• Clinical and Experimental Pediatrics
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• v.57 no.6
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• pp.251-256
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• 2014

Severe intraventricular hemorrhaging (IVH) in premature infants and subsequent posthemorrhagic hydrocephalus (PHH) causes significant mortality and life-long neurological complications, including seizures, cerebral palsy, and developmental retardation. However, there are currently no effective therapies for neonatal IVH. The pathogenesis of PHH has been mainly explained by inflammation within the subarachnoid spaces due to the hemolysis of extravasated blood after IVH. Obliterative arachnoiditis, induced by inflammatory responses, impairs cerebrospinal fluid (CSF) resorption and subsequently leads to the development of PHH with ensuing brain damage. Increasing evidence has demonstrated potent immunomodulating abilities of mesenchymal stem cells (MSCs) in various brain injury models. Recent reports of MSC transplantation in an IVH model of newborn rats demonstrated that intraventricular transplantation of MSCs downregulated the inflammatory cytokines in CSF and attenuated progressive PHH. In addition, MSC transplantation mitigated the brain damages that ensue after IVH and PHH, including reactive gliosis, cell death, delayed myelination, and impaired behavioral functions. These findings suggest that MSCs are promising therapeutic agents for neuroprotection in preterm infants with severe IVH.

• The Korean Journal of Physiology and Pharmacology
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• v.11 no.3
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• pp.89-95
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• 2007

Polygala tenuifolia (PT) is one of the most well-known traditional herbal medicines in Korea which is commonly used for the treatment of cardiovascular symptoms. The anti-ischemic effects of PT in isolated rat heart was investigated by analyzing changes in blood pressure, aortic flow, coronary flow, and cardiac output. And, its underlying mechanism was examined by quantitating intracellular calcium content in rat neonatal cardiomyocytes. Rats were divided into two groups: an ischemia-induced group without any treatment, and an ischemia-induced group treated with PT. Ischemia of isolated heart was induced by stopping the supply of oxygen and buffer for 10 min. The isolated heart was exposed to PT for the first 5 min of 10 min ischemia. PT treatment significantly prevented the decreases of perfusion pressure, aortic flow, coronary flow, and cardiac output under ischemic conditions. In addition, hemodynamics (except heart rate) of the PT-treated group was significantly recovered 60 min after reperfusion compared to the control group (systolic aortic pressure: 83.3% vs. 64.9%, aortic flow volume: 69.5% vs. 48.7%, coronary flow volume: 77.7% vs. 58.4%, and cardiac output: 71.6% vs. 51.2%, p < 0.01). As for the underlying mechanism, PT significantly prevented intracellular calcium increase which was induced by isoproterenol (p < 0.01), suggesting that the anti-ischemic effect of PT is mediated by inhibition of intracellular calcium increase.

• Animal cells and systems
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• v.4 no.4
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• pp.367-373
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• 2000

In the present study we determined if NELL2, a neural tissue-specific protein containing 6 epidermal growth factor (EGF)-like repeat domains, plays an important role in the regulation of puberty initiation in the rat hypothalamus. We origin811y found that NELL2 is a new estrogen-responsive gene in hypothalami derived from estrogen-sterilized and control rats using a PCR differential display. In the 40-day-old female rat hypothalamus, NELL2 was up-regulated by neonatal estrogen treatment. In situ hybridization histochemistry showed that NELL2 is very abundant in the ventromedial hypothalamic nucleus that is responsible for the control of sex behavior. NELL2 mRNA level in the medial basal hypothalamus showed a dramatic increase before female puberty onset, which suggests that NELL2 may be involved in the process regulating female puberty onset. We attemped to block NELL2 synthesis with intracerebroventricular injection of an antisense oligodeoxynucleotide (ODN) to the NELL2 mRNA, and examined its effect on the puberty onset of the female rat. The antisense ODN significantly delayed puberty initiation determined by vaginal opening. In summary, NELL2 may play an important role in the regulation of female puberty onset.

