• Journal of Ginseng Research
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• v.37 no.4
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• pp.401-412
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• 2013

Korean Red Ginseng (KRG) is an oriental herbal preparation obtained from Panax ginseng Meyer (Araliaceae). To expand our understanding of the action of KRG on central nervous system (CNS) function, we examined the effects of KRG on tissue plasminogen activator (tPA)/plasminogen activator inhibitor-1 (PAI-1) expression in rat primary astrocytes. KRG extract was treated in cultured rat primary astrocytes and neuron in a concentration range of 0.1 to 1.0 mg/mL and the expression of functional tPA/PAI-1 was examined by casein zymography, Western blot and reverse transcription-polymerase chain reaction. KRG extracts increased PAI-1 expression in rat primary astrocytes in a concentration dependent manner (0.1 to 1.0 mg/mL) without affecting the expression of tPA itself. Treatment of 1.0 mg/mL KRG increased PAI-1 protein expression in rat primary astrocytes to $319.3{\pm}65.9%$ as compared with control. The increased PAI-1 expression mediated the overall decrease in tPA activity in rat primary astrocytes. Due to the lack of PAI-1 expression in neuron, KRG did not affect tPA activity in neuron. KRG treatment induced a concentration dependent activation of PI3K, p38, ERK1/2, and JNK in rat primary astrocytes and treatment of PI3K or MAPK inhibitors such as LY294002, U0126, SB203580, and SP600125 (10 ${\mu}M$ each), significantly inhibited 1.0 mg/mL KRG-induced expression of PAI-1 and down-regulation of tPA activity in rat primary astrocytes. Furthermore, compound K but not other ginsenosides such as Rb1 and Rg1 induced PAI-1 expression. KRG-induced up-regulation of PAI-1 in astrocytes may play important role in the regulation of overall tPA activity in brain, which might underlie some of the beneficial effects of KRG on CNS such as neuroprotection in ischemia and brain damaging condition as well as prevention or recovery from addiction.

• Journal of Chest Surgery
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• v.30 no.8
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• pp.752-759
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• 1997

Profound hypothermia protects . cerebral function during total circulatory arrest(TCA) in the surgical treatment of a variety of cardiac and aortic diseases. Despite its importance, there is no ideal technique to monitor the brain injury from ischemia. Since 1994, we have developed compressed spectral array(CSA) of electroencephalography(EEG) and monitored cerebral activity to reduce ischemic injury. The purposes of this study are to analyse the efficacy of CSA and to establish objective criteria to consistently identify the safe level of temperature and arrest time. We studied 6 patients with aortic dissection(AD, n=3) or aortic arch aneurysm(n=3, ruptured in 2). Body temperatures from rectum and esophagus and the EEG were monitored continuously during cooling and rewarming period. TCA with cerebral ischemia was performed in 3 patients and TCA with selective cerebral perfusion was performed in 3 patients. Total ischemic time was 30, 36 and 56 minutes respectively for TCA group and selective perfusion time was 41, 56 and 92 minutes respectively for selective perfusion group. The rectal temperatures for flat EEG were between 16.1 and 22. $1^{\circ}C$ (mean: 18.4 $\pm$ 2.0): the esophageal temperatures between 12.7 and $16.4^{\circ}C$ (mean $14.7\pm1.6).$ The temperatures at which EEG reappeared $5~15.4^{\circ}C$ for esophagus. There was no neurological defic t and no surgical mortality in this series. In summary, the electrical cerebral activity Teappeared within 23 minutes at the temperature less than $16^{\circ}C$ for rectum. It seemed that $15^{\circ}C$ of esophageal temperature was not safe for 20 minutes of TCA and continuous monitoring the EEG with CSA to identify the electrocerebral silence was useful.

• The Korean Journal of Nuclear Medicine
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• v.30 no.4
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• pp.484-492
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• 1996

