidative stress have been implicated in the etiology of amyotrophic lateral sclerosis (ALS). Memantine is a low-affinity, noncompetitive NMDA receptor antagonist that may protect against motor neuron degeneration. METHODS: Thirty transgenic mice expressing the G93A SOD1 mutation were randomly divided into control, low-dose memantine (30 mg/kg/day), and high-dose memantine (90 mg/kg/day) groups, with memantine supplied daily with drinking water beginning at 75 days of age. Body weight, survival, and behavioral performances including a rotarod test, paw grip endurance, and hindlimb extension reflex were assessed in the control and memantine-diet groups. RESULTS: Clinical symptoms were evident in the G93A transgenic mice by 11 weeks of age. Memantine was tolerated well. Compared to control, mice treated with memantine performed better in the rotarod test and hindlimb extension reflex. Moreover, low-dose memantine treatment significantly prolonged the survival of the transgenic mice relative to control mice (141 vs 134 days, p<0.05). CONCLUSIONS: These findings suggest that memantine, even when administered at the time of symptom onset, has beneficial effects on patients with ALS.
Subject(s)
Animals , Humans , Mice , Administration, Oral , Amyotrophic Lateral Sclerosis , Body Weight , Drinking Water , Hand Strength , Hindlimb , Memantine , Mice, Transgenic , Motor Neurons , N-Methylaspartate , Oxidative Stress , Reflex , Rotarod Performance TestABSTRACT
Primary carcinoma of the fallopian tube is a rare malignancy of the female genital tract and infrequently diagnosed before an operation. The majority of patients have extensive disease at the time of diagnosis. We have experienced incidentally a case of a carcinoma of the fallopian tube coexisting with a benign cystic teratoma of the ovary in a 25-year-old woman. We report this case with a brief review of literatures.
Subject(s)
Adult , Female , Humans , Adenocarcinoma, Papillary/pathology , Fallopian Tube Neoplasms/pathology , Neoplasms, Multiple Primary/pathology , Ovarian Neoplasms/pathology , Teratoma/pathologyABSTRACT
Many researchers report that the measurement of urine calcium concentration during antenatal period is helpful in prediction of having preeclampsia,but some don`t. The purpose of this clinical study is to evaluate the relationship of low calcium level in urine and the develpoment of preeclampsia, and effects of other variables. 24hour urine were collected and measured for the concentration of calcium and creatinine from 769 pregnant women who visited our department of obstetrics at Young-Dong Severeance hospital, Yonsei university medical college for antenatal care from March 1, 1993 to May 31, 1996. One group of 41 women developed preeclampsia and the other didn`t. There were no diffrences in ages and gestational age at urine collection between two groups, but a group with preeclampsia had an increased mean arterial blood pressure. There were signiificant difference in calcium concentration in urine and ratios of concentration of calcium and creatinine from urine collected between gestational ages of 25 weeks and 32 weeks and also in those women younger than 25 years old and their first pregnancy. Our study suggests that the measure ment of calcium level and ratios of urine calcium concentration and creatinine concentration at gestational ages between 25 weeks and 32 weeks in women younger than 25 year old with their first pregnancy is quite helpful inpredicting the develpoment of preeclampsia.
Subject(s)
Adult , Female , Humans , Pregnancy , Arterial Pressure , Calcium , Creatinine , Gestational Age , Obstetrics , Pre-Eclampsia , Pregnant Women , Urine Specimen Collection , Weights and MeasuresABSTRACT
No abstract available.
Subject(s)
Female , Humans , Estrogen Replacement Therapy , Estrogens , Lipid MetabolismABSTRACT
No abstract available.