• Clinical and Experimental Pediatrics
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• v.52 no.12
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• pp.1337-1347
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• 2009

Purpose:Taurine (2-aminoethanesulfonic acid) is a simple sulfur-containing amino acid. It is abundantly present in tissues such as brain, retina, heart, and skeletal muscles. Current studies have demonstrated the neuroprotective effects of taurine, but limited data are available for such effects during neonatal period. The aim of this study was to determine whether taurine could reduce hypoxic-ischemic (HI) cerebral injury via anti-apoptosis mechanism. Methods:Embryonic cortical neurons isolated from Sprague-Dawley (SD) rats at 18 days gestation were cultured in vitro. The cells were divided into hypoxia group, taurine-treated group before hypoxic insult, and taurine-treated group after HI insult. In the in vivo model, left carotid artery ligation was performed in 7-day-old SD rat pups. The pups were exposed to hypoxia, administered an injection of 30 mg/kg of taurine, and killed at 1 day, 3 days, 1 week, 2 weeks, and 4 weeks after the hypoxic insult. We compared the expressions of Bcl-2, Bax, and caspase-3 among the 3 groups by using real- time polymerase chain reaction (PCR) and western blotting. Results:The cells in the taurine-treated group before hypoxic insult, although similar in appearance to those in the normoxia group, were lesser in number. In the taurine-treated group, Bcl-2 expression increased, whereas Bax and caspase-3 expressions reduced. Conclusion:Taurine exerts neuroprotective effects onperinatal HI brain injury due to its anti-apoptotic effect. The neuroprotective effect was maximal at 1-2 weeks after the hypoxic injury.

• 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.

• Investigative Magnetic Resonance Imaging
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• v.8 no.1
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• pp.17-23
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• 2004

Purpose : To evaluate changes in total cerebral blood flow (tCBF) with aging, parenchymal volume changes and vascular abnormalities, using 2 dimensional (D) phase-contrast magnetic resonance imaging (PC MRI). Materials and Methods : Routine brain MRI including T2 weighted image, time-of-flight (TOF) MR Angiography (MRA) and 2D PC MRI were performed in 73 individuals, including 12 volunteers. Normal subjects (12 volunteers, and 21 individuals with normal MRI and normal MRA) were classified into groups according to age (18-29, 30-49 and 50-66 years). For the group with abnormalities in brain MRIs, cerebral parenchymal volume changes were scored according to the T2 weighted images, and atherosclerotic changes were scored according to the MRA findings. Abnormal groups were classified into 4 groups: (i) mild reduction in volume, (ii) marked reduction in volume by parenchymal volume and atherosclerotic changes, and (iii) increased volume and (iv) Moya-moya disease. Volumetric flow was measured at the internal carotid artery (ICA) and vertebral artery bilaterally using the velocity-flow diagrams from PC MRI, and combined 4 vessel flows and tCBF were compared among all the groups. Results : The age-specific distribution of tCBFs in normal subjects were as follows: $12.0{\pm}2.1ml/sec$ in 18-29 years group, $11.8{\pm}1.9ml/sec$ in 30-49 years group, $10.9{\pm}2.2ml/sec$ in 50-66 years group. The distribution of tCBFs in the different subsets of the abnormal population were as follows: $9.5{\pm}2.5ml/sec$ in the group with mild reduction in volume, $7.6{\pm}2.0ml/sec$ in the group with marked reduction in volume, and $7.3{\pm}1.2ml/sec$ and $7.0{\pm}1.1ml/sec$ in the increased parenchymal volume and Moya-moya disease groups respectively. Conclusion : Total cerebral blood flow decreases with increasing age with a concomitant reduction in parenchymal volumes and increasing atherosclerotic changes. It is also reduced in the presence of increased parenchymal volume and Moya-moya disease.2D PC MRI can be used as a tool to evaluate tCBF with aging and in the presence of various conditions that can affect parenchymal volume and cerebral vasculature.

