Lijian Yu

Effects of maternal oral administration of monosodium glutamate at a late stage of pregnancy on developing mouse fetal brain.

Monosodium glutamate (MSG) was shown to penetrate placental barrier and to distribute to embryonic tissues using [3H]glutamic acid ([3H]Glu) as a tracer. However, the distribution is not even; the uptake of MSG in the fetal brain was twice as great as that in the maternal brain in Kunming mice. Other maternal mice were given per os MSG (2.5 mg/g or 4.0 mg/g body weight) at 17-21 days of pregnancy, and their offspring behaviors studied. The results showed that maternal oral administration of MSG at a late stage of pregnancy decreased the threshold of convulsion in the litters at 10 days of age. Y-maze discrimination learning was significantly impaired in the 60-day-old filial mice. On the other hand, no significant difference in spatial learning or tail flick latency was measured between the experimental animals and the controls. The filial mice of MSG-treated mothers could either not grasp a rope tightly, or grasped the rope tightly but could not crawl along the rope at the beginning of the training. However, such mice, after training, could grasp and crawl along the rope as well as controls. Obvious neuronal damage was not detected in the periventricular organs or the hypothalamus under a light microscope. The rate of weight gain for experimental animals was greater than for controls throughout the period from 20 to 90 days. Mating of treated males with treated females resulted in pregnancies and normal offspring, indicating that oral administration of MSG at a late stage of pregnancy did not affected the reproductive capacity of the offspring. The possible differences and relationship between MSG-induced damage to developing human and rodent brain are discussed.

Potent protection of ferulic acid against excitotoxic effects of maternal intragastric administration of monosodium glutamate at a late stage of pregnancy on developing mouse fetal brain.

The present study was conducted to investigate a possible protection of ferulic acid against excitotoxic effects of maternal intragastric (ig) administration of monosodium glutamate (MSG) at a late stage of pregnancy on developing mouse fetal brain. [(3)H]-labeled glutamate was used as radiotracer to study the effect of ferulic acid on distribution of MSG in mouse fetal brain. MSG dissolved in distilled water (2.0 g/kg body weight, 640 kBq of [(3)H]glutamate/mouse, ig) or/and sodium ferulate (SF) (20, 40, 80 mg/kg body weight, ip), was given to pregnant mice at 17-19 days; the distribution of [(3)H] glutamate in the mouse fetal brains was measured at 30, 60, 90, 120 min after administration of MSG or/and SF. Maternal mice were given MSG (1.0, 2.0, 4.0 g/kg body weight, ig) or/and SF (20, 40, 80 mg/kg body weight, ip) simultaneously at 17-19 days of pregnancy, and then behavioral tests and histopathological observations were used to analyze glutamate-induced functional and morphological changes of the brains of their offspring, and Western blot analysis was performed for examining expressions of bcl-2 and caspase-3. The results showed that SF obviously inhibited the uptake of labeled glutamate in fetal brain. In addition, SF countered the effects of MSG on behavior, histopathology, genetic toxicity, and expression of apoptosis-related gene. The results suggest that ferulic acid is a novel competitive N-methyl-D-aspartate (NMDA) receptor antagonist and neuroprotector. In conclusion, maternal administration of ferulic acid has potent protective effects against glutamate-induced neurotoxicity in their filial mice.

Repair of Excitotoxic Neuronal Damage Mediated by Neural Stem Cell Lysates in Adult Mice

