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Animal Models of Periventricular Leukomalacia.

Ehn Kyoung CHOI ; Dongsun PARK ; Tae Kyun KIM ; Sun Hee LEE ; Dae Kwon BAE ; Goeun YANG ; Yun Hui YANG ; Jangbeen KYUNG ; Dajeong KIM ; Woo Ryoung LEE ; Jun Gyo SUH ; Eun Suk JEONG ; Seung U KIM ; Yun Bae KIM

Laboratory Animal Research.2011;27(2):77-84. doi:10.5625/lar.2011.27.2.77

Periventricular leukomalacia, specifically characterized as white matter injury, in neonates is strongly associated with the damage of pre-myelinating oligodendrocytes. Clinical data suggest that hypoxia-ischemia during delivery and intrauterine or neonatal infection-inflammation are important factors in the etiology of periventricular leukomalacia including cerebral palsy, a serious case exhibiting neurobehavioral deficits of periventricular leukomalacia. In order to explore the pathophysiological mechanisms of white matter injury and to better understand how infectious agents may affect the vulnerability of the immature brain to injury, novel animal models have been developed using hypoperfusion, microbes or bacterial products (lipopolysaccharide) and excitotoxins. Such efforts have developed rat models that produce predominantly white matter lesions by adopting combined hypoxia-ischemia technique on postnatal days 1-7, in which unilateral or bilateral carotid arteries of animals are occluded (ischemia) followed by 1-2 hour exposure to 6-8% oxygen environment (hypoxia). Furthermore, low doses of lipopolysaccharide that by themselves have no adverse-effects in 7-day-old rats, dramatically increase brain injury to hypoxic-ischemic challenge, implying that inflammation sensitizes the immature central nervous system. Therefore, among numerous models of periventricular leukomalacia, combination of hypoxia-ischemia-lipopolysaccharide might be one of the most-acceptable rodent models to induce extensive white matter injury and ensuing neurobehavioral deficits for the evaluation of candidate therapeutics.
Animals ; Brain ; Brain Injuries ; Carotid Arteries ; Central Nervous System ; Cerebral Palsy ; Humans ; Infant, Newborn ; Inflammation ; Leukomalacia, Periventricular ; Models, Animal ; Neurotoxins ; Oligodendroglia ; Oxygen ; Rats ; Rodentia

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Pathomorphological features of calcinosis circumscripta in a dog.

Eun Mi LEE ; Ah Young KIM ; Eun Joo LEE ; Kyu Shik JEONG

Laboratory Animal Research.2016;32(1):74-77. doi:10.5625/lar.2016.32.1.74

A 19-month-old male German shepherd dog was presented with a hindlimb footpad mass. The mass was excised and histopathology was performed. Grossly, the cut section of the mass had multiple well-circumscribed nodules with a chalky appearance. Histopathologically, basophilic-stained calcium deposits of various sizes were distributed from dermis to subcutis, surrounded by epithelioid cells, multinucleated giant cells, and reactive fibroblasts. Myxoid metaplasia, calcium deposits in hair follicles, and psammoma-like bodies were also found. These histopathologic observations will greatly help to understand the pathogenesis of calcinosis circumscripta.
Animals ; Calcinosis* ; Calcium ; Dermis ; Dogs* ; Epithelioid Cells ; Fibroblasts ; Giant Cells ; Hair Follicle ; Hindlimb ; Humans ; Infant ; Male ; Metaplasia

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Rapid and efficient identification of the mouse leptin receptor mutation (C57BL/KsJ-db/db) by tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) analysis.

