• Journal of Veterinary Science
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• v.23 no.6
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• pp.84.1-84.15
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• 2022

Background: Stroke is caused by disruption of blood supply and results in permanent disabilities as well as death. Chlorogenic acid is a phenolic compound found in various fruits and coffee and exerts antioxidant, anti-inflammatory, and anti-apoptotic effects. Objectives: The purpose of this study was to investigate whether chlorogenic acid regulates the PI3K-Akt-Bad signaling pathway in middle cerebral artery occlusion (MCAO)-induced damage. Methods: Chlorogenic acid (30 mg/kg) or vehicle was administered peritoneally to adult male rats 2 h after MCAO surgery, and animals were sacrificed 24 h after MCAO surgery. Neurobehavioral tests were performed, and brain tissues were isolated. The cerebral cortex was collected for Western blot and immunoprecipitation analyses. Results: MCAO damage caused severe neurobehavioral disorders and chlorogenic acid improved the neurological disorders. Chlorogenic acid alleviated the MCAO-induced histopathological changes and decreased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells. Furthermore, MCAO-induced damage reduced the expression of phospho-PDK1, phospho-Akt, and phospho-Bad, which was alleviated with administration of chlorogenic acid. The interaction between phospho-Bad and 14-3-3 levels was reduced in MCAO animals, which was attenuated by chlorogenic acid treatment. In addition, chlorogenic acid alleviated the increase of cytochrome c and caspase-3 expression caused by MCAO damage. Conclusions: The results of the present study showed that chlorogenic acid activates phospho-Akt and phospho-Bad and promotes the interaction between phospho-Bad and 14-3-3 during MCAO damage. In conclusion, chlorogenic acid exerts neuroprotective effects by activating the Akt-Bad signaling pathway and maintaining the interaction between phospho-Bad and 14-3-3 in ischemic stroke model.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.25 no.3
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• pp.180-193
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• 2022

Pediatric inflammatory bowel disease (PIBD) is a multisystem disorder characterized by intestinal and extraintestinal manifestations and complications. Cerebrovascular events (CVE) are rare extraintestinal complications in patients with PIBD. Statistics show that 3.3% patients with PIBD and 1.3-6.4% adult patients with inflammatory bowel disease (IBD) experience CVE during the course of the disease. Therefore, this study aimed to review the records of children with IBD who developed CVE during the course of the disease. We retrospectively reviewed 62 cases of PIBD complicated by CVE. The mean patient age at the time of thrombotic events was 12.48±4.13 years. The incidence of ulcerative colitis was significantly higher than that of Crohn's disease (43 [70.5%] vs. 13 [21.3%] patients). Most patients (87.93%) were in the active phase of IBD at the time of CVE. The mean time interval between the onset of IBD and CVE was 20.84 weeks. Overall, 11 (26.83%) patients showed neurological symptoms of CVE at disease onset. The most frequent symptom on admission was persistent and severe headaches (67.85%). The most common site of cerebral venous thrombosis was the transverse sinuses (n=23, 53.48%). The right middle cerebral artery (n=3, 33.34%) was the predominant site of cerebral arterial infarction. Overall, 41 (69.49%) patients who were mostly administered unfractionated heparin or low-molecular-weight heparin (56.09%) recovered completely. Patients with IBD are at a risk of thromboembolism. CVE may be the most common type of thromboembolism. Based on these findings, the most common risk factor for CVE is IBD flares. In patients with CVE, anticoagulant therapy with heparin, followed by warfarin, is necessary.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.62-62
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• 2003

It is now convincing that free radical generation is involved in the pathophy siological mechanisms of ischemic stroke, particularly in ischemia-reperfusion injury. The present study, therefore, examined neuroprotective effect of aloesin isolated from Aloe vera, which was known to have antioxidative activity, in a rat model of transient focal cerebral ischemia. Transient focal cerebral ischemia was induced by occlusion of middle cerebral artery for 2 hr with a silicone-coated 4-0 nylon monofilament in male Sprague-Dawley rats under isoflurane anesthesia Aloesin (1, 3, 10, 30 and 50 mg/kg/injection) was administered intravenously 3 times at 0.5, 2 and 4 hr after onset of ischemia. Neurological score was measured 24 hr after onset of ischemia immediately before sacrifice. Seven serial coronal slices of the brain were stained with 2,3,5-triphenyltetrazolium chloride and infarct size was measured using a computerized image analyzer. Treatment with the close of 1 or 50 mg/kg did not significantly reduce infarct volume compared with the saline vehicle-treated control group. However, treatments with the closes of 3 and 10 mg/kg significantly reduced both infarct volume and edema by approximately 47% compared with the control group, producing remarkable behavioral recovery effect. Treatment with the close of 30 mg/kg also significantly reduced infarct volume to a lesser extent by approximately 33% compared with the control group, but produced similar degree of behavioral recovery effect. In addition, general pharmacological studies showed that aloesin was a quite safe compound. The results suggest that aloesin can serve as a lead chemical for the development of neuroprotective agents by providing neuroprotection against focal ischemic neuronal injury.