The present study aimed to investigate a possibility of brain repair from diseased or damaged disorders mediated by cell-free filtrate of neural stem cell (NSC) lysates (FNSCL). Mouse NSCs were isolated from the brains of embryos at 15 day postcoitum (dpc). The expression of the Nestin was examined by immunocytochemical technique. Sonication of NSCs cultured and nestin-positive was performed in a bath-type sonicator, and the cell-free filtrate was recovered from a filtrative step of the lysates. The animals in the monosodium glutamate MSG group received intragastric(ig) administration of MSG (2.0 g/kg per day) for 10 days the animals in the MSG+NSCs and MSG+FNSCL groups received intracerebroventricular transplantation of 10 ?l of NSC suspension, approximately 1.0×105 cells, or intracerebroventricular injection of 10 ?l of cell-free filtrate of lysates of approximately 1.0×105 NSCs on day 1 and day 11 after 10-d MSG exposure, respectively. The mice in control and MSG group were intracerebroventricularly administered with 10 ?l of DMEM instead of NSCs or FNSCL. On 11 day after intracerebroventricular transplantation of NSCs or intracerebroventricular injection of FNSCL, the test of Y-maze discrimination learning were performed, and then the histopathology of the animal brains was studied, to analyze MSG-induced functional and morphological changes and the effects of intracerebroventricular transplantation of NSCs or intracerebroventricular injection of FNSCL on the brain repair from MSG-induced excitotoxic injury. Both intracerebroventricular transplantation of NSCs and intracerebroventricular injection of FNSCL facilitated the brain repair following glutamate-induced excitotoxic injury in adult mice, suggesting that there are certain NSC factors inside NSCs which are effective in repairing glutamate-induced excitotoxic brain injury. Administration of FNSCL might be a cell-free-based therapeutic strategy to repair diseased or damaged central nervous system CNS tissue.

Antitumor and Antitumor-Promoting Actions of Macrophages and Their Relationship with Estrogen

Silica provides, in fact, a remarkable example of selective toxicity for macrophage by a substance of simple chemical composition and low chemical reactivity. Intraperitoneal injection of silica resulted in an increase of growth rate of subcutaneously implanted mouse sarcoma 180 (S180) in female BALB/c mice and of tumor incidence of two-stage mouse skin carcinogenesis in female ICR mice, but did not show any significant effects on tumor growth and carcinogenesis in male mice. In contrast, local administration of homologous macrophages led to the decrease of growth rate of subcutaneously implanted mouse S180 in female BALB/c mice and of tumor incidence of two-stage mouse skin carcinogenesis in female ICR mice. On the other hand, estradiol, estradiol plus macrophages or a large number of macrophages alone inhibited the tumor growth in male mice. It should be noted that estradiol plus macrophages had the most potent antitumor action among them. These results suggest that macrophages, especially estrogen-activated macrophages, may play an important role in antitumor and antitumor-promoting actions of organisms.

Repair of glutamate-induced excitotoxic neuronal damage mediated by intracerebroventricular transplantation of neural stem cells in adult mice.

To investigate a possibility of repairing damaged brain by intracerebroventricular transplantation of neural stem cells (NSCs) in the adult mice subjected to glutamate-induced excitotoxic injury. Mouse NSCs were isolated from the brains of embryos at 15-day postcoitum (dpc). The expression of nestin, a special antigen for NSC, was detected by immunocytochemistry. Immunofluorescence staining was carried out to observe the survival and location of transplanted NSCs. The animals in the MSG+NSCs group received intracerebroventricular transplantation of NSCs (approximately 1.0×105 cells) separately on day 1 and day 10 after 10-d MSG exposure (4.0 g/kg per day). The mice in control and MSG groups received intracerebroventricular injection of Dulbecco’s minimum essential medium (DMEM) instead of NSCs. On day 11 after the last NSC transplantation, the test of Y-maze discrimination learning was performed, and then the histopathology of the animal brains was studied to analyze the MSG-induced functional and morphological changes of brain and the effects of intracerebroventricular transplantation of NSCs on the brain repair. The isolated cells were Nestin-positive. The grafted NSCs in the host brain were region-specifically survived at 10-d post-transplantation. Intracerebroventricular transplantation of NSCs obviously facilitated the brain recovery from glutamate-induced behavioral disturbances and histopathological impairs in adult mice. Intracerebroventricular transplantation of NSCs may be feasible in repairing diseased or damaged brain tissue. 探讨脑室内神经干细胞移植修复成年小鼠谷氨酸神经毒性损伤的可能性。 从15日小鼠胚胎脑组织分离神经干细胞?采用免疫细胞化学技术检测细胞 Nestin 抗原表达; 通过免疫荧光染色观察所移植神经干细胞在体内的存活及定位。 除对照组外, 所有小鼠均以谷氨酸单钠(每天4.0 g/kg)灌胃, 连续10 天。 灌胃后第 1 天和 10 天, 谷氨酸加神经干细胞移植组行神经干细胞脑室内移植(1 × 105 细胞/鼠), 对照组和谷氨酸组注射 DMEM 液。 末次移植后第 11 天进行 Y 迷宫试验, 试验结束后进行小鼠脑病理检查, 以分析谷氨酸引起的脑功能和形态学上的改变。 所分离细胞呈 Nestin 阳性表达; 移植 10 天后所移植神经干细胞在小鼠脑中呈区域特异性存活; 脑室内移植神经干细胞能明显促进成年小鼠脑谷氨酸兴奋性毒性损伤的修复。 脑室内移植神经干细胞可用于疾病或损伤脑组织的修复。