Harry JUNG ; Hajin NAM ; Jun Gyo SUH

Laboratory Animal Research.2016;32(1):70-73. doi:10.5625/lar.2016.32.1.70

The C57BLKS/J-Lepr(db) mouse has a point mutation in the leptin receptor gene and is one of the most useful animal model for non-insulin dependent diabetes mellitus in human. Since the homozygote of C57BLKS/J-Lepr(db) mouse is infertile, detection of point mutation in the leptin receptor gene is important for efficient maintaining strains as well as mass production of homozygotes. To develop a rapid and efficient genotyping method for C57BLKS/J-Lepr(db) mouse, the tetra-primer amplification-refractory mutation system polymerase chain reaction (ARMS-PCR) was used. The 407 and 199 bp PCR products were amplified from normal (+/+) mice; while the 407 and 268 bp PCR products were amplified from homozygotes (db/db) mice; and the 407, 268, and 199 bp PCR products were amplified from heterozygotes (db/+) mice. This result showed that the tetra-primer ARMS-PCR analysis by us is suitable to detect point mutation of the leptin receptor gene. Taken together, our method will dramatically reduce animal use for maintenance of strains as well as production of homozygote in the C57BLKS/J-Lepr(db) strains.
Animals ; Diabetes Mellitus ; Heterozygote ; Homozygote ; Humans ; Leptin* ; Mice* ; Models, Animal ; Point Mutation ; Polymerase Chain Reaction ; Receptors, Leptin*

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Anticoccidial effects of the Plantago asiatica extract on experimental Eimeria tenella infection.

Sunhwa HONG ; Gi Wook OH ; Won Guk KANG ; Okjin KIM

Laboratory Animal Research.2016;32(1):65-69. doi:10.5625/lar.2016.32.1.65

Anticoccidial effects of the Plantago asiatica extract (PAE) were evaluated in chickens following oral infection with Eimeria (E.) tenella. This study was conducted on the 3-day-old chickens (n=30). Those animals were divided with 3 groups; PAE 0.1% treated/infected (n=10), PAE untreated/infected (n=10) and non-infected control (n=10). Chickens were fed a standard diet supplemented with or without PAE for 1 week prior to infection with E. tenella (10,000 sporulated oocysts per chicken). The effects of PAE on E. tenella infection were assessed by two parameters; fecal oocysts shedding and body weights gain. The PAE-fed chickens produced significantly reduced fecal oocysts (P<0.05) when compared to the E. tenella-infected group fed standard diet. Also, PAE-based diet, improved body weight loss caused by E. tenella infection. Our data demonstrated that PAE had remarkable anticoccidial activities against E. tenella. This finding might have implications for the development of anticoccidial drug. This study is the first to demonstrate anticoccidial effect of PAE on Eimeria parasites.
Animals ; Body Weight ; Chickens ; Diet ; Eimeria tenella* ; Eimeria* ; Oocysts ; Parasites ; Plantago*

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Comparison of the response using ICR mice derived from three different sources to ethanol/hydrochloric acid-induced gastric injury.

Sung Hwa SONG ; Ji Eun KIM ; Jun GO ; Eun Kyoung KOH ; Ji Eun SUNG ; Hyun Ah LEE ; Kyung Min CHOI ; Hae Deun KIM ; Young Suk JUNG ; Kil Soo KIM ; Dae Youn HWANG

Laboratory Animal Research.2016;32(1):56-64. doi:10.5625/lar.2016.32.1.56

Animal models for gastric ulcers produced by physical, pharmacological and surgical methods have been widely employed to evaluate therapeutic drugs and investigate the mechanism of action of this disease. ICR mice were selected to produce this model, even though several mice and rats have been widely used in studies of gastric ulcers. To compare the responses of ICR mice obtained from three different sources to gastric ulcer inducers, alterations in gastric injury, histopathological structure, and inflammation were measured in Korl:ICR (Korea NIFDS source), A:ICR (USA source) and B:ICR (Japan source) treated with three concentrations of ethanol (EtOH) (50, 70, and 90%) in 150 mM hydrochloric acid (HCl) solution. Firstly, the stomach lesion index gradually increased as the EtOH concentration increased in three ICR groups. Moreover, a significant increase in the level of mucosal injury, edema and the number of inflammatory cells was similarly detected in the EtOH/HCl treated group compared with the vehicle treated group in three ICR groups. Furthermore, the number of infiltrated mast cells and IL-1β expression were very similar in the ICR group derived from three different sources, although some differences in IL-1β expression were detected. Especially, the level of IL-1β mRNA in 50 and 90EtOH/HCl treated group was higher in Korl:ICR and A:ICR than B:ICR. Overall, the results of this study suggest that Korl:ICR, A:ICR and B:ICR derived from different sources have an overall similar response to gastric ulcer induced by EtOH/HCl administration, although there were some differences in the magnitude of their responses.
Animals ; Edema ; Ethanol ; Hydrochloric Acid ; Inflammation ; Mast Cells ; Mice ; Mice, Inbred ICR* ; Models, Animal ; Rats ; RNA, Messenger ; Stomach ; Stomach Ulcer

