• Biomedical Science Letters
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• v.12 no.2
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• pp.81-89
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• 2006

The ischemia-responsive 94 gene (irp94) encoding a 94 kDa endoplasmic reticulum resident protein was investigated its molecular properties associated with unfoled protein responses. First, the expression of irp94 mRNA was tested after the reperfusion of the transient forebrain ischemia induction at the central nervous system in three Mongolian gerbils. Second, irp94 expression in PC12 cells, which are derived from transplantable rat pheochromocytoma cultured in the DMEM media, was tested at transcriptional and translational levels. The half life of irp94 mRNA was also determined In PC12 cells. Last, the changes of irp94 mRNA expression were investigated by the addition of various ER stress inducible chemicals (A23187, BFA, tunicamycin, DTT and $H_2O_2$) and proteasome inhibitors, and heat shock. High level expression of irp94 mRNA was detected after 3 hours reperfusion in the both sites of the cerebral cortex and hippocampus of the gerbil brain. The main regulation of irp94 mRNA expression in PC 12 cells was determined at the transcriptional level. The half life of irp94 mRNA in PC12 cells was approximately 5 hours after the initial translation. The remarkable expression of irp94 mRNA was detected by the treatment of tunicamycin, which blocks glycosylation of newly synthesized polypeptides, and $H_2O_2$, which induces apoptosis. When PC12 cells were treated with the cytosol proteasome inhibitors such as ALLN (N-acetyl-leucyl-norleucinal) and MG 132 (methylguanidine), irp94 mRNA expression was increased. These results indicate that expression of irp94 was induced by ER stress including oxidation condition and glycosylation blocking in proteins. Expression of irp94 was increased when the cells were chased after heat shock, suggesting that irp94 may be involved in recovery rather than protection against ER stresses. In addition, irp94 expression was remarkably increased when cytosol proteasomes were inhibited by ALLN and MG 132, suggesting that irp94 plays an important role for maintaining the ERAD (endoplasmic reticulum associated degradation) function.

• Journal of Veterinary Clinics
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• v.27 no.2
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• pp.186-189
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• 2010

A 14-year-old neutered female Chihuahua was presented because of seizure episodes and circling to the left side. Based on neurological examination, the lesion was localized on left forebrain. The mass in the left nasal cavity and breaching of the nasal septum were seen magnetic resonance images. And there was a presence of contrast enhanced mass involving the rostral left brain. Based on diagnostic image analysis, this lesion strongly suggested secondary brain tumor infiltrated by nasal cavity. The patient's symptoms were well controlled by a combination therapy of prednisolone and lomustine (CCNU), and survived for two months after diagnosis. This case was definitively diagnosed as a nasal neuroendocrine carcinoma based on histopathological findings. This report describes the clinical findings, imaging characteristics, and pathologic features of secondary brain tumor which caused by infiltration of nasal neuroendocrine carcinoma in a dog.

• Journal of Korean Neurosurgical Society
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• v.56 no.5
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• pp.383-389
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• 2014

Objective : Neural tissue transplantation has been a promising strategy for the treatment of Parkinson's disease (PD). However, transplantation has the disadvantages of low-cell survival and/or development of dyskinesia. Transplantation of cell aggregates has the potential to overcome these problems, because the cells can extend their axons into the host brain and establish synaptic connections with host neurons. In this present study, aggregates of human brain-derived neural stem cells (HB-NSC) were transplanted into a PD animal model and compared to previous report on transplantation of single-cell suspensions. Methods : Rats received an injection of 6-OHDA into the right medial forebrain bundle to generate the PD model and followed by injections of PBS only, or HB-NSC aggregates in PBS into the ipsilateral striatum. Behavioral tests, multitracer (2-deoxy-2-[$^{18}F$]-fluoro-D-glucose ([$^{18}F$]-FDG) and [$^{18}F$]-N-(3-fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl)nortropane ([$^{18}F$]-FP-CIT) microPET scans, as well as immunohistochemical (IHC) and immunofluorescent (IF) staining were conducted to evaluate the results. Results : The stepping test showed significant improvement of contralateral forelimb control in the HB-NSC group from 6-10 weeks compared to the control group (p<0.05). [$^{18}F$]-FP-CIT microPET at 10 weeks posttransplantation demonstrated a significant increase in uptake in the HB-NSC group compared to pretransplantation (p<0.05). In IHC and IF staining, tyrosine hydroxylase and human ${\beta}2$ microglobulin (a human cell marker) positive cells were visualized at the transplant site. Conclusion : These results suggest that the HB-NSC aggregates can survive in the striatum and exert therapeutic effects in a PD model by secreting dopamine.

