• 한국방사선학회논문지
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• 제8권7호
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• pp.389-395
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• 2014

본 연구는 교모세포종 (Glioblastoma multiform, GBM)에 대한 방사선 진단학적/치료학적 연구에 필수적으로 필요한 악성뇌종양 동물모델을 개발하기 위해 수행되었다. 악성뇌종양 동물모델 개발을 위해 뇌정위 기구(stereotactic instrument)를 이용하여 C6 세포(Glioblastoma cell line)를 SD rat의 우측 선조체 내에 동종이식하였다. 개발된 동물모델의 검증을 위해 MRI와 해부조직학적 검사방법을 이용하였다. 해부조직학적 검사방법으로는 H&E 염색법을 이용하였다. MRI를 이용한 종양 형성 검사에서 C6 세포 이식 7일 후 종양 형성이 확인되었고, 14일 후에는 이식한 우측 뇌의 대부분이 종양으로 변화한 것을 확인하였다. 해부조직학적 검사에서는 과세포 발현 및 다형성 세포에 의해 형태학적 변화가 발생하는 것을 알 수 있었다. 본 연구에서 개발된 악성뇌종양 동물모델은 in vivo level에서 교모세포종에 대한 방사선 진단학적 기술 개발 및 새로운 치료법 개발을 위한 필수적인 도구로서 활용될 수 있을 것이다.

• Journal of Ginseng Research
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• 제40권2호
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• pp.196-202
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• 2016

Background: Ginsenoside Rd (GSRd), a main component of the root of Panax ginseng, exhibits anti-inflammation functions and decreases infarct size in many injuries and ischemia diseases such as focal cerebral ischemia. M1 Macrophages are regarded as one of the key inflammatory cells having functions for disease progression. Methods: To investigate the effect of GSRd on renal ischemia/reperfusion injury (IRI) and macrophage functional status, and their regulatory role on mouse polarized macrophages in vitro, GSRd (10-100 mg/kg) and vehicle were applied to mice 30 min before renal IRI modeling. Renal functions were reflected by blood serum creatinine and blood urea nitrogen level and histopathological examination. M1 polarized macrophages infiltration was identified by flow cytometry analysis and immunofluorescence staining with $CD11b^+$, $iNOS^+$/interleukin-12/tumor necrosis factor-${\alpha}$ labeling. For the in vitro study, GSRd ($10-100{\mu}g/mL$) and vehicle were added in the culture medium of M1 macrophages to assess their regulatory function on polarization phenotype. Results: In vivo data showed a protective role of GSRd at 50 mg/kg on Day 3. Serum level of serum creatinine and blood urea nitrogen significantly dropped compared with other groups. Reduced renal tissue damage and M1 macrophage infiltration showed on hematoxylin-eosin staining and flow cytometry and immunofluorescence staining confirmed this improvement. With GSRd administration, in vitro cultured M1 macrophages secreted less inflammatory cytokines such as interleukin-12 and tumor necrosis factor-${\alpha}$. Furthermore, macrophage polarization-related pancake-like morphology gradually changed along with increasing concentration of GSRd in the medium. Conclusion: These findings demonstrate that GSRd possess a protective function against renal ischemia/reperfusion injury via downregulating M1 macrophage polarization.

• 대한수의학회지
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• 제20권1호
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• pp.65-78
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• 1980

From November 1978 to April 1979, there occurred among cows many cases of abortion, premature birth, stillbirth and congenital arthrogryposis or hydranencephaly in Kyongki-do province in Korea. Epizootics recurred between February and May, 1980 in the same area. Six calves born at 8 or 10 months of gestation were examined by means of pathology and one of the calves was examined by serological test. And a survey on local occurrence of the disease in other than Kyongki-do province, was conducted. 1. At necropsy, some calves showed distinct lesions such deformities of the limbs and the vertebrae as arthrogryposis or scoliosis. Other calves revealed arthrogryposis and partial or total deficience of the cerebral hemispheres with hydranencephaly. 2. In the calves with deformities the skeletal muscle showed histologically severe hypoplasia of the muscle fibers with cellular infiltration. In the central nervous system of the calves with hydranencephaly there were minute cystic cavitation and the decrease of ventral horn cells of the spinal cord in the number. 3. Similar epizootics were also observed in the same season in the other several provinces such as Chungoheongnam-do, Kangwon-do and Jeonrabuk-do. 4. Anti-Akabane virus antibody was detected in precolostral blood from the calf with arthroglposis and hydranencephaly syndrome. 5. On these findings of the disease it was diagnosed as Akabane disease presenting the first report on the epizootics in Korea.