• The Journal of the Society of Stroke on Korean Medicine
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• v.7 no.1
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• pp.59-64
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• 2006

Objective : This study was aimed to investigated the warning signs and its relationship with the other characteristics in acute stroke patients. Methods : Three-hundred sixty three acute stroke patients were recuited in the oriental medical hospitals of 3 universities located in metropolitan region from October in 2005 to October in 2006. We evaluated their stroke type with brain MRI, their waring signs, and general characteristics such as age, sex, past history, risk factor, etc. Result : Of the 363 patient, 138(38%) patients were experience of warning signs. The frequency of Stress were found more in experience of warning signs than none of them. Warning signs were more common in Large Artery Atherosclerosis than in the other etiology. Conclusion : Although a concrete conclusion can hardly be drawn from this study, it reminds physicians of the importance of warning signs which their patients appeal. For the further investigation, it seems to be necessary to construct fundamental databases for stroke by increasing the number of patients and by examination into the etiology and location.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.28 no.1
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• pp.34-41
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• 2024

Backgrounds/Aims: Liver transplantation (LT) provides a favorable outcome for patients with hepatocellular carcinoma (HCC) and was launched in Vietnam in 2004. In this study, we evaluated the short-term and long-term outcomes of LT and its risk factors. Methods: This retrospective study analyzed HCC patients who underwent LT at Viet Duc University hospital, Vietnam, from 01/2012-03/2022. The following data were gathered: demographics, virus infection, tumor characteristics, alpha-fetoprotein (AFP) level, Child-Pugh and MELD scores, selection criteria, type of LT, complications, 30-day mortality, and disease-free and overall survival (DFS and OS). Results: Fifty four patients were included, the mean age was 55.39 ± 8.46 years. Nearly 90% had hepatitis B virus-related HCC. The median (interquartile range) AFP level was 16.2 (88.7) ng/mL. The average MELD score was 10.57 ± 5.95; the rate of Child-Pugh A and B were 70.4% and 18.5%, respectively. Nearly 40% of the patients were within Milan criteria, brain-dead donor was 83.3%. Hepatic and portal vein thrombosis occurred in 0% and 1.9%, respectively; hepatic artery thrombosis 1.9%, biliary leakage 5.6%, and postoperative hemorrhage 3.7%. Ninety-day mortality was 5.6%. Five-year DFS and OS were 79.3% and 81.4%, respectively. MELD score and ChildPugh score were predictive factors for DFS and OS (p < 0.05). In multivariate analysis, Child-Pugh score was the only significant factor (p < 0.05). Conclusions: In Vietnam, LT is an effective therapy for HCC with an acceptable complication rate, mortality rate, and good survival outcomes, and should be further encouraged.

• 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.

• 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.

• 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 Nuclear Medicine
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• v.36 no.6
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• pp.357-367
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• 2002

Purpose: While cerebral blood flow and cerebrovascular reserve could be evaluated with basal/acetazolamide Tc-99m-HMPAO SPECT in cerebrovascular disease, objective quantification is necessary to assess the efficacy of the revascularization. In this study we adopted the SPM method to quantify basal cerebral blood flow and cerebrovascular reserve on basal/acetazolamide SPECT in assessment of the patients who underwent bypass surgery for linternal carotid artery (ICA) stenosis. Materials and Methods: Twelve patients ($51{\pm}15$ years) with ICA stenosis were enrolled. Tc-99m-HMPAO basal/acetazolamide perfusion SPECT was peformed before and after bypass surgery. After spatia1 and count normalization to cerebellum, basal cerebral blood flow and cerebrovascular reserve were compared with 21 age-matched normal controls and postoperative changes of regional blood flow and reserve were assessed by Statistical Parametric Mapping method. Mean pixel values of each brain region were calculated using probabilistic anatomical map of lobes. Perfusion reserve was defined as the % changes after acetazolamide over basal counts. Results: Preoperative cerebral blood flow and cerebrovascular reserve were significantly decreased in involved ICA territory, comparing with normal control (p<0.05). Postoperative improvement of cerebral blood flow and cerebrovascular reserve was observed in grafted ICA territories, but cerebrovasculr reserve remained with significant difference with normal control. Improvement of the cerebrovascular reserve was most prominent in the superior temporal and the angular gyrus, nearest to the anastomosis sites. Conclusion: Using SPM quantification method on hasal/acetazolamide Tc-99m-HMPAO SPECT, the cerebral blood flow and cerebrovascular reserve could be assessed before revascularization and so could the efficacy of the bypass surgery.

• Nuclear Medicine and Molecular Imaging
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• v.42 no.1
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• pp.8-16
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• 2008

Purpose: To assess the effect of extracranial-intracranial (EC-IC) bypass surgery on hemodynamic improvement, we evaluated serial regional cerebral hemodynamic change of the middle cerebral artery (MCA) in symptomatic patients with atherosclerotic occlusion of the internal carotid artery (ICA) or MCA using $^{99m}Tc$-ECD acetazolamide stress brain perfusion SPECT (Acetazolamide SPECT). Materials and Methods: The patients who had suffered a recent stroke with atherosclerotic ICA or MCA occlusion underwent EC-IC bypass surgery and Acetazolamide SPECT at 1 week before and three to six months after surgery. For image analysis, attenuation corrected images were spatially normalized to SPECT templates with SPM2. Anatomical automated labeling was applied to calculate mean counts of each Volume-Of-Interest (VOI). Seven VOIs of bilateral frontal, parietal, temporal regions of the MCA territory and the ipsilateral cerebellum were defined. Using mean counts of 7 VOIs, cerebral perfusion index and perfusion reserve index were calculated. Results: Seventeen patients (M:F =12:5, mean age $53{\pm}2yr$) were finally included in the analysis. The cerebral blood flow of the parietal region increased at 1 week (p = 0.003) and decreased to the preoperative level at 3-6 months (p = 0.003). The cerebrovascular reserve of the frontal and parietal regions increased significantly at 1 week after surgery (p<0.01) and improved further at 3-6 months. Conclusion: Cerebrovascular reserve of the MCA territory was significantly improved at early postoperative period after EC-IC bypass and kept improved state during long-term follow-up, although cerebral blood flow did not significantly improved. Therefore, cerebrovascular reserve may be a good indicator of postoperative hemodynamic improvement resulted from bypass effect.