• The Journal of Korean Medicine
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• v.26 no.2 s.62
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• pp.217-230
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• 2005

Objectives: Chungpaesagan-tang (CPSGT), which is frequently used for treating patients of cerebrovascular disease, has not been reported by clinical doctors concerning the effect of neuronal aptosis caused by brain ischemia. To study the effect of CPSGT on focal cerebral ischemia in normal and diabetic rats and SHR, focal cerebral ischemia was induced by transient MCAO, and after onset CPSGT was administrated. Methods: Rats (Sprague-Dawley) were divided into four groups: sham-operated group, MCA-occluded group, CPSGT­administrated group after MCA occlusion, and normal group. The MCA was occluded by intraluminal method. CPSGT was administrated orally twice (l and 4 hours) after middle cerebral artery occlusion. All groups were sacrificed at 24 hours after the surgery. The brain tissue Was stained with $2\%$ triphenyl tetrazolium chloride (TTC) or $1\%$ cresyl violet solution, to examine effect of CPSGT on ischemic brain tissue. The blood samples were obtained from the heart.~. Tumor necrosis $factor-\alpha$ level and interleukin-6 level of serum was measured from sera using enzyme-linked immunoabsorbent assay (ELISA). Then changes of immunohistochemical expression of $TNF-\alpha$ in ischemic damaged areas were observed. Results: In NC+MCAO+CP and DM+MCAO+CP, CPSGT significantly (p<0.01) decreased the number of neuron cells compared to the control group. CPSGT markedly reduced (p<0.01) the infarct size of the forebrain in distance from the interaural line on cerebral ischemia in diabetic rats. CPSGT significantly reduced the $TNF-\alpha$ expression in penumbra region of damaged hemisphere in diabetic rats. Conclusions: CPSGT had a protective effect on cerebral ischemia in SD rats, especially in diabetic rats compared with normal SD rats.

• Development and Reproduction
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• v.15 no.2
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• pp.143-150
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• 2011

The objective of this study was to determine the effect of exercise on a hemiparkinsonian rat model. Nigrostriatal dopamine cell lesions were produced by injecting 6-hydroxydopamine at the left medial forebrain bundle of rats. In this study, the rats were divided into the following 4 groups: the control group without any exercise, experimental group I with aqua-exercise (Exp I), experimental group II with balance exercise (Exp II) and experimental group III with complex exercise (aqua-exercise+balance exercise; (Exp III)). Exercises were applied to all the experimental groups after the operation. In order to observe the dopaminergic cell loss, we assessed the level of tyrosine hydroxylase (TH) expression in the midbrain of rats, and performed the apomorphine-induced rotation test at postoperative days (PDs) 7, 14, and 21. Experimental groups had significantly higher TH-immunoreactivity and behavioral performance than the control group. However, there was no difference in TH-immunoreactivity and behavioral performance across the experimental groups. These results suggest that the application of aqua-exercise and balance exercise could suppress dopaminergic cell loss in the substantia nigra of rat brains and could increase behavioral recovery in hemiparkinsonian rats.