To detect ischemic tissue in experimental model of cerebral ischemia made by middle cerebral artery(MCA)-occlusion, we acquired triple image of $^{99m}Tc$-glucarate, [$^{18}F$]fluoro-deoxyglucose (FDG), and 2,3,5- triphenyltetrazolium (TTC) staining. We made cerebral infarction either with reperfusion (after occlusion of 2 hours) or without reperfusion in 10 Sprague-Dawley rats by inserting thread to MCA through internal carotid artery. After 22 hours, we injected 740 MBq of $^{99m}Tc$-glucarate and 55.5 MBq of [$^{18}F$]FDG through tail vein. Each 1 mm slice of rat brains was frozen and exposed to imaging plate for 20 minutes in freezer to get an [$^{18}F$]FDG image. After 20 hours enough to fade radioactivity of [$^{18}F$]FDG, the slices were again imaged by BAS1500 for $^{99m}Tc$-glucarate uptake. Finally, these brain tissues were stained with TTC. Semi-quantitative visual analysis was done by grading 0 to 3 points according to the degree of uptakes($^{99m}Tc$-glucarate) and decreased uptakes([$^{18}F$]FDG and TTC). Ten rats survived with neurologic symptoms. TTC staining confirmed the development of infarction. The size of the infarction was relatively larger in the group without reperfusion. [$^{18}F$]FDG images were similar to TTC-stained images. However, we found regions with intermediate uptake which were not stained with TTC. We found regions with intermediate [$^{18}F$]FDG uptake where TTC staining was normal. $^{99m}Tc$-glucarate uptake was round only in TTC non-stained region. In the TTC stained regions, there were no uptake of $^{99m}Tc$-glucarate. We could not find clear relation between $^{99m}Tc$-glucarate uptake with [$^{18}F$]FDG uptake. This was partly because percent uptake of $^{99m}Tc$-glucarate was so small (less than 1 percent of injected dose) and because there were quite heterogeneity of patterns of [$^{18}F$]FDG uptake and TTC. With these findings, we could conclude that $^{99m}Tc$-glucarate were taken up only in part of ischemic tissues which were proven to be nonviable. The establishment of MCA-occluded rat model with or without reperfusion and triple imaging for $^{99m}Tc,\;^{18}F$ and TTC helped the characterization of $^{99m}Tc$-glucarate uptakes. Further work is needed to clarify the meaning or diversities or [$^{18}F$]FDG and TTC and their relation with $^{99m}Tc$-glucarate.

• Neonatal Medicine
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• v.18 no.1
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• pp.59-69
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• 2011

Purpose: Current studies have demonstrated the neuroprotective effects of 6-cyano-7-nitroquinoxalin-2,3-dione (CNQX) in many animal models of brain injury, including hypoxic-ischemic (HI) encephlopathy, trauma and excitotoxicity, but limited data are available for those during the neonatal periods. Here we investigated whether CNQX can protect the developing rat brain from HI injury via mediation of nitric oxide synthase. Methods: In an in vivo model, left carotid artery ligation was done in 7-day-old Sprague-Dawley (SD) rat pups. The animals were divided into six groups; normoxia (N), hypoxia (H), hypoxia with sham-operation (HS), hypoxia with operation (HO), HO treated with vehicle (HV), and HO treated with CNQX at a dose of 10 mg/kg (HC). Hypoxia was made by exposure to a 2 hr period in the hypoxic chamber (92% $N_2$, 8% $O_2$). In an in vitro model, embryonic cortical neuronal cell culture of SD rats at 18-day gestation was done. The cultured cells were divided into three groups: normoxia (N), hypoxia (H), and hypoxia treated with CNQX (HC). The N group was prepared in 5% $CO_2$ incubators and the other groups were placed in 1% $O_2$) incubators (94% $N_2$, 5% $CO_2$) for 16 hr. Results: In the in vitvo and in vivo models, the expressions of iNOS and eNOS were reduced in the hypoxia group when compared to the normoxia group, whereas they were increased in the CNQX-treated group compared to the hypoxia group. In contrast, the expression of nNOS was showed reversely. Conclusion: CNQX has neuroprotective property over perinatal HI brain injury via mediation of nitric oxide synthase.

• Clinical and Experimental Pediatrics
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• v.51 no.11
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• pp.1205-1210
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• 2008

Purpose : The development of the corpus callosum occupies the entire period of cerebral formation. The myelination pattern on magnetic resonance imaging (MRI) is very useful to evaluate neurologic development and to predict neurologic outcome in high risk infants. The thickness of the corpus callosum is believed to depend on the myelination process. It is possible to calculate the length and thickness of the corpus callosum on MRI. Thus, we can quantitatively evaluate the development of the corpus callosum. We investigated the clinical significance of measuring various portions of the corpus callosum in neonate with neurologic disorders such as hypoxic brain damage and seizure disorder. Methods : Forty-two neonates were evaluated by brain MRI. We measured the size of the genu, body, transitional zone, splenium, and length of the corpus callosum. Each measurement was divided by the total length of the corpus callosum to obtain its corrected size. The ratio of corpus callosal length and the anteroposterior diameter of the brain was also measured. Results : There was no statistical significance in the sample size of each part of the corpus callosum. However, the corrected size or the ratio of body of the corpus callosum correlated with periventricular leukomalacia and hypoxic ischemic encephalopathy. Conclusion : The abnormal size of the corpus callosum showed a good correlation with periventricular leukomalacia and hypoxic ischemic encephalopathy in neonates. We can predict clinical neurological problems by estimation of the corpus callosum in the neonatal period.

