• Clinical and Experimental Pediatrics
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• 제57권6호
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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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• 제11권3호
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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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• 제4권4호
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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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• 제17권2호
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• pp.181-192
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• 2010

목적: 비경쟁적 NMDA 길항제인 dizocilpine (MK-801)는 저산소성 허혈성 뇌병증, 외상성 뇌손상, 흥분독성과 같은 신경 질환의 동물 모델에서 보호 효과가 있다고 발표되고 있지만 주산기 가사로 인한 저산소성 허혈성 뇌병증의 치료제로서 그 기전이 명확하게 밝혀지지 않았다. 저자들은 dizocilpine을 이용하여 주산기 저산소성 허혈성 뇌병증의 치료제로서 항 세포사멸사을 통한 기전을 알아보고자 하였다. 방법: 생체외 실험으로 재태기간 19일된 태아 흰쥐의 대뇌피질 세포를 배양하여 3군(정상산소군, 저산소군, 뇌손상 전dizocilpine 투여군)으로 나누었다. 정상산소군은 5% $CO_2$ 배양기(95% air, 5% $CO_2$)에 두었고, 저산소군과 뇌손상 전 dizocilpine 투여군($10{\mu}g/mL$)은 1% $O_2$ 배양기(94% $N_2$, 5% CO2)에서 16시간 동안 뇌세포손상을 유도하였다. 생체내 실험으로 저산소성 허혈성 뇌병증의 동물 모델에서는 생후 7일된 신생백서의 좌측 총 경동맥을 결찰한 후 6개 군(정상산소군, 수술 없이 저산소군, sham 수술 후 저산소군, 수술 후 저산소군, vehicle 투여후 저산소군, dizocilpine 투여 후 저산소군)으로 나누었고, 저산소 손상은 특별히 제작한 통속에서 2시간 동안 8% $O_2$에 노출시켰다. Dizocilpine은 뇌손상 전후 30분에 체중 kg당 10 mg를 투여하였고, 저산소 손상 후 7일째 조직을 실험하였다. 생체외 내 실험 모두 세포사멸사와 관련된 Bcl-2, Bax, caspase-3항체와 primer를 이용하여 western blots과 실시간 중합효소연쇄반응을 실시하였다. 결과: 세포사멸사와 관련된 생체외 내 실험에서 Bcl-2의 발현은 저산소군에서 정상산소군보다 감소하였으나 dizocilpine 투여군에서 저산소군보다 증가하였다. 그러나 Bax와 caspase-3 발현 및 Bax/Bcl-2의 비는 반대로 표현되었다. 결론: 본 연구에서 dizocilpine은 항 세포사멸사를 통하여 주산기 저산소성 허혈성 뇌손상에서 신경보호 역할을 하는 것을 알 수 있었다.

• Neonatal Medicine
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• 제18권1호
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• pp.59-69
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• 2011

목적: 6-cyano-7-nitroquinoxalin-2,3-dione (CNQX)는 저산소성허혈성뇌병증, 외상성뇌손상, 흥분독성과 같은 뇌 손상동물 모델에서 보호 효과가 있다고 발표되고 있지만 신생아기에 그 효과에 대해서는 아직 제한적이다. 저자들은 CNQX를 이용하여 저산소성허혈성뇌손상을 동반한 발달 과정에 있는 흰쥐 뇌에 산화질소합성효소 중재를 통한 뇌 보호 효과를 알아보고자 하였다. 방법: 생체내 실험으로 생후 7일된 신생 흰쥐의 좌측 총 경동맥을 결찰한 후 6개군(정상산소군, 수술없이 저산소군, sham수술 후 저산소군, 수술 후 저산소군, vehicle 투여 후 저산소군, CNQX 투여 후 저산소군)으로 나누었고, 저산소 손상은 특별히 제작한 통속에서 2시간 동안 8% $O_2$에 노출시켰다. CNQX은 뇌손상 전 30분에 체중 kg당 10 mg를 투여하였다. 생체외 실험으로 재태기간 18일된 태아 백서의 대뇌피질 세포를 배양하여 정상산소군은 5% $CO_2$ 배양기(95% air, 5% $CO_2$)에 두었고, 저산소군과 뇌손상 전 CNQX 투여군(10 ${\mu}g$/mL)은 1% $O_2$). 배양기(94% $N_2$, 5% $CO_2$)에서 16시간동안 뇌세포손상을 유도하였다. 생체내 외 실험 모두 산화질소합성효소와 관련된 iNOS, eNOS, nNOS 항체와 primer를 이용하여 western blotting과 실시간중합효소연쇄반응을 시행하였다. 결과: 산화질소합성효소와 관련된 생체외 내 실험에서 iNOS와 eNOS의 발현은 저산소군에서 정상산소군보다 감소하였으나 CNQX 투여군에서는 저산소군보다 증가하였다. nNOS의 발현은 반대로 표현되었다. 결론: 본 연구에서 CNQX는 산화질소합성효소 중재를 통하여 주산기 저산소성 허혈성 뇌손상에서 신경보호 역할을 하는 것을 알 수 있었다.

• Clinical and Experimental Pediatrics
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• 제46권8호
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• pp.789-794
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• 2003

목 적: 신생 흰쥐의 뇌에 저산소-허혈을 유발하여 선조체 monoamine과 그 대사물들의 변화를 관찰하여, 저산소-허혈 손상 시 dopamine과 monoamine의 역할을 관찰하고자 하였다. 방 법 : 생후 5-6일 된 신생 흰쥐의 우측 총경동맥을 결찰 후 우측 선조체에 microdialysis probe를 삽입하였다. 2시간 동안의 안정기를 거친 후, probe를 통해 기저치를 수집하고, 바로 8% 산소에 2시간 동안 노출시키고, 2시간 동안 회복시키며 20분 간격으로 수집한 샘플을 HPLC를 통해 분석하였다. 결 과 : 1) Dopamine은 저산소-허혈기에 급격히 증가하는 경향을 보였으나 통계적 유의성은 없었다(P>0.05). 2) DOPAC은 저산소-허혈 동안 기저치의 $23.0{\pm}4.2%$까지 감소하였다가, 재산소화 동안에 기저치의 $120.8{\pm}54.9%$까지 증가하였다(P<0.05). 3) HVA는 DOPAC과 같은 변화를 보였으나 덜 현저하였고, 저산소-허혈 동안 기저치의 $35.3{\pm}7.6%$까지 감소하였다가 재산소화 동안에 $105.8{\pm}32.3%$까지 회복되었다(P<0.05). 4) NE은 저산소-허혈 노출과 재산소화 동안 유의한 변화를 보이지 않았다(P>0.05). 5) 5-HIAA는 저산소-허혈 동안 서서히 감소하였다가 재산소화 동안 증가하였고, 그 변화는 통계적으로 유의하였다(P<0.05). 6) 실험 중 serotonin은 검출되지 않았다. 결 론: 저산소-허혈은 미성숙 신생 횐쥐의 뇌 선조체의 monoamine 대사에 영향을 끼쳤으며, 이 결과는 monoamine, 특히 dopamine과 그 대사물들이 신생 흰쥐 뇌의 저산소-허혈손상의 기전에 중요한 역할을 할 수 있다는 가능성을 제시한다.

• 대한예방한의학회지
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• 제10권2호
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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.

• 대한예방한의학회지
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• 제14권2호
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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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• 제23권1호
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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.

• 한국환경보건학회지
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• 제32권4호
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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.