• Korean Journal of Veterinary Research
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• v.55 no.2
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• pp.133-139
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• 2015

The increasing uses of zinc oxide nanoparticles (nZnO) in industrial and personal care products raise possible danger of using nZnO in human. To determine whether ZnO induces size-dependent anomalies during embryonic organogenesis, mouse embryos on embryonic day 8.5 were cultured for 2 days under 50, 100, and $150{\mu}g$ of nZnO (< 100 nm) or micro-sized ZnO (mZnO; $80{\pm}25{\mu}m$), after which the morphological changes, cumulative quantity of Zn particles, and expressions of antioxidant and apoptotic genes were investigated. Although embryos exposed to $50{\mu}g$ of ZnO exhibited no defects on organogenesis, embryos exposed to over $100{\mu}g$ of ZnO showed increasing anomalies. Embryos treated with $150{\mu}g$ of nZnO revealed significant changes in Zn absorption level and morphological parameters including yolk sac diameter, head length, flexion, hindbrain, forebrain, branchial bars, maxillary process, mandibular process, forelimb, and total score compared to the same dose of mZnO-treated embryos. Furthermore, CuZn-superoxide dismutase, cytoplasmic glutathione peroxidase (GPx) and phospholipid hydroperoxidase GPx mRNA levels were significantly decreased, but caspase-3 mRNA level was greatly increased in nZnO-treated embryos as compared to normal control embryos. These findings indicate that nZnO has severer teratogenic effects than mZnO in developing embryos.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.4
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• pp.595-599
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• 2013

Alzheimer's disease is a progressive neurodegenerative disorder characterized by a gradual decline in memory associated with shrinkage of brain tissue, with a localized loss of neurons mainly in the hippocampus and basal forebrain. This study investigated the neuroprotective effect of Gastrodia elata aqueous extracts against scopolamine-induced neurotoxicity in the hippocampus of male Sprague-Dawley rats. The animals (n=25) were divided into five different groups with five animals per each group. The normal group (Nor) was administered with saline, while the control (Con) group was administered saline after scopolamine treatment. The experimental group (Exp) was administered Gastrodia elata aqueous extracts (200 mg/kg body weight) for 20 or 30 days after scopolamine treatment. From a light microscopy study, the nuclei of neurons in the hippocampus were more shrunken or condensed in the 20 or 30 day control groups compared to experimental groups. The densities of neurons from the CA1 and CA3 area of the hippocampus in the Exp increased compared with the Con. Amyloid ${\beta}$ protein, containing PAS-positive materials, was lower in the Exp compared with the Con. The present study demonstrates that Gastrodia elata aqueous extracts possess neuroprotective potential, thus validating its use in alleviating the toxic effects of scopolamine.

• The Journal of Korean Medicine
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• v.23 no.4
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• pp.161-168
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• 2002

Objectives: Hwangryunhaedok-tang (Huang-lian-jie-du-tang, HRHDT, 黃連解毒湯) is a traditional Korean herbal medicine that is formulated with Coptidis Rhizoma, Phellodendri Cortex, Scutellariae Radix and Gardeniae Fructus. HRHDT is cold (寒) and bitter (苦) in nature and has general properties of clearing heat and detoxifying (淸熱解毒), strengthening the stomach and settling the liver (健胃平肝), and reducing inflammation, fever and swelling. This formula can prevent and treat artherosclerosis, hyperplasia of the endothelium, cerebral fluid circulation, cerebral vascular deterioration through aging, impairment of neurotransmitters, or disruption of the functioning of the cerebral cortex following infection or trauma. The purpose of the study reported here was to determine the neuroprotective effect of HRHDT on global ischemia induced by 4-vessel occlusion in Wistar rats. Methods: HRHDT extract was lyophilized after extraction with 85% methanol and 100% water. Rats were induced to 10 minutes of forebrain ischemia by 4-vessel occlusion (4-VO) and reperfused again. HRHDT was administered with a dose of 100 mg/kg, and 500 mg/kg of 85% methanol extracts and 100 mg/kg of 100% water extracts, respectively, at 0 min and 90 min after 4-VO. Rats were killed at 7 days after ischemia and the number of CA1 pyramidal neurons was counted in hippocampal sections stained with cresyl violet. Results: Body temperature of animals showed no significant difference between saline-treated groups and HRHDT extracts-treated groups until 5 hours of reperfusion. This result indicated that neuroprotective effects of HRHDT extracts were not due to hypothermic effects. The administration of HRHDT showed a significant neuroprotective effect on hippocampal CA1 neurons at 7 days after ischemia compared to the saline-treated group (P<0.001). HRHDT methanol extracts of 100 mg/kg, 500 mg/kg and HRHDT water extracts of 100 mg/kg showed 88.5%, 98.3% and 95.1 % neuroprotection, respectively. Conclusions: The results of this study demonstrate that administration of HRHDT is highly effective in reducing neuronal damage in response to transient global cerebral ischemia. HRHDT may involve many mechanisms that might account for its high degree of efficacy. A number of factors including free radicals, glutamate, calcium overload, NO, and various cytokines have been proposed to have an important role in causing neuronal death after short periods of global ischemia. Further studies are needed to know the neuroprotective mechanisms of HRHDT.