• The Korean Journal of Pharmacology
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• v.32 no.3
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• pp.335-345
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• 1996

A critical role of oxygen-derived free radicals has been implicated in ischemia/reperfusion (I/R)-induced brain damage. In this study, we have produced experimental I/R to the brains of Mongolian gerbil (Meriones unguiculatus) by a transient occlusion and release of the common carotid arteries. We have attempted to determine whether the oxidative stress is generated upon I/R and whether this oxidative stress is linked to the cell damage. Since hippocampus has been suggested as one of the most vulnerable regions of the brain to the oxidative stress, we analyzed samples from hippocampus in comparison with those from cortex. In addition, we have examined the expression of heat shock protein 70kD species (HSP70) in these regions in order to evaluate a possible role of this protein in I/R-induced brain damage. To determine whether the oxidative stress is produced upon I/R, we measured the glutathione oxidation, GSSG/ (GSH + 2xGSSG), as an index of oxidative stress. We found an increase of the glutathione oxidation primarily in hippocampus upon I/R. To determine whether this oxidative stress is linked to the cell damage, we measured the degree of lipid peroxidation upon I/R. We found an increase of lipid peroxidation in both regions. However, the magnitude of increases was greater in hippocampus than in cortex. In addition, we found that changes in both the magnitude and the temporal patterns of glutathione oxidation closely correlated with those of lipid peroxidation. Our study provides biochemical evidences that the oxidative stress is generated upon I/R and this oxidative stress is linked to the oxidative cell damage. Our study also provides evidences that the degree of oxidative stress as well as oxidative cell damage is greater in hippocampus than in cortex. We could not find difference in the basal level of HSP70 expression between hippocampus and cortex, indicating that the intrinsic vulnerability of hippocampus cannot be explained by the lower level of HSP70 expression. We did find, however, that the induction of HSP70 expression upon I/R was impaired in the hippocampus. This impairment appeared to be at the transcriptional level. These results suggest that the measurement of HSP70 induction may be employed as a useful predictor of differential cellular susceptibilities to the I/R-induced brain damage.

• Clinical and Experimental Pediatrics
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• v.45 no.6
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• pp.732-742
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• 2002

Purpose : In order to evaluate the hypoxia-ischemia(H-I) induced neurotoxicity and the protective effect of xanthine oxidase(XO) inhibitor(allopurinol), cell number, cell viability, lactate dehydrogenase(LDH), protein synthesis(PS) and protein kinase C(PKC) activity were measured in cerebral neurons and astrocytes. Methods : Cytotoxic effect was measured by in vitro assay at 12-72 hours after H-I on cerebral neurons and astrocytes derived from 7-day old neonatal rats which were subjected to unilateral common carotid artery occlusion and exposed to hypoxic condition for 3 hours. The protective effect of XO inhibitor was examined by the cell number, cell viability, LDH and PS on 14 days after H-I with allopurinol intraperitoneal injection 15 minutes prior to H-I. In addition, the effect of allopurinol on PKC activity in hypoxic conditions was examined in neurons. Results : 72 hours from H-I, the cell numbers and viability were decreased significantly in time-dependent manner on neurons and those of astrocytes also decreased slightly, compared with control. In neonatal rats treated with H-I, the cell number, cell viability, and PS in neurons were decreased, but LDH was increased significantly compared with control. In neonatal rats pretreated with allopurinol, the cell number and viability, and PS in neurons were increased and LDH was decreased significantly compared with H-I. PKC was increased remarkably after hypoxic condition. But PKC was decreased significantly against hypoxic condition after allopurinol pretreatment. Conclusion : From these results, it is suggested that H-I is more toxic in neurons than astrocytes and allopurinol is very protective with increasing of PS, and decreasing of LDH and PKC in neurons from hypoxic-ischemic condition.

• Clinical and Experimental Pediatrics
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• v.46 no.8
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• pp.789-794
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• 2003