• The Korean Journal of Nuclear Medicine
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• v.33 no.4
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• pp.352-361
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• 1999

Purpose: Carotid endarterectomy nay benefit patients with bilateral carotid stenosis by improving cerebro-vascular hemodynamics of ipsilateral as well as contralateral cerebral hemispheres. We investigated cerebro-vascular hemodynamics after carotid endarterectomy in patients with contralateral carotid occlusion by acetazolamide stress brain SPECT. Materials and Methods: Subjects were 14 symptomatic patients (all men, mean age 66 yrs) with carotid stenosis (>50%) with contralateral carotid occlusion. Acetazolamide stress Tc-99m ECD brain SPECTs were performed within 2 weeks before and after carotid endarterectomy using one day protocol. Cerebral blood flow (CBF) and cerebrovascular reserve (CVR) were assessed visually. In 12 patients, correlation between the patency of proximal anterior cerebral or anterior communicating arteries (A1/A-comm) and the improvement of CBF or CVR after endarterectomy was assessed. Results: Preoperative SPECT showed reduced CBF in 2 ipsilateral and 10 contralateral hemispheres. CVR was reduced in 4 ipsilateral and 9 contralateral hemispheres. Of 12 hemispheres with reduced CBF, 2 hemispheres (16.7%) showed improvement of CBF after endarterectomy. However, reduced CVR was improved in all 4 ipsilateral and 7 of 9 (78%) of contralateral hemispheres after endarterectomy. Three of4 with stenotic Al/A-comm and 4 of 8 with patent A1/A-comm had reduced contralateral CVR. Reduced contralateral CVR improved in all 3 patients with stenotic A1/A-comm and 3 of 4 with patent A1/A-comm. Conclusion: Acetazolamide stress brain SPECT demonstrated improvement of compromised cerebrovascular reserve in not only ipsilateral but also contralateral hemispheres of patients with contralateral carotid occlusion after carotid endarterectomy, and may, therefore, be useful for evaluating cerebral blood flow and cerebrovascular reserve after carotid endarterectomy.

• Clinical and Experimental Pediatrics
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• v.46 no.10
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• pp.966-971
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• 2003

Purpose : It is now well established that infection and inflammation play an important role in the pathogenesis of ischemic brain damage. The loss of neutrophils from systemic circulation is an associated finding in injury mediated by granulocyte. Periventricular leukomalacia(PVL) caused by ischemia is the principal form of brain injury in premature infants. This study was conducted to evaluate whether the low neutrophil count is associated with periventricular leukomalacia(PVL) in premature infants. Methods : Retrospective review of medical records was undertaken. Subjects were premature infants with a birth weight of less than 1,500 gm, admitted to the Neonatal Intensive Care Unit of Kyungpook University Hospital. A complete blood count of peripheral blood was done within the 1st hour of life. Neutropenia was defined as absolute neutrophil count < $1,500/mm^3$, PVL as increased periventricular echodensities followed by cyst formation on ultrasonography or corresponding signs on brain MRI. Results : Thirteen infants out of a total population of 37 revealed neutropenia. Respiratory distress syndrome and requirement for respiratory support were not different between infants with neutropenia( neutropenia group) and infants without neutropenia(control group). Intraventricular hemorrhage (IVH) and grade 3 and 4 IVH were more frequent in neutropenia group(P<0.05). There was no statistically significant increase of PVL in neutropenia group. The neutrophil count was $18,760.0{\pm}10,266.1/mm^3$, $7,272.0{\pm}7,435.0/mm^3$ infants with PVL and $11,131.7{\pm}3,386.5/mm^3$, $2,407.5{\pm}1,933.1/mm^3$ in infants without PVL, respectively. The frequency of mechanical ventilation and artificial surfactant therapy was higher in infants with PVL compared with infants without PVL, but statistical analysis was not performed due to small number of subjects. Conclusion : A low number of neutrophils in the systemic circulation was not associated with an increased risk of PVL in premature infants.

• The Korean Journal of Pharmacology
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• v.32 no.3
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• pp.323-334
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• 1996

