• Journal of Food Hygiene and Safety
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• v.6 no.1
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• pp.13-26
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• 1991

This study was performed for searching for non-hepatectomy medium-term bioassay model by using newborn female rats. Newborn female Sprague-Dawley rats (1 day old) were given an intraperitoneal injection of 150 mg/kg of diethylnitrosamine (DENA). After three weeks, all rats were weaned and divided into three groups. Group 1 were fed on diets containing 0.01% 2-acetylaminofluorene (2-AAF) as a promoter for three weeks. Group 2 were given 0.05% phenobarbital (PB) in drinking water as a promoter for 8 weeks. Group 3 was control group. The autopsy was carried out at 4 weeks and 8 weeks after weaning. Preneoplastic lesions were indentified with immunohistochemical staining for glutathione S-transferase placental form (GST-P). In liver weight to body weight ratios, group 2 showed significant difference from group 1 (p<0.001) at 4 weeks after weaning. Group 1 and group 2 showed significant difference from group 3 at 8 weeks after weaning (p<0.0I, p<0.001), respectively. In quantitative analysis for GST-P positive lesion area by using Image Analyzer, group 1 and group 2 represented significant difference in comparison with group 3 at early 4 weeks after weaning (p

• Korean Journal of Bronchoesophagology
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• v.5 no.1
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• pp.42-48
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• 1999

Background： This study was undertaken to detect the patterns of ciliogenesis in newborn rats trachea. Materials and Methods： The experimental animals(Sprague-Dawley strain) were divided five groups, one day, two day, three day, five day and seven day newborns as experimental groups. To obtain differential distribution of $\alpha$-tubulins in the ciliated cells and patterns of ciliogenesis, we used immunohistochemical stain method with mouse anti $\alpha$-tubulin monoclonal antibody as the primary antibody and gold particles conjugated goat anti mouse IgG as the secondary antibody. And we observed the specimens by electron microscope (Hitach-600 Model). Results : 1) The distribution of the $\alpha$ -tubulin reactions in apical zone was slightly decreased from three day after birth. 2) From 5th day after birth, the decreasing number of gold particles in intermediate zone was remarkable. 3) On the comparison with the other zones, the number of gold particles in the Golgi zone for seven days showed no statistical difference. Conclusion : The ciliogenesis of the tracheal ciliated cells in early newborn rat were made via centriolar and acentriolar pathways, in late groups, from five day after birth, the major ciliogenesis pattern might be centriolar pathway.

• Clinical and Experimental Pediatrics
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• v.64 no.1
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• pp.37-43
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• 2021

Background: Animal studies have shown that a leukocyte influx precedes the development of bronchopulmonary dysplasia (BPD) in premature sheep. The CXC chemokine receptor 2 (CXCR2) pathway has been implicated in the pathogenesis of BPD because of the predominance of CXCR2 ligands in tracheal aspirates of preterm infants who later developed BPD. Purpose: To test the effect of CXCR2 antagonist on postnatal systemic and pulmonary inflammation and alveolarization in a newborn Sprague-Dawley rat model of BPD. Methods: Lipopolysaccharide (LPS) was injected intraperitoneally (i.p.) into the newborn rats on postnatal day 1 (P1), P3, and P5 to induce systemic inflammation and inhibit alveolarization. In the same time with LPS administration, CXCR2 antagonist (SB-265610) or vehicle was injected i.p. to investigate whether CXCR2 antagonist can alleviate the detrimental effect of LPS on alveolarization by attenuating inflammation. On P7 and P14, bronchoalveolar lavage fluid (BALF) and peripheral blood (PB) were collected from the pups. To assess alveolarization, mean cord length and alveolar surface area were measured on 4 random nonoverlapping fields per animal in 2 distal lung sections at ×100 magnification. Results: Early postnatal LPS administration significantly increased neutrophil counts in BALF and PB and inhibited alveolarization, which was indicated by a greater mean cord length and lesser alveolar surface area. CXCR2 antagonist significantly attenuated the increase of neutrophil counts in BALF and PB and restored alveolarization as indicated by a decreased mean cord length and increased alveolar surface area in rat pups exposed to early postnatal systemic LPS. Conclusion: CXCR2 antagonist preserved alveolarization by alleviating pulmonary and systemic inflammation induced by early postnatal systemic LPS administration. These results suggest that CXCR2 antagonist can be considered a potential therapeutic agent for BPD that results from disrupted alveolarization induced by inflammation.