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Reference values of hematology, biochemistry, and blood type in cynomolgus monkeys from cambodia origin.

Kangmoo CHOI ; Jaejin CHANG ; Min Jae LEE ; Seungsu WANG ; Kimhong IN ; Wilhelm C GALANO-TAN ; Sanghun JUN ; Kahee CHO ; Yong Hwa HWANG ; Sung Ju KIM ; Wanje PARK

Laboratory Animal Research.2016;32(1):46-55. doi:10.5625/lar.2016.32.1.46

Cynomolgus monkeys as nonhuman primates are valuable animal models because they have a high level of human gene homology. There are many reference values for hematology and biochemistry of Cynomolgus monkeys that are needed for proper clinical diagnosis and biomedical research conduct. The body weight information and blood type are also key success factors in allogeneic or xenogeneic models. Moreover, the biological parameters could be different according to the origin of the Cynomolgus monkey. However, there are limited references provided, especially of Cambodia origin. In this study, we measured average body weight of 2,518 Cynomolgus monkeys and analyzed hematology and serum biochemistry using 119 males, and determined blood types in 642 monkeys with Cambodia origin. The average body weight of male Cynomolgus monkeys were 2.56±0.345 kg and female group was 2.43±0.330 kg at the age from 2 to 3 years. The male group showed relatively sharp increased average body weight from the 3 to 4 age period compared to the female group. In hematology and biochemistry, it was found that most of the data was similar when compared to other references even though some results showed differences. The ABO blood type result showed that type A, B, AB, and O was approximately 15.6, 33.3, 44.2, and 6.9%, respectively. The main blood type in this facility was B and AB. These biological background references of Cambodia origin could be used to provide important information to researchers who are using them in their biomedical research.
Biochemistry* ; Body Weight ; Cambodia* ; Diagnosis ; Female ; Haplorhini ; Hematology* ; Humans ; Macaca fascicularis* ; Male ; Models, Animal ; Primates ; Reference Values*

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Therapeutic effect of ethyl acetate extract from Asparagus cochinchinensis on phthalic anhydride-induced skin inflammation.

Ji Eun SUNG ; Hyun Ah LEE ; Ji Eun KIM ; Jun GO ; Eun Ji SEO ; Woo Bin YUN ; Dong Seob KIM ; Hong Joo SON ; Chung Yeoul LEE ; Hee Seob LEE ; Dae Youn HWANG