• Animal cells and systems
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• 제1권1호
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• pp.107-113
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• 1997

Antisera against the myotropic neuropeptide leucokinin I, originally isolated from head extracts of the cockroach Leucophaea maderae, have been used to investigate the distribution of the leucokinin I-immunoreactive (LK I-IR) neurons in the brain of the common cutworm, Spodoptera Iitura, during postembryonic development. The LK I-IR neurons are found at the larval stages (excluding first instar larval stage), pupal stages, and adult stage, of which the brains have been examined in this experiment. The number of the LK I-IR neurons in the brain increases from the second instar larva to the fifth instar larva which has about 32, the largest number in all postembryonic stages. Thereafter, the LK I-IR neurons begin to decrease in number. During the pupal stages, smaller number of LK I-IR neurons persist in the brains; 6 or 4. At adult stage the brain contains 8 LK I-IR neurons. The LK I-IR cell bodies are distributed in each dorsal cortex of both cerebral hemispheres in the second instar larva and through all the neuromeres of the brain during later larval stages, despite of being a large number of the LK I-IR cell bodies in dorsolateral neuromeres. At pupal stages, most of the LK I-IR cell bodies are found in the pars intercerebralis. Extremely small number of the LK I-IR cell bodies are localized in the pars lateral is. Adult brain contains the LK I-IR cell bodies in the pars intercerebralis and the middle cortex of the posterior brain. The LK I-IR nerve processes can be easily found in the neuropils of almost all the neuromeres in the brains of third, fourth, fifth and sixth instar larvae. Most of the LK I-IR nerve fibers in those brains are originated from the LK I-IR cell bodies located in the brains. The LK I-IR cell bodies which have very weak reactivities to the antisera do not show projection of the LK I-IR nerve processes in the brains.

• 대한수의학회지
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• 제39권3호
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• pp.531-537
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• 1999

The present study was carried out to investigate the pathogenicity and pathogenesis of wild rats(Rattus norvegicus), trapped in nature, intranasally infected with Aujeszky's disease virus(ADV/NYJ-1-87) by histopathology, immunohistochemistry and in situ hybridization(ISH). Fifteen rats inoculated intranasally were roughened haircoat, anorexia, listlessness, and depression second day after inoculation, and three rats died in 66-72 hours. Eight rats showed severe pruritus at the face that was accompanied by frequent face-washing movements of the forelegs, and then became violent and spasmodic for an hour or until they died. Four rats slowly recovered after showing mild clinical signs of the disease. Microscopic lesions in infected rats were characterized by meningitis, perivascular round cell infiltration, focal gliosis, and neuronal degeneration and necrosis. And intranuclear inclusion bodies were frequently detected in the cerebral cortex and medulla. Positive reaction to ADV by immunohistochemistry and ISH were detected in the following areas : trigermimal ganglion, brain, tonsil, nasal mucosa, spleen, lung and liver. The result has suggested that ADV intranasally infected in wild rats is followed by replication in epithelial calls of nasal mucosa and tonsil, then invade local lymph nodes by way of the lymphatics. It is also believed that the virus invades bipolar olfactory cells and trigerminal ganglion; and then spread into central nervous system.