Purpose : We intended to evaluate the effect of hypoxia-ischemia on extracellular striatal monoamine metabolism in neonatal rat brains by in vivo microdialysis. Methods : The right common carotid arteries of five or six-day old rats were surgically ligated, and the probes for microdialysis were inserted into the right striatum with stereotaxic instrument. After stabilization for two hours, artificial cerebrospinal fluid was infused via the probe for microdialysis and samples were collected during hypoxia-ischemia and recovery periods at 20 minute intervals. The concentrations of DA(dopamine), DOPAC(3,4-di-hydroxyphenyl acetic acid), HVA(homovanillic acid), NE(norepinephrine), and 5-HIAA(5-hydroxy indole-acetic acid) were measured by HPLC(high performance liquid chromatography) and the changes were analysed. Results : The striatal levels of dopamine metabolites such as DOPAC and HVA, were significantly decreased during hypoxia-ischemia, and increased to their basal level during reoxygenation(P<0.05). Dopamine mostly increased during hypoxia but statistically not significant(P>0.05). DOPAC showed the most remarkable decrease($23.0{\pm}4.2%$, P<0.05), during hypoxia-ischemia and increase to the basal levels during reoxygenation($120.8{\pm}54.9%$, P<0.05), and HVA showed the same pattern of changes as those of DOPAC during hypoxia-ischemia($35.3{\pm}7.6%$ of basal level, P<0.05) and reoxygenation ($105.8{\pm}32.3%$). However, the level of NE did not show significant changes during hypoxia-ischemia and reoxygenation. The levels of 5-HIAA decreased($74.9{\pm}3.1%$) and increased($118.1{\pm}7.8%$) during hypoxia-ischemia and reoxygenation, respectively(P<0.005). Conclusion : Hypoxia-ischemia had a significant influence on the metabolism of striatal monoamine in neonatal rat brains. These findings suggest that monoamine, especially dopamine, and its metabolites could have a significant role in the pathogenesis of hypoxic-ischemic injury of neonatal rat brains.

• Clinical and Experimental Pediatrics
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• v.49 no.4
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• pp.368-374
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• 2006

Purpose : The prevalence of obesity in children is increasing rapidly. Epidemiologic studies suggest that obesity induced atherosclerosis may start in childhood. We investigated whether obese children show early abnormalities of the arterial wall and endothelial dysfunction. Methods : Thirty-eight obese children(14-16 years old of age, male, body mass index $29.40{\pm}3.18kg/m^2$) and forty-five age and sex-matched healthy control children(body mass index $18.43{\pm}1.01kg/m^2$) were enrolled. Their carotid artery intima-media thickness(IMT) and brachial artery flowmediated dilation(FMD) response were measured by high-quality ultrasound system, and compliance, distensibility, stiffness index, incremental elastic modulus and wall stress were calculated by equation. In addition, we looked at the relations between these arterial features and metabolic cardiovascular risk factors. Results : The obese children had significantly increased IMT($0.52{\pm}0.09mm$ vs $0.40{\pm}0.07mm$, P< 0.001) and markedly impaired FMD($7.35{\pm}7.78$ percent vs $20.34{\pm}16.81$ percent, P<0.001) than the healthy controls. But the compliance and distensibility were lower, and the stiffness index, incremental elastic modules and wall stress were higher in the obese group than the control group, but not statistically significantly. Body mass index was highly associated with increased IMT(r=0.612, P<0.001) and reduced FMD(r=-0.414, P<0.001). Conclusion : We showed the deleterious effect of child obesity on both early functional and structural atherosclerotic markers. The ultrasonic findings will be used for screening and follow up markers to identify high-risk patients among obese children.

• Journal of radiological science and technology
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• v.32 no.1
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• pp.87-93
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• 2009

Background/aim : Atherosclerotic disease at the origin of the vertebral arteries is one of the risk factors for vertebrobasilar ischemic disease. Assessment and visualization of the origin of the vertebral arteries with color doppler sonography is a non-trivial task. The aim of this study is to increase the visualization rate of the origin of the vertebral arteries with color doppler sonography. Materials and Methods : Color doppler sonography for the vertebral arteries included carotid arteries was performed to 198 patients. We first examined the vertebral artery in the upper neck in the direction of the subclavian artery to distinguish its origin more easily. If the vertebral artery origin was not visualized in natural position, the examiner pushed the transducer toward a clavicle or pushed the shoulder of patient by the other hand. The technical methods for visualization of the vertebral artery origin were classified into three grades: natural position, pushing the transducer, and pushing the shoulder of patient according to the depth (3.0 cm and shallower, deeper than 3.0 cm) of the origin. Results : The origin of the vertebral arteries could be visualized in 97% on the right and in 92% on the left. The origin of the vertebral arteries could be visualized in 98.6%, 1.4%, and 0.0% in natural position, pushing the transducer, and pushing the shoulder of patient, respectively, at shallower than 3.0 cm on the right side. The origin of the vertebral arteries could be visualized in 81.2%, 14.6%, and 4.2% in natural position, pushing the transducer, and pushing the shoulder of patient, respectively, at deeper than 3.0 cm on the right side. The origin of the vertebral arteries could be visualized in 85.4%, 10.7%, and 3.9% in natural position, pushing the transducer, and pushing the shoulder of patient, respectively, at shallower than 3.0 cm on the left side. The origin of the vertebral arteries could be visualized in 55.7%, 30.4%, and 13.9% in natural position, pushing the transducer, and pushing the shoulder of patient, respectively, at deeper than 3.0 cm on the left side. Conclusion : If the examiner pushes the transducer toward a clavicle or pushes the shoulder of patient by the other hand, when the vertebral artery origin during the color doppler sonography is not visualized in natural position, visualization rate of the origin of the both vertebral arteries is increased.