Laboratory Animal Research.2016;32(1):34-45. doi:10.5625/lar.2016.32.1.34

Asparagus cochinchinensis has been used to treat various diseases including fever, cough, kidney disease, breast cancer, inflammatory disease and brain disease, while IL-4 cytokine has been considered as key regulator on the skin homeostasis and the predisposition toward allergic skin inflammation. However, few studies have investigated its effects and IL-4 correlation on skin inflammation to date. To quantitatively evaluate the suppressive effects of ethyl acetate extracts of A. cochinchinensis (EaEAC) on phthalic anhydride (PA)-induced skin inflammation and investigate the role of IL-4 during their action mechanism, alterations in general phenotype biomarkers and luciferase-derived signals were measured in IL-4/Luc/CNS-1 transgenic (Tg) mice with PA-induced skin inflammation after treatment with EaEAC for 2 weeks. Key phenotype markers including lymph node weight, immunoglobulin E (IgE) concentration, epidermis thickness and number of infiltrated mast cells were significantly decreased in the PA+EaEAC treated group compared with the PA+Vehicle treated group. In addition, expression of IL-1β and TNF-α was also decreased in the PA+EaEAC cotreated group, compared to PA+Vehicle treated group. Furthermore, a significant decrease in the luciferase signal derived from IL-4 promoter was detected in the abdominal region, submandibular lymph node and mesenteric lymph node of the PA+EaEAC treated group, compared to PA+Vehicle treated group. Taken together, these results suggest that EaEAC treatment could successfully improve PA-induced skin inflammation of IL-4/Luc/CNS-1 Tg mice, and that IL-4 cytokine plays a key role in the therapeutic process of EaEAC.
Animals ; Biomarkers ; Brain Diseases ; Cough ; Epidermis ; Fever ; Homeostasis ; Immunoglobulin E ; Immunoglobulins ; Inflammation* ; Inflammatory Breast Neoplasms ; Interleukin-4 ; Kidney Diseases ; Luciferases ; Lymph Nodes ; Mast Cells ; Mice ; Phenotype ; Skin*

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Role of mitogen-activated protein kinases and nuclear factor-kappa B in 1,3-dichloro-2-propanol-induced hepatic injury.

In Chul LEE ; Sang Min LEE ; Je Won KO ; Sung Hyeuk PARK ; In Sik SHIN ; Changjong MOON ; Sung Ho KIM ; Jong Choon KIM

Laboratory Animal Research.2016;32(1):24-33. doi:10.5625/lar.2016.32.1.24

In this study, the potential hepatotoxicity of 1,3-dichloro-2-propanol and its hepatotoxic mechanisms in rats was investigated. The test chemical was administered orally to male rats at 0, 27.5, 55, and 110 mg/kg body weight. 1,3-Dichloro-2-propanol administration caused acute hepatotoxicity, as evidenced by an increase in serum aminotransferases, total cholesterol, and total bilirubin levels and a decrease in serum glucose concentration in a dose-dependent manner with corresponding histopathological changes in the hepatic tissues. The significant increase in malondialdehyde content and the significant decrease in glutathione content and antioxidant enzyme activities indicated that 1,3-dichloro-2-propanol-induced hepatic damage was mediated through oxidative stress, which caused a dose-dependent increase of hepatocellular apoptotic changes in the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay and immunohistochemical analysis for caspase-3. The phosphorylation of mitogen-activated protein kinases caused by 1,3-dichloro-2-propanol possibly involved in hepatocellular apoptotic changes in rat liver. Furthermore, 1,3-dichloro-2-propanol induced an inflammatory response through activation of nuclear factor-kappa B signaling that coincided with the induction of pro-inflammatory mediators or cytokines in a dose-dependent manner. Taken together, these results demonstrate that hepatotoxicity may be related to oxidative stress-mediated activation of mitogen-activated protein kinases and nuclear factor-kappa B-mediated inflammatory response.
Animals ; Bilirubin ; Blood Glucose ; Body Weight ; Caspase 3 ; Cholesterol ; Cytokines ; Glutathione ; Humans ; Liver ; Male ; Malondialdehyde ; Mitogen-Activated Protein Kinases* ; Oxidative Stress ; Phosphorylation ; Rats ; Transaminases

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Laxative effects of Liriope platyphylla are tightly correlated with suppression of endoplasmic reticulum stress in loperamide-induced constipation of SD rats.

