• Journal of Korean Neurosurgical Society
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• v.62 no.5
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• pp.536-544
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• 2019

Objective : The objective of this study was to evaluatelong-term radiologic prognosis and characteristics of in-stent stenosis (ISS) after stent assisted coiling (SAC) for cerebral aneurysm and analyze its risk factors. Methods : Radiological records of 362 cases of SAC during 10 years were retrospectively reviewed. Patients were included in this study if they had follow-up angiogram using catheter selected angiography at least twice. All subjected were followed up from 12 months to over 30 months. Of 120 patients, 123 aneurysms were enrolled. Patient data including age, sex, aneurysm size, neck size, procedural complication, kinds of stent, ISS associated symptom, ruptured state, location of ISS, degree of ISS, radiologic prognosis of ISS, follow-up period of time, and medical comorbidities such as hypertension, diabetes mellitus (DM), dyslipidemia, and smoking were collected.Statistical comparisons of group clinical characteristics were conducted for the total population. Results : Among 123 casesof aneurysm, 22 cases (17.9%) of ISS were revealed on follow-up angiography. Multiple stenting was performed in three cases and intra-procedural rupture occurred in two cases. Most cases were asymptomatic and symptomatic stenosis was identified in only one case. Sixteen cases were ruptured aneurysm. Mild stenosis was observed in 11 cases. Moderate stenosis was found in eight cases and severe stenosis was identified in three cases. Mean timing of identification of ISS was 8.90 months. The most common type was proximal type. Most cases were improved or not changed on follow-up angiography. Only one case was aggravated from mild stenosis to occlusion of parent artery. Mean follow-up period was 44.3 months. We compared risk factors and characteristic between ISS group and non-ISS group using univariate analysis. Multiple stenting was performed for three cases (13.6%) of the ISS group and four cases (4.0%) of the non-ISS group, showing no statistical difference between the two groups (p=0.108). Additionally, the proportion of patients who had more than two risk factors among four medical risk factors (hypertension, DM, dyslipidemia, and smoking) was higher in the ISS group than that in the non-ISS group, the difference between the two was not statistically significant either (31.8% vs. 12.9%, p=0.05). Conclusion : Clinical course and long-term prognosis of ISS might be benign. Most cases of ISS could be improved or not aggravated. Control of medical co-morbidity might be important. To the best of our knowledge, our study had more cases with longer follow-up period of time than other reports.

• Korean Journal of Radiology
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• v.19 no.6
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• pp.1161-1171
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• 2018

Objective: The aim of this study was to investigate diffusion tensor (DT) imaging-derived properties of benign oligemia, true "at risk" penumbra (TP), and the infarct core (IC) during the first 3 hours of stroke onset. Materials and Methods: The study was approved by the local animal care and use committee. DT imaging data were obtained from 14 rats after permanent middle cerebral artery occlusion (pMCAO) using a 7T magnetic resonance scanner (Bruker) in room air. Relative cerebral blood flow and apparent diffusion coefficient (ADC) maps were generated to define oligemia, TP, IC, and normal tissue (NT) every 30 minutes up to 3 hours. Relative fractional anisotropy (rFA), pure anisotropy (rq), diffusion magnitude (rL), ADC (rADC), axial diffusivity (rAD), and radial diffusivity (rRD) values were derived by comparison with the contralateral normal brain. Results: The mean volume of oligemia was $24.7{\pm}14.1mm^3$, that of TP was $81.3{\pm}62.6mm^3$, and that of IC was $123.0{\pm}85.2mm^3$ at 30 minutes after pMCAO. rFA showed an initial paradoxical 10% increase in IC and TP, and declined afterward. The rq, rL, rADC, rAD, and rRD showed an initial discrepant decrease in IC (from -24% to -36%) as compared with TP (from -7% to -13%). Significant differences (p < 0.05) in metrics, except rFA, were found between tissue subtypes in the first 2.5 hours. The rq demonstrated the best overall performance in discriminating TP from IC (accuracy = 92.6%, area under curve = 0.93) and the optimal cutoff value was -33.90%. The metric values for oligemia and NT remained similar at all time points. Conclusion: Benign oligemia is small and remains microstructurally normal under pMCAO. TP and IC show a distinct evolution of DT-derived properties within the first 3 hours of stroke onset, and are thus potentially useful in predicting the fate of ischemic brain.