Repair of glutamate-induced excitotoxic neuronal damage mediated by intracerebroventricular transplantation of neural stem cells in adult mice@@@脑室内神经干细胞移植修复谷氨酸导致的成年小鼠神经损伤

To investigate a possibility of repairing damaged brain by intracerebroventricular transplantation of neural stem cells (NSCs) in the adult mice subjected to glutamate-induced excitotoxic injury. Mouse NSCs were isolated from the brains of embryos at 15-day postcoitum (dpc). The expression of nestin, a special antigen for NSC, was detected by immunocytochemistry. Immunofluorescence staining was carried out to observe the survival and location of transplanted NSCs. The animals in the MSG+NSCs group received intracerebroventricular transplantation of NSCs (approximately 1.0×105 cells) separately on day 1 and day 10 after 10-d MSG exposure (4.0 g/kg per day). The mice in control and MSG groups received intracerebroventricular injection of Dulbecco’s minimum essential medium (DMEM) instead of NSCs. On day 11 after the last NSC transplantation, the test of Y-maze discrimination learning was performed, and then the histopathology of the animal brains was studied to analyze the MSG-induced functional and morphological changes of brain and the effects of intracerebroventricular transplantation of NSCs on the brain repair. The isolated cells were Nestin-positive. The grafted NSCs in the host brain were region-specifically survived at 10-d post-transplantation. Intracerebroventricular transplantation of NSCs obviously facilitated the brain recovery from glutamate-induced behavioral disturbances and histopathological impairs in adult mice. Intracerebroventricular transplantation of NSCs may be feasible in repairing diseased or damaged brain tissue. 探讨脑室内神经干细胞移植修复成年小鼠谷氨酸神经毒性损伤的可能性。 从15日小鼠胚胎脑组织分离神经干细胞?采用免疫细胞化学技术检测细胞 Nestin 抗原表达; 通过免疫荧光染色观察所移植神经干细胞在体内的存活及定位。 除对照组外, 所有小鼠均以谷氨酸单钠(每天4.0 g/kg)灌胃, 连续10 天。 灌胃后第 1 天和 10 天, 谷氨酸加神经干细胞移植组行神经干细胞脑室内移植(1 × 105 细胞/鼠), 对照组和谷氨酸组注射 DMEM 液。 末次移植后第 11 天进行 Y 迷宫试验, 试验结束后进行小鼠脑病理检查, 以分析谷氨酸引起的脑功能和形态学上的改变。 所分离细胞呈 Nestin 阳性表达; 移植 10 天后所移植神经干细胞在小鼠脑中呈区域特异性存活; 脑室内移植神经干细胞能明显促进成年小鼠脑谷氨酸兴奋性毒性损伤的修复。 脑室内移植神经干细胞可用于疾病或损伤脑组织的修复。