Ji Eun KIM ; Jun GO ; Ji Eun SUNG ; Hyun Ah LEE ; Eun Ji SEO ; Woo Bin YUN ; Dae Youn HWANG

Laboratory Animal Research.2016;32(1):16-23. doi:10.5625/lar.2016.32.1.16

A dysfunction of endoplasmic reticulum (ER) stress response can result in various diseases, including cancer, inflammation, diabetes and neurodegenerative disorders. To investigate whether ER stress response can play an essential role in the induction and treatment of chronic constipation, alterations in the key parameters for ER stress were measured in loperamide (Lop) induced constipation Sprague Dawley (SD) rats treated with aqueous extracts of Liriope platyphylla (AEtLP), which has been shown to have a laxative effect. Symptoms of chronic constipation including alteration of stool parameters and the transverse colon's structure were successfully induced by Lop treatment. Laxative effects such as enhancement of stools parameters, recovery of the mucosa thickness, increased muscle thickness and recovery of flat luminal surface were also observed in the Lop+AEtLP treated group. Furthermore, enhancement of eukaryotic initiation factor 2 alpha (eIF2α) phosphorylation and inositol-requiring enzyme 1 beta (IRE1β) expression, key indicators for ER stress, that were observed in the Lop+vehicle treated group were significantly recovered in the Lop+AEtLP treated group, although the phosphorylation level of c-Jun N-terminal protein kinase (JNK) remained constant. Moreover, alterations in the transcription level of the marker genes X-box binding protein 1 (XBP-1) and growth arrest and DNA damage-inducible protein (GADD34) were similar to those of eIF2α and IRE1β. However, their level was slightly or completely recovered after AEtLP treatment. Overall, this study provides the first evidence that ER stress response may be tightly correlated with chronic constipation induced by Lop treatment, as well as the laxative effects of AEtLP.
Animals ; Carrier Proteins ; Constipation* ; DNA ; Endoplasmic Reticulum Stress* ; Endoplasmic Reticulum* ; Eukaryotic Initiation Factor-2 ; Inflammation ; Loperamide ; Mucous Membrane ; Neurodegenerative Diseases ; Phenobarbital ; Phosphorylation ; Protein Kinases ; Rats*

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Cardiopulmonary effects of thiopental versus propofol as an induction agent prior to isoflurane anesthesia in chair trained rhesus macaques (Macaca mulatta).

Yun Jung CHOI ; Hye Jin PARK ; Hyeon Ho KIM ; Yun Jin LEE ; Kyeong Cheon JUNG ; Seong Hoe PARK ; Jae Il LEE

Laboratory Animal Research.2016;32(1):8-15. doi:10.5625/lar.2016.32.1.8

The purpose of this study was to evaluate the effects of thiopental versus propofol on cardiopulmonary functions, when used as an induction agent prior to isoflurane anesthesia in rhesus monkeys. Eight healthy rhesus monkeys weighing 3.72 to 5.7 kg, 4-5 years old, were used in the study. Anesthesia was induced with thiopental or propofol intravenous injection, and then maintained with isoflurane in oxygen for 45 minutes. Cardiopulmonary measurements were obtained before and 5, 15, 30, 45, and 60 minutes after induction. The induction doses of thiopental and propofol were 19.41±0.54 and 9.33±1.02 mg/kg, respectively. In both groups, the values of heart rate, respiratory rate, temperature, systolic blood pressure, mean blood pressure, diastolic blood pressure, pH, and lactate were decreased, while the values of partial pressure of carbon dioxide, partial pressure of oxygen, total carbon dioxide, bicarbonate, oxygen saturation, and base excess in the extracellular fluid were increased, as compared with baseline. Systolic blood pressure was significantly lower in thiopental group compare to propofol group. Induction time was very short in both agents but not revealed a significant difference between both groups. However, recovery time was extremely faster in the propofol group. Our results demonstrated that propofol provides a minor suppression in systolic arterial blood pressure than thiopental sodium. In addition, propofol have a fast recovery effect from the anesthesia as well. Furthermore, it is suggested that thiopental sodium could also be used to induce anesthesia instead of propofol, despite slight more suppression of cardiopulmonary function compared to thiopental sodium.
Anesthesia* ; Arterial Pressure ; Blood Pressure ; Carbon Dioxide ; Extracellular Fluid ; Heart Rate ; Hydrogen-Ion Concentration ; Injections, Intravenous ; Isoflurane* ; Lactic Acid ; Macaca mulatta* ; Oxygen ; Partial Pressure ; Propofol* ; Respiratory Rate ; Thiopental*

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