• Neonatal Medicine
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• v.17 no.2
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• pp.181-192
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• 2010

Purpose: Current studies have demonstrated the neuroprotective effects of dizocilpine (MK-801) in many animal models of brain injury, including hypoxic-ischemic (HI) encephlopathy, trauma and excitotoxicity, but limited data are available for those during the neonatal periods. Here we investigated whether dizocilpine can protect the developing rat brain from HI injury via anti-apoptosis. Methods: In an in vitro model, embryonic cortical neuronal cell culture of Sprague-Dawley (SD) rats at 18-day gestation was done. The cultured cells were divided into three groups: normoxia (N), hypoxia (H), and hypoxia treated with dizocilpine (HD). The N group was prepared in 5% $CO_2$ incubators and the other groups were placed in 1% $O_2$ incubators (94% N2, 5% $CO_2$) for 16 hours. In an in vivo model, left carotid artery ligation was done in 7-day-old SD rat pups. The animals were divided into six groups; hypoxia (N), hypoxia (H), hypoxia with sham-operation (HS), hypoxia with operation (HO), HO treated with vehicle (HV), and HO treated with dizocilpine (HD). Hypoxia was made by exposure to a 2 hour period of hypoxic incubator (92% N2, 8% $O_2$). Results: In the in vitvo and in vivo models, the expressions of Bcl-2 in the hypoxia groups were reduced compared to the normoxia group. whereas those in the dizocilpine-treated group were increased compared to the hypoxia group. However. the expressions of Bax and caspase-3 and the ratio of Bax/Bcl-2 were revealed reversely. Conclusion: Dizocilpine has neuroprotective property over perinatal HI brain injury via anti-apoptosis.

• Neonatal Medicine
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• v.18 no.1
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• pp.59-69
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• 2011

Purpose: Current studies have demonstrated the neuroprotective effects of 6-cyano-7-nitroquinoxalin-2,3-dione (CNQX) in many animal models of brain injury, including hypoxic-ischemic (HI) encephlopathy, trauma and excitotoxicity, but limited data are available for those during the neonatal periods. Here we investigated whether CNQX can protect the developing rat brain from HI injury via mediation of nitric oxide synthase. Methods: In an in vivo model, left carotid artery ligation was done in 7-day-old Sprague-Dawley (SD) rat pups. The animals were divided into six groups; normoxia (N), hypoxia (H), hypoxia with sham-operation (HS), hypoxia with operation (HO), HO treated with vehicle (HV), and HO treated with CNQX at a dose of 10 mg/kg (HC). Hypoxia was made by exposure to a 2 hr period in the hypoxic chamber (92% $N_2$, 8% $O_2$). In an in vitro model, embryonic cortical neuronal cell culture of SD rats at 18-day gestation was done. The cultured cells were divided into three groups: normoxia (N), hypoxia (H), and hypoxia treated with CNQX (HC). The N group was prepared in 5% $CO_2$ incubators and the other groups were placed in 1% $O_2$) incubators (94% $N_2$, 5% $CO_2$) for 16 hr. Results: In the in vitvo and in vivo models, the expressions of iNOS and eNOS were reduced in the hypoxia group when compared to the normoxia group, whereas they were increased in the CNQX-treated group compared to the hypoxia group. In contrast, the expression of nNOS was showed reversely. Conclusion: CNQX has neuroprotective property over perinatal HI brain injury via mediation of nitric oxide synthase.

• Clinical and Experimental Pediatrics
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• v.46 no.8
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• pp.789-794
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• 2003