Male Mongolian gerbils $(60{\sim}80g)$ were given DL-difluoromethylornithine (DFMO; 250mg/kg, ip) and methylglyoxal bis(guanylhydrazone) (MGBG; 50 mg/k, ip), respectively, 1 h prior to transient (7 min) occlusion of bilateral common carotid arteries (OBC7) and a daily dose of one of them for 6 days after recirculation, and the polyamine contents, activities of ornithine and S-adenosylmethionine decarboxylases (ODC and SAM-DC), and light microscopic findings of the hippocampus were evaluated. The hippocampal putrescine (PT) levels of the control gerbils treated with saline (STGr), markedly increased after OBC7, showing a peak level at 24 h after recirculation. The peak PT level was reduced in DFMO treated gerbils (DTCr) and in MGBG treated gerbils (MTGr). And 7 days after recirculation, the PT level of DTGr was decreased to about 75% of the PT level in the sham operated group (nonTGr) and to about 55% of the STGr level, respectively. The hippocampal spermidine (SD) level of STGr tended to decline, showing the lowest value at 8 h after recirculation. But the spermidine (SD) level of DTGr was somewhat higher at 8 h after OBC7 than those of STGr and MTGr The hippocampal spermine (SM) levels of all the experimental groups were little changed for 7 days after OBC. OBC7 markedly increased the hippocampal ODC activity. reaching a maximum (about 3 times higher than preischemic level) at 8 h and rapidly recovered to the control value by 24 h in STGr gerbils, and the OBC7-induced increase of ODC activity was significantly attenuated by DFMO or MGBG treatment. Whereas OBC7 induced a rapid decrease of the hippocampal SAMDC activity follwed by gradual recovery to the preischemic level, and the decrease of the SAMDC activity was slightly attenuated by DFMO or MGBG treatment. 7 Days after OBC7 the histological finding of the hippocampal complex stained with cresyl violet showed an extensive delayed neuronal damage in the CA1 region and to a lesser extent, in the dentate gyrus, sparing the CA3 region. And the neuronal death was aggevated by DFMO but significantly attenuated by MGBG. The immunochemical reactivity of hippocampus to anti-GFAP antibody was significantly increased in the CA1 region and to a lesser extent, in the dentate gyrus 7 days after OBC7, but was little changed in the CA3. And the increase of the anti-GFAP immunoreactivity was moderately enhanced by DFMO and significantly suppressed by MGBG. These results suggest that the polyamine metabolism may play a modulatory role in the ischemic brain damage.

• Investigative Magnetic Resonance Imaging
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• v.3 no.2
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• pp.173-178
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• 1999

Purpose : To evaluate the usefulness of functional MRI (fMRI) of visual cortex in patients with ischemic infarction in the occipital lobe. Materials and Methods : Four patients with the symptoms and signs of visual cortical ischemia were included. Functional MRI was performed by 2D-FLASH technique with the parameter of 90/56msec TR/TE, $40^{\circ}$ flip angle, $240{\times}240{\;}FOV,{\;}64{\times}128$ matrix number, 8.32 seconds acquisition time, 8mm slice thickness. An axial slice including both visual cortices was selected and alternative activation and resting of the visual cortex was performed using red color photostimulator. all patients undertook visual field test, and vascular abnormality was examined by MRA (n=4) and DSA (n=2). fMRI results were compared with the results of a visual field test, conventional MRI and cerebral angiography. Results : On fMRI, decreased activity of the visual cortex was found in the occipital lobe corresponding to stenosis of the posterior cerebral artery or its branch noted on angiogram. However, 2 of 4 patients showed no abnormal findings on conventional MRI. Visual field defect was noted in 3 patients, one and of whom showed no abnormality on conventional MRI and diffusion-weighted image, but revealed decreased activity in the corresponding visual cortex on fMRI. Conclusion : fMRI may be a sensitive method for detection of the status of decreased blood flow or vascular reserve which other methods can not.

• Journal of Chest Surgery
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• v.34 no.11
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• pp.823-830
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• 2001

Background: Paraplegia is a serious complication of thoracic or thoracoabdominal aortic operations, which is related to ischemic injury of the spinal cord induced by low perfusion pressure during cross clamping of the aorta. Ischemic preconditioning of heart or brain with reversible sublethal ischemic injury induces resistance to subsequent lethal ischemia. The aim of this study is to investigate whether ischemic tolerance could be induced by the preconditioning of the spinal cord using swine model. Material and Method: The animals were randomly assigned to three groups: sham group(n=3), control group(n=6) and pre-conditioning group(n=8). In the sham group, we performed the left thoracotomy only without any ischemic injury. In the preconditioning group, the swine received reversible spinal cord ischemic injury by aortic clamping for 20 minutes, whereas control group had no previous aortic cross- clamping. Forty-eight hours later, the aorta was clamped for 30 minutes in both groups. Neurological examination was done 24 hours later, then the animals were euthanized for histopathology and malonedialdehyde(MDA) spectrophotometry assay of the spinal cord. Result: Statistically significant difference in neurological outcome was observed between the control and preconditioning groups at 24 hours after ischemic injury. The incidence of paraplegia and severe paresis was 100% in the control group, and 62.5% in the preconditing group(p=0.028). There was no statistically significant difference in histopathology and MDA assay of the ischemic spinal cord between these two groups with borderline statistical difference in MDA assay(p=0.0745). Conclusion: In the present swine study, ischemic preconditioning could induce tolerance against 30 minute ischemic insult of the spinal cord, although the animals did not completely recover(stand-up or walk). We expect that combining this preconditioning with other currently existing protection methods might lead to a synergistic effect, which warrants further investigation.