• Neonatal Medicine
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• v.17 no.1
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• pp.44-52
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• 2010

Purpose : The aim of this study was to develop a model for necrotizing enterocolitis (NEC) in the neonatal rat using endotoxin and hypoxia, a plausible insult in a neonatal intensive care and to investigate the role of apoptosis as the underlying mechanism. Methods : Newborn rats were given oral endotoxin and intermittent 8% hypoxia$\pm$caspase inhibitor. The intestinal histology was evaluated using hematoxylin-eosin staining. Apoptosis was analyzed with TUNEL staining and by measuring the caspase 3 activity in the intestinal lysates. IEC-6 cells were assessed for apoptosis and the expression of Bax, Bcl-2, Fas and FasL was measured after treatment with endotoxin and hypoxia. Results : Oral endotoxin (5 mg/kg) and exposure to 8% hypoxia of 60-min duration twice induced human NEC-like lesions in the rat intestine. Intestinal tissue revealed increased apoptosis and caspase-3 activity. After caspase inhibitor treatment, the grades of both apoptosis and NEC were significantly reduced. IEC-6 cells exhibited increased apoptosis and caspase 3 activity after endotoxin and hypoxia treatment and significantly increased Bax/Bcl- 2 ratio compared to control cells. Conclusion : This neonatal rat model of NEC which was induced by oral endotoxin and intermittent hypoxia showed increased apoptosis of intestinal epithelial cells that was mediated by caspase 3 activation. Our model has a advantage in the study of NEC because the use of much more clinically plausible insults may provide a suitable model for the investigation of its pathophysiology and therapeutic trials.

• Physical Therapy Korea
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• v.16 no.2
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• pp.50-58
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• 2009

The purpose of this study was to test that motor skill training enhance motor function and cerebellar development. Using an animal model of fetal alcohol syndrome-which equates peak blood alcohol concentrations across developmental period-critifical periods for the effect of alcohol on body and cerebellar weigh was examined. The effect of motor skill training on motor function and cerebellar development of rat exposed alcohol on postnatal days 4 through 10 were studied. Newborn rats were assigned to one of two groups: (1) Control group (CG), via artificial rearing to milk formula and (2) experimental groups (EG), via 4.5g/kg/day of ethanol in a milk solution. After completion of the treatments, the pups were fostered back to lactating dams, and wearing they were raised in standard caged until they were postnatal 48 days. Rats from experimental group of postnatal treatment then spent 10 days in one of two groups: Experimental group II (EGII) was had got motor skill training (training traverse a set of 6 elevated obstacles) for 4 weeks. Experimental group I (EGI) was not trained. Before sacrificing, the rat got examined two behavioral test, body weigh and cerebellar weigh, then coronal sections were processed. The section was investigated the Purkije cell in the cerebellum using light microscope. The results of this study were as follows. 1. In body weight test, the outcome of alcohol groups were significantly lower than the normal group. 2. In cerebellar weight test, the outcome of EGI were significantly lower than CG and EGII. 3. In motor behavioral test, the outcome of EGI was significantly lower than NG and EGII. 4. In Purkinje cells counting test, the outcome of EGI was significantly lower than the NG and EGII. These result suggest that improved motor function induced by motor skill training after postnatal exposure is associated with dynamically altered expression of Purkinje cells and that is related with cerebellar function. Also, these data can potentially serve as a model for therapeutic intervention.