Purpose : We intended to evaluate the effect of hypoxia-ischemia on extracellular striatal monoamine metabolism in neonatal rat brains by in vivo microdialysis. Methods : The right common carotid arteries of five or six-day old rats were surgically ligated, and the probes for microdialysis were inserted into the right striatum with stereotaxic instrument. After stabilization for two hours, artificial cerebrospinal fluid was infused via the probe for microdialysis and samples were collected during hypoxia-ischemia and recovery periods at 20 minute intervals. The concentrations of DA(dopamine), DOPAC(3,4-di-hydroxyphenyl acetic acid), HVA(homovanillic acid), NE(norepinephrine), and 5-HIAA(5-hydroxy indole-acetic acid) were measured by HPLC(high performance liquid chromatography) and the changes were analysed. Results : The striatal levels of dopamine metabolites such as DOPAC and HVA, were significantly decreased during hypoxia-ischemia, and increased to their basal level during reoxygenation(P<0.05). Dopamine mostly increased during hypoxia but statistically not significant(P>0.05). DOPAC showed the most remarkable decrease($23.0{\pm}4.2%$, P<0.05), during hypoxia-ischemia and increase to the basal levels during reoxygenation($120.8{\pm}54.9%$, P<0.05), and HVA showed the same pattern of changes as those of DOPAC during hypoxia-ischemia($35.3{\pm}7.6%$ of basal level, P<0.05) and reoxygenation ($105.8{\pm}32.3%$). However, the level of NE did not show significant changes during hypoxia-ischemia and reoxygenation. The levels of 5-HIAA decreased($74.9{\pm}3.1%$) and increased($118.1{\pm}7.8%$) during hypoxia-ischemia and reoxygenation, respectively(P<0.005). Conclusion : Hypoxia-ischemia had a significant influence on the metabolism of striatal monoamine in neonatal rat brains. These findings suggest that monoamine, especially dopamine, and its metabolites could have a significant role in the pathogenesis of hypoxic-ischemic injury of neonatal rat brains.

• Journal of Society of Preventive Korean Medicine
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• v.10 no.2
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• pp.31-49
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• 2006

This study was undertaken to investigate the effects of Gyoaesamultang in pregnant rats and their fetuses. Female Sprague-Dawley rats were orally administered with the Gyoaesamultang at dose of 5mg/kg/day for 20 days. Pregnant rats were sacrificed at 20th day of gestation, and observed internal and reproductive organs. Approximately, live fetuses in the 20th day of gestation were randomly selected and fixed in 95% ethanol. To observe skeletal malformations, fetuses were stained with alcian blue and alizarin red S. Maternal body weight of Gyoaesamultang treated group has a tendency to increase compared to that of control group. There were no significant difference in internal and reproductive organs. There were no significant changes between two groups in blood chemistry and hematological values. There were no significant changes in number of corpus luteum, implantation, live fetuses and implantation rate, delivery rate, late resorption rate and sex ratio. But Gyoaesamultang administered group showed lower early resorption rate than the control group. Neonatal body weight and number of fetus of Gyoaesamultang group were increased to that of control group. The fetuses of dams treated with Gyoaesamultang didn't showed external malformation. Vertebral and sternal variations were observed in Gyoaesamultang group but, compared to the control, those variations were insignificant. The number of ribs, cervical, thoracic, and lumber were normal. The number of sacral and caudal vertebrae were increased. Fetuses treated with Gyoaesamultang showed significant difference in the number of caudal vertebra(P<0.01). From these results, it can be concluded that Gyoaesamultang showed no toxicity effects on maternal body weight, early resorption rate, and number of live fetuses. There were no significant changes in organ weight, hematological data, reproductive organs. Although skeletal variations were showed in vertebrate and sternum, Gyoaesamultang were shown insignificant changes in bone malformation.

• Journal of Society of Preventive Korean Medicine
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• v.14 no.2
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• pp.91-104
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• 2010

The experiments were undertaken to evaluate the effects of herbal medicine, Bojungiggitang and Gwibitang in pregnant rats and their fetuses. Female Sprague-Dawley rats were orally administered with the Bojungiggitang and Gwibitang at dose of 5ml/kg/day for 20 days. Pregnant rats were sacrificed at 20th day of gestation, and the internal and reproductive organs. Approximately live fetuses in the 20th day of gestation were randomly selected and fixed in 95% ethanol. To observe skeletal malformations, fetuses were stained with alcian blue and alizarin red S. Maternal body weights of Bojungiggitang and Gwibitang treated group has a tendency to increase compared to that of control group. There were no significant differences in internal and reproductive organs. There were no significant changes between two groups in blood chemistry and hematological values. There were no significant changes in number of corpus luteum, implantation and live fetuses. But Bojungiggitang and Gwibitang administered group showed higher implantation rate than the control group. Also, Bojungiggitang and Gwibitang administered groups showed lower early resorption rate than the control group. And Gwibitang had the higher value in all the other groups in all items. From the sex ratio, the number of females were larger than the number of males in the control group, and more males than females in Gwibitang administered group. Neonatal body weight and the number of fetus of Bojungiggitang and Gwibitang group were higher than that of control group. The fetuses of dams treated with Bojungiggitang and Gwibitang did not show external malformation. Vertebral and sternal variations were observed in Bojungiggitang and Gwibitang administered group compared to the control group. Those variations were insignificant. There were no significant changes in number of ribs, cervical, thoracic, lumbar, sacral and caudal vertebras. From these results, it can be concluded that Bojungiggitang and Gwibitang showed no toxic effects on maternal body weight and the number of live fetuses. There were no significant changes in organ weight, hematological data, and reproductive organs. Although skeletal variations were shown in vertebra and sternum, Bojungiggitang, Gwibitang were shown insignificant changes in bone malformation.