• Journal of Chest Surgery
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• v.32 no.6
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• pp.525-531
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• 1999

Background: We analyzed five hundred patients who underwent either isolated or concomitant coronary artery bypass grafting(CABG) between November 1981 and June 1997. Material and Method: There were 330 males and 170 females with a mean age of 57.4$\pm$8.9 years. To evaluate the preoperative status, we performed electrocardiograghy, echocardiography, MIBI scan, Duplex sonogram, common blood test including CK and LDH and coronary angiography. Result: Preoperative clinical diagnoses were unstable angina in 282 (56.4%), stable angina in 141 (28.2%), postinfarction angina in 58 (11.6%), acute myocardial infarction in 8 (1.6%), variant angina in 7 (1.4%) and failed percutaneous transluminal coronary angioplasty in 4 (0.8%) patients. Preoperative angiographic diagnoses were three-vessel disease in 263 (52.6%), two-vessel disease in 93 (18.6%), one-vessel disease in 71 (14.2%), left main disease in 68 (13.6%), and others in 5 (1.0%) patients. Patients had various risk factors for coronary disease, and the frequency of the risk factors such as hypertension, diabetes and smoking showed increasing tendency year by year. We used saphenous vein grafts in 1143, internal thoracic artery grafts in 442, radial artery graft in 17, and gastroepiploic artery graft in 1 anastomosis. The mean number of grafts was 3.2$\pm$1.2 per patient. Concomitant operations were prosthetic valve replacement or valvuloplasty in 31, coronary endarterectomy and angioplasty in 27, left main coronary angioplasty in 13, carotid endarterectomy in 5, and neurologic problems, bleeding, and perioperative myocardial infarction. The mean follow-up period was 25$\pm$23 months and there were 5 cases of reoperation. Conclusion: We hope that the surgical results would improve with the accumulation of experience, application of new myocardial protection technique, and timely intervention of mechanical assisted devices.

• Journal of Chest Surgery
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• v.42 no.4
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• pp.441-446
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• 2009

Background: Side clamping of ascending aorta during proximal graft anastomosis in coronary bypassing surgery in-creases the risk of direct aortic injury as well as embolization of intimal atheroma. Heartstring proximal sealing system (Guidant Corporation, Santa Clara, Calif), developed to avoid aortic side clamping, may minimize risks of such complications. The aim of the current study is to compare the surgical outcomes of the two proximal anastomosis techniquesi.e., Heartstring system versus aortic side clamping in off pump coronary bypassing' surgery (OPCAB). Material and Method: From January 2003 to August 2008, 499 patients underwent OPCAB. Of them, proximal graft anastomosis was performed using Heartstring system in 182 patients (Group I) and conventional manual anastomosis in 317 patients (Group II). The two groups were compared for postoperative major complications and mortality. Result: Two groups showed similar characteristics in terms of preoperative demographic data, left ventricular ejection fraction, renal function and history of diabetes, hypertension and smoking. Although there was no inter-group difference in the history of cerebral ischemia (p=0.48), preoperative brain magnetic resonance angiography revealed greater incidence of severe carotid artery stenosis (>75% of lumen) in the Group I than in the. Group II (44.5% in the Group I and 30.0% in the Group II, p=0.003). There were no inter-group differences in postoperative mortality (p=0.40) and complications (p=0.47) including neurologic events (3 in the Group land 2 in the Group II, p=0.258). Whereas neurologic events all comprised transient ischemic attacks in the Group I, they comprised multiple embolic strokes in the Group II. One patient in the Group II experienced aortic dissection during proximal anastomosis which resulted in ascending aortic replacement. Conclusion: Although proximal anastomosis using Heartstring system did not show statistically significant benefit over aortic side clamping, the. absence of embolic stroke maybe a definite benefit which may be better defined through further studies over a larger cohort.