• Molecules and Cells
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• 제19권3호
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• pp.356-364
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• 2005

Intramolecular excimer formation of 1,3-di(1-pyrenyl) propane(Py-3-Py) and fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH) were used to evaluate the effect of ethanol on the rate and range of lateral and rotational mobilities of bulk bilayer structures of synaptosomal plasma membrane vesicles (SPMVs) from the bovine cerebral cortex. Ethanol increased the excimer to monomer fluorescence intensity ratio (I'/I) of Py-3-Py in the SPMVs. Selective quenching of both DPH and Py-3-Py by trinitrophenyl groups was used to examine the range of transbilayer asymmetric rotational mobility and the rate and range of transbilayer asymmetric lateral mobility of SPMVs. Ethanol increased the rotational and lateral mobility of the outer monolayer more than of the inner one. Thus ethanol has a selective fluidizing effect within the transbilayer domains of the SPMVs. Radiationless energy transfer from the tryptophans of membrane proteins to Py-3-Py was used to examine both the effect of ethanol on annular lipid fluidity and protein distribution in the SPMVs. Ethanol increased annular lipid fluidity and also caused membrane proteins to cluster. These effects on neuronal membranes may be responsible for some, though not all, of the general anesthetic actions of ethanol.

• Molecules and Cells
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• 제39권6호
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• pp.501-507
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• 2016

The corpus callosum is a bundle of nerve fibers that connects the two cerebral hemispheres and is essential for coordinated transmission of information between them. Disruption of early stages of callosal development can cause agenesis of the corpus callosum (AgCC), including both complete and partial callosal absence, causing mild to severe cognitive impairment. Despite extensive studies, the etiology of AgCC remains to be clarified due to the complicated mechanism involved in generating AgCC. The biological function of PI3K signaling including phosphatidylinositol-3,4,5-trisphosphate is well established in diverse biochemical processes including axon and dendrite morphogenesis, but the function of the closely related phosphatidylinositol-3,4,-bisphosphate (PI(3,4)P2) signaling, particularly in the nervous system, is largely unknown. Here, we provide the first report on the role of inositol polyphosphate 4-phosphatase II (INPP4B), a PI(3,4)P2 metabolizing 4-phosphatase in the regulation of callosal axon formation. Depleting INPP4B by in utero electroporation suppressed medially directed callosal axon formation. Moreover, depletion of INPP4B significantly attenuated formation of Satb2-positive pyramidal neurons and axon polarization in cortical neurons during cortical development. Taken together, these data suggest that INPP4B plays a role in the regulating callosal axon formation by controlling axon polarization and the Satb2-positive pyramidal neuron population. Dysregulation of INPP4B during cortical development may be implicated in the generation of partial AgCC.

• Molecules and Cells
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• 제37권11호
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• pp.767-776
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• 2014

Alzheimer's disease (AD) is clinically characterized with progressive memory loss and cognitive decline. Synaptic dysfunction is an early pathological feature that occurs prior to neurodegeneration and memory dysfunction. Mounting evidence suggests that aggregation of amyloid-${\alpha}$ ($A{\alpha}$) and hyperphosphorylated tau leads to synaptic deficits and neurodegeneration, thereby to memory loss. Among the established genetic risk factors for AD, the ${\varepsilon}4$ allele of apolipoprotein E (APOE) is the strongest genetic risk factor. We and others previously demonstrated that apoE regulates $A{\alpha}$ aggregation and clearance in an isoform-dependent manner. While the effect of apoE on $A{\alpha}$ may explain how apoE isoforms differentially affect AD pathogenesis, there are also other underexplored pathogenic mechanisms. They include differential effects of apoE on cerebral energy metabolism, neuroinflammation, neurovascular function, neurogenesis, and synaptic plasticity. ApoE is a major carrier of cholesterols that are required for neuronal activity and injury repair in the brain. Although there are a few conflicting findings and the underlying mechanism is still unclear, several lines of studies demonstrated that apoE4 leads to synaptic deficits and impairment in long-term potentiation, memory and cognition. In this review, we summarize current understanding of apoE function in the brain, with a particular emphasis on its role in synaptic plasticity and the underlying cellular and molecular mechanisms, involving low-density lipoprotein receptor-related protein 1 (LRP1), syndecan, and LRP8/ApoER2.