• Applied Microscopy
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• v.23 no.1
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• pp.56-76
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• 1993

To investigate the histogenesis of tracheal epithelium in Sprague-Dawley strain rat, the author has used the fetal rats at the 16th, 18th, 20th and 22nd prenatal day and neonatal rats at the 1st and 7th day as well as rats at age of 5, 10 and 15 weeks after birth as experimental animals. Specimens were double stained with uranyl acetate and lead citrate for electron microscopic study. The results obtained were as follows; 1. At the 16th day of gestational age, ciliated cells were found in tracheal epithelium and light and dark ciliated cells possessing numerous mitochondria and smooth endoplasmic reticulum in the cytoplasm at the 22nd day of gestational age of the rat are observed. 2. At the 16th day of gestataional age, basal cells lying upon the basement membrane and having large numbers of glycogen particles in the cytoplasm, were found and at the 22nd day of gestational age, basal cells possessing numerous polysomes in the cytoplasm were observed. 3. At the 20th gestational age of the rat, microvillous cells possessing many rough endoplasmic reticulum and mitochondria as well as microvilli protruding into the lumen were found in tracheal epithelium. 4. At the 5th week after birth brush cell having profound filamentous strands and many pinocytic vesicles in the cytoplasm, was visible in the tracheal epithelium. 5. At the 15th week after birth large proportions of tracheal epithelium were lined with ciliated cells. Cosequently it is suggested that pseudostratified ciliated columnar epithelium was differentiated at the 16th day of gestational age, in addition cytoplasmic organelles of the microvillous and basal cells were matured at the 20th and 22nd gestational age, respectively and most of the part of the tracheal epithelium was lined with ciliated cells at the 15th week after birth.

• Journal of Environmental Health Sciences
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• v.32 no.4 s.91
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• pp.342-352
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• 2006

The experiments was undertaken to evaluate the effects of herbal medicine, Dalsaengtang, in pregnant rats and fetuses. Female Sprague-Dawley rats were orally administered with the Dalsaengtang at dose of 5 mg/kg/day for 20 days. Pregnant rats were sacrificed at 20th day of gestation, and observed internal and reproductive organs. Approximately live fetuses in the 20th day of gestation were randomly selected and fixed in 95% ethanol. To observe skeletal malformations, fetuses were stained with alcian blue and alizarin red S. Maternal body weight of dalsaengtang treated group has a tendency to increase compared to that of control group. The relative liver and kidney weights of dalsaengtang treated group were also increased to that of control group. There were no significant changes between two groups in blood chemistry and hematological values. There were no significant changes in number of corpus luteum, implantation, live fetuses and implantation rate, delivery rate, late resorption rate and sex ratio. But Dalsaengtang administered group showed lower early resorption rate than the control group. From the sex ratio, number of females, bigger than number of males in the control group, and more males than females in Dalsaengtang administered group. Neonatal body weight and number of fetus of Dalsaengtang group were increased to that of control group. The fetuses of dams treated with Dalsaengtang didn't showed external malformation. Vertebral and sternal variations were observed in Dalsaengtang group but, compared to the control, those variations were insignificant. The number of ribs, cervical, thoracic, and lumber were normal. The number of sacral and caudal vertebrae were increased. Fetuses showed significant difference in the number of caudal vertebra (P<0.01). From these results, it can be concluded that Dalsaengtang showed no toxicity effects on maternal body weight, early resorption rate, and number of live fetuses. There were no significant changes in organ weight, hematological data, reproductive organs. Although skeletal variations were showed in vertebrate and sternum, Dalsaengtang did not shown significant changes in bone malformation.