• Clinical and Experimental Pediatrics
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• v.51 no.8
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• pp.874-878
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• 2008

Purpose : This study was undertaken to develop an animal model of periventricular leukomalacia (PVL) induced by in utero clamping of pregnant rat aorta in fetal rats. Methods : A timed pregnanct Sprague-Dawley rat on embryonic day 21 just prior to delivery was sedated and anesthetized, and a Harvard ventilator for small animals was applied. Following laparotomy, the maternal aorta was clamped reversibly for 40 minutes using a surgical clip. The fetal rats were then delivered by Cesarean section, resuscitated if necessary, and reared by a surrogate mother rat until postnatal day 21 to obtain the brain specimen. After systemic perfusion and fixation, $10{\mu}m$ thick serial brain sections were obtained and stained for pathologic examination and assessment of ventriculomegaly. Ventriculomegaly was assessed by the measured ventricle to total brain volume ratio. Results : Eight out of eleven fetal rats (73%) survived in the ischemia group after induction of in utero ischemia by clamping maternal rat aorta, and all ten survived in the control group. Body and brain weights measured at postnatal day 21 were significantly lower in the ischemia group compared to the control group. In pathologic findings, significant ventriculomagaly ($3.67{\pm}1.21%$ vs. $0.23{\pm}0.06%$) was observed in the ischemia group compared to the control group; although cystic lesion was not observed, mild (n=6) and moderate (n=2) rerefaction of the brain tissue was observed. Conclusion : A fetal rat model of PVL induced by in utero clamping of pregnant rat aorta was developed.

• Korean Journal of Agricultural Science
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• v.43 no.1
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• pp.72-79
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• 2016

It has long been known that nutritional and environmental influences during the early developmental period affect the biological mechanisms which determine animal metabolism. This phenomenon, termed 'metabolic imprinting', can cause subtle but long-lasting responses to prenatal and postnatal nutrition and even be passed onto the next generation. A large amount of research data shows that nutrient availability, in terms of quantity as well as quality, during the early developing stages can decrease the number of newborn piglets and their body weight and increase their susceptibility to death before weaning. However, investigation of potential mechanisms of 'the metabolic imprinting' effect have been scant. Therefore, it remains unknown which factors are responsible for embryonic and early postnatal nutrition and which factors are major determinants of body weight and number of new born piglets. Intrauterine undernutrition, for example, was studied using a rat model providing dams 50% restricted nutrients during pregnancy and the results showed significant decreases in birth weight of newborns. This response may be a characteristic of a subset of modulations in embryonic development which is caused by the metabolic imprinting. Underlying mechanisms of intrauterine undernutrition and growth retardation can be explained in part by epigenetics. Epigenetics modulate animal phenotypes without changes in DNA sequences. Epigenetic modifications include DNA methylation, chromatin modification and small non-coding RNA-associated gene silencing. Precise mechanisms must be identified at the morphologic, cellular, and molecular levels by using interdisciplinary nutrigenomics approaches to increase pig production. Experimental approaches for explaining these potential mechanisms will be discussed in this review.

• Physical Therapy Korea
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• v.12 no.3
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• pp.56-66
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• 2005

The purposes of this study were to test that complex motor training enhance motor function significantly, to test change in cerebellum, and to test the synaptic plasticity into the immunohistochemistry response of synaptophysin. Using an animal model of fetal alcohol syndrome - which equates peak blood alcohol concentrations across developmental period - the effects of alcohol on body weight during periods were examined. The effect of complex motor training on motor function and synaptic plasticity of rat exposed alcohol on postnatal days 4 through 10 were studied. Newborn rats were assigned to one of two groups: (1) normal group (NG), via artificial rearing to milk formula and (2) alcohol groups (AG), via 4.5 g/kg/day of ethanol in a milk solution. After completion of the treatments, the pups were fostered back to lactating dams, where they were raised in standard cages (two-and three animals per cage) until they were postnatal 48 days. Rats from alcohol group of postnatal treatment then spent 10 days in one of two groups: Alcohol-experimental group was had got complex motor training (learning traverse a set of 6 elevated obstacles) for 4 weeks. The alcohol-control group was not trained. Before consider replacing with "the experiment/study", (avoid using "got" in writing) the rats were examined during four behavioral tests and their body weights were measured, then their coronal sections were processed in rabbit polyclonal antibody synaptophysin. The synaptophysin expression in the cerebellar cortex was investigated using a light microscope. The results of this study were as follows: 1. The alcohol groups contained significantly higher alcohol concentrations than the normal group. 2. The alcohol groups had significantly lower body weights than the normal group. 3. In alcohol groups performed significantly lower than the normal group on the motor behavioral test. 4. In alcohol-control group showed significantly decreased immunohistochemistric response of the synaptophysin in the cerebellar cortex compared to the nomal group. These results suggest that improved motor function induced by complex motor training after postnatal exposure is associated with dynamically altered expression of synaptophysin in cerebellar cortex and that is related with synaptic plasticity. Also, these data can potentially serve as a model for therapeutic intervention.