• The Korean Journal of Physiology and Pharmacology
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• 제2권3호
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• pp.279-286
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• 1998

It has been well documented that transient forebrain global ischemia causes selective neuronal degeneration in hippocampal CA1 pyramidal neurons with a delay of a few days. The mechanism of this delayed hippocampal CA1 pyramidal neuronal death (DND) is still controversial. To delineate the mechanisms of the DND, the effects of treatment with MK-801, an NMDA receptor antagonist, kynurenic acid, a NMDA/non-NMDA receptor antagonist, and/or cycloheximide, a protein synthesis inhibitor, on the DND were investigated in male Wistar rats. To examine the participation of apoptotic neuronal death in the DND, TUNEL staining was performed in ischemic brain section. Global ischemia was induced by 4-vessel occlusion for 20 min. All animals in this study showed the DND 3 and 7 days after the ischemic insult. The DND that occured 3 days and 7 days after the ischemia were not affected by pretreatment with MK-801 (1 mg/kg), but markedly attenuated by the pretreatment with kynurenic acid (500 mg/kg). Treatment with cycloheximide (1 mg/kg) also markedly inhibited the DND. The magnitudes of attenuation by the two drugs were similar. The magnitude of attenuation by co-treatments with kynurenic acid and cycloheximide was not greater than that with any single treatment. TUNEL staining was negative in the sections obtained 1 or 2 days after the ischemic insults, but it was positive at hippocampal CA1 pyramidal cells in sections collected 3 days after the ischemia. These results suggested that the DND should be mediated by the activation of non-NMDA receptor, not by the activation of NMDA receptor and that the activation of AMPA receptor should induce the apoptotic process in the DND.

• Parasites, Hosts and Diseases
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• 제59권3호
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• pp.189-225
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• 2021

The use of albendazole and mebendazole, i.e., benzimidazole broad-spectrum anthelmintics, in treatment of parasitic infections, as well as cancers, is briefly reviewed. These drugs are known to block the microtubule systems of parasites and mammalian cells leading to inhibition of glucose uptake and transport and finally cell death. Eventually they exhibit ovicidal, larvicidal, and vermicidal effects on parasites, and tumoricidal effects on hosts. Albendazole and mebendazole are most frequently prescribed for treatment of intestinal nematode infections (ascariasis, hookworm infections, trichuriasis, strongyloidiasis, and enterobiasis) and can also be used for intestinal tapeworm infections (taeniases and hymenolepiasis). However, these drugs also exhibit considerable therapeutic effects against tissue nematode/cestode infections (visceral, ocular, neural, and cutaneous larva migrans, anisakiasis, trichinosis, hepatic and intestinal capillariasis, angiostrongyliasis, gnathostomiasis, gongylonemiasis, thelaziasis, dracunculiasis, cerebral and subcutaneous cysticercosis, and echinococcosis). Albendazole is also used for treatment of filarial infections (lymphatic filariasis, onchocerciasis, loiasis, mansonellosis, and dirofilariasis) alone or in combination with other drugs, such as ivermectin or diethylcarbamazine. Albendazole was tried even for treatment of trematode (fascioliasis, clonorchiasis, opisthorchiasis, and intestinal fluke infections) and protozoan infections (giardiasis, vaginal trichomoniasis, cryptosporidiosis, and microsporidiosis). These drugs are generally safe with few side effects; however, when they are used for prolonged time (>14-28 days) or even only 1 time, liver toxicity and other side reactions may occur. In hookworms, Trichuris trichiura, possibly Ascaris lumbricoides, Wuchereria bancrofti, and Giardia sp., there are emerging issues of drug resistance. It is of particular note that albendazole and mebendazole have been repositioned as promising anti-cancer drugs. These drugs have been shown to be active in vitro and in vivo (animals) against liver, lung, ovary, prostate, colorectal, breast, head and neck cancers, and melanoma. Two clinical reports for albendazole and 2 case reports for mebendazole have revealed promising effects of these drugs in human patients having variable types of cancers. However, because of the toxicity of albendazole, for example, neutropenia due to myelosuppression, if high doses are used for a prolonged time, mebendazole is currently more popularly used than albendazole in anti-cancer clinical trials.