• Molecules and Cells
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• v.20 no.3
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• pp.401-408
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• 2005

Reactive oxygen species (ROS) contribute to the development of various human diseases. Cu,Zn-superoxide dismutase (SOD) is one of the major means by which cells counteract the deleterious effects of ROS. SOD activity is dependent upon bound copper ions supplied by its partner metallochaperone protein, copper chaperone for SOD (CCS). In the present study, we investigated the protective effects of PEP-1-CCS against neuronal cell death and ischemic insults. When PEP-1-CCS was added to the culture medium of neuronal cells, it rapidly entered the cells and protected them against paraquat-induced cell death. Moreover, transduced PEP-1-CCS markedly increased endogenous SOD activity in the cells. Immunohistochemical analysis revealed that it prevented neuronal cell death in the hippocampus in response to transient forebrain ischemia. These results suggest that CCS is essential to activate SOD, and that transduction of PEP-1-CCS provides a potential strategy for therapeutic delivery in various human diseases including stroke related to SOD or ROS.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.40
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• pp.40.1-40.8
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• 2018

Background: A 9-year-old male showed severe defects in midface structures, which resulted in maxillary hypoplasia, ocular hypertelorism, relative mandibular prognathism, and syndactyly. He had been diagnosed as having Apert syndrome and received a surgery of frontal calvaria distraction osteotomy to treat the steep forehead at 6 months old, and a surgery of digital separation to treat severe syndactyly of both hands at 6 years old. Nevertheless, he still showed a turribrachycephalic cranial profile with proptosis, a horizontal groove above supraorbital ridge, and a short nose with bulbous tip. Methods: Fundamental aberrant growth may be associated with the cranial base structure in radiological observation. Results: The Apert syndrome patient had a shorter and thinner nasal septum in panthomogram, PA view, and Waters' view; shorter zygomatico-maxillary width (83.5 mm) in Waters' view; shorter length between the sella and nasion (63.7 mm) on cephalogram; and bigger zygomatic axis angle of the cranial base (118.2°) in basal cranial view than a normal 9-year-old male (94.8 mm, 72.5 mm, 98.1°, respectively). On the other hand, the Apert syndrome patient showed interdigitating calcification of coronal suture similar to that of a normal 30-year-old male in a skull PA view. Conclusion: Taken together, the Apert syndrome patient, 9 years old, showed retarded growth of the anterior cranial base affecting severe midface hypoplasia, which resulted in a hypoplastic nasal septum axis, retruded zygomatic axes, and retarded growth of the maxilla and palate even after frontal calvaria distraction osteotomy 8 years ago. Therefore, it was suggested that the severe midface hypoplasia and dysostotic facial profile of the present Apert syndrome case are closely relevant to the aberrant growth of the anterior cranial base supporting the whole oro-facial and forebrain development.