• Neonatal Medicine
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• v.15 no.1
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• pp.32-37
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• 2008

Purpose : Perinatal asphyxia is an important cause of neonatal mortality and subsequent lifelong neurodevelopmental handicaps. Although many treatment strategies have been tested, there is currently no clinically effective treatment to prevent or reduce the harmful effects of hypoxia and ischemia in humans. In the clinical setting, maternal hyperthermia induces adverse effects on the neonatal brain, but recent studies have shown that hyperthermic pretreatment (PT) plays some role in hypoxic-ischemic (HI) injuries of the developing brain. The present study investigated the effect of hyperthermic PT on HI brain injuries in newborn rats. Methods : HI was produced in 7-day-old neonatal rats by unilateral common carotid artery ligation, followed by hypoxia with 8% oxygen at $38^{\circ}C$ for 2 hours. Twenty-four hours before HI, one-half of the pups were exposed to a $40^{\circ}C$ environment for 2 hours. The severity of the brain injury was assessed 7 days after the HI. Results : Hyperthermic PT reduced the gross and histopathologic findings of brain injury from 64.7 to 31.2% (P<0.05). There were no differences in location and severity of injury between the pretreated and control brains. Conclusion : These findings indicate that hyperthermic PT provides neuroprotective benefits on HI in the developing brain. Also, these findings suggest maternal hyperthermia may have protective effect on perinatal HI brain injuries.

• Clinical and Experimental Pediatrics
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• v.51 no.10
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• pp.1102-1111
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• 2008

Purpose : Resveratrol, extracted from red wine and grapes, has an anti-cancer effect, an antiinflammatory effect, and an antioxidative effect mainly in heart disease and also has neuroprotective effects in the adult animal model. No studies for neuroprotective effects during the neonatal periods have been reported. Therefore, we studied the neuroprotective effect of resveratrol on hypoxic-ischemic brain damage in neonatal rats via anti-apoptosis. Methods : Embryonic cortical neuronal cell culture of rat brain was performed using pregnant Sprague-Dawley (SD) rats at 18 days of gestation (E18) for the in vitro approach. We injured the cells with hypoxia and administered resveratrol (1, 10, and $30{\mu}g/mL$) to the cells at 30 minutes before hypoxic insults. In addition, unilateral carotid artery ligation with hypoxia was induced in 7-day-old neonatal rats for the in vivo approach. We injected resveratrol (30 mg/kg) intraperitoneally into animal models. Real-time PCR and Western blotting were performed to identify the neuroprotective effects of resveratrol through anti-apoptosis. Results : In the in vitro approach of hypoxia, the expression of Bax, caspase-3, and the ratio of Bax/Bcl-2, indicators of the level of apoptosis, were significantly increased in the hypoxia group compared to the normoxia group. In the case of the resveratrol-treated group, expression was significantly decreased compared to the hypoxia group. And the results in the in vivo approach were the same as in the in vitro approach. Conclusion : The present study demonstrates that resveratrol plays neuroprotective role in hypoxic-ischemic brain damage during neonatal periods through the mechanism of anti-apoptosis.