• Journal of Korean Neurosurgical Society
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• v.64 no.5
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• pp.732-739
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• 2021

Objective : Early successful reperfusion is associated with favorable outcomes in acute ischemic stroke (AIS). The purpose of this study was to achieve successful recanalization by a combined mechanical thrombectomy technique, the Aspiration-Retriever Technique for Stroke (ARTS), which is composed of a flexible large lumen distal access catheter and a retrievable stent as the first-line strategy of mechanical thrombectomy. Methods : We retrospectively reviewed 62 patients with AIS who underwent mechanical thrombectomy from 2018 to 2019 at our institute by a senior neurointerventionalist. Among them, patients who were treated using the ARTS technique with the soft torqueable catheter optimized for intracranial access (SOFIA^®; MicroVention-Terumo, Tustin, CA, USA) as the first-line treatment were included. Patients who had tandem occlusions or underlying intracranial artery stenosis were excluded. The angiographic and clinical outcomes were evaluated. The angiographic outcome was analyzed by the rate of successful recanalization, defined as a Thrombolysis in Cerebral Infarction score of 2b or 3 at the end of all procedures and the rate of successfully achieving the first pass effect (FPE), defined as complete recanalization with a single pass of the device. The clinical outcomes included the National Institutes of Health Stroke Scale (NIHSS) score, modified Rankin Scale (mRS), and mortality. Results : A total of 27 patients (mean age, 59.3 years) fulfilled the inclusion criteria. The successful recanalization rate was 96% (n=26) while the FPE rate was 41% (n=11). The mean post-procedural NIHSS change was -3.0. Thirteen patients (48%) showed good clinical outcomes after thrombectomy with the ARTS technique (mRS at 90 days ≤2). Postoperative complications occurred in seven of 25 patients : hemorrhagic transformation in six patients (22%) and distal embolization in one patient (4%). Mortality was 15% (n=4). Conclusion : Although the clinical outcomes using the ARTS technique with a flexible large lumen distal access catheter performed as the frontline thrombectomy in patients with AIS were not significantly superior than those of other studies, this study showed a high rate of successful endovascular recanalization which was comparable to that of other studies. Therefore, ARTS using the SOFIA^® catheter can be considered as the first choice of treatment for AIS due to large vessel occlusion.

• Journal of Korean Neurosurgical Society
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• v.64 no.5
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• pp.693-704
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• 2021

Objective : Endovascular mechanical thrombectomy (MT) has been regarded as one of the standard treatments for acute ischemic stroke caused by large vessel occlusion. Despite the wide use of stent retrievers for MT, arterial intimal damage caused when deployed stent is pulled has been a certain disadvantage. We hypothesized that statin could protect and stabilize vessel damage after endovascular MT using a stent retriever. In this animal study, we observed the protective effects of the statins towards MT-induced vessel wall injury. Methods : Twenty-eight carotid arteries of fourteen rabbits were used in the experiments with MT using stent retriever. We divided the rabbits into four groups as follows : group 1, negative control; group 2, positive control; group 3, statin before MT; and group 4, statin after MT. After MT procedures, we harvested the carotid arteries and performed histomorphological and immunohistochemical analyses. Results : In histomorphological analysis with hematoxylin and eosin and Masson's trichrome stain, significant intimal thickening (p<0.05) was observed in the positive control (group 2), compared to in the negative control (group 1). Intimal thickening was improved in the statin-administered groups (groups 3 and 4 vs. group 2, p<0.05). We also observed that statin administration after MT (group 4) resulted in a more effective decrease in intimal thickness than statin administration before MT (group 3) (p<0.05). We performed immunohistochemical analysis with the antibodies for tumor necrosis factor-alpha (TNF-α), cluster of differentiation (CD)11b, and CD163. In contrast to the negative control (group 1), the stained percentage areas of all immunological markers were markedly increased in the positive control (group 2) (p<0.05). Based on statin administration, the percentage area of TNF-α staining was significantly reduced (p<0.05) in group 3, compared to the positive control group (group 2). However, significant differences were not observed for CD11b and CD163 staining. In group 4, no significant differences were observed for TNF-α, CD11b, and CD163 staining (p≥0.05). The differences in the percentage areas of the different markers between the statin-administered groups (groups 3 and 4) were also not revealed. Conclusion : We presented that statin administration before and after MT exerted protective effects towards vessel wall injury. The efficacy of statins was greater post-administration than pre-administration. Thus, statin administration in routine prescriptions in the peri-procedural period is strongly advised.

• Journal of Physiology & Pathology in Korean Medicine
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• v.36 no.2
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• pp.59-65
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• 2022

Rodent model for chronic cerebral hypoperfusion caused by bilateral carotid artery occlusion (BCAO) show clinically relevant evidences for vascular dementia and impairments of synaptic plasticity in the hippocampus. The purpose of this study was to evaluate effect of fermented garlic (F-Garlic) extract with NO metabolites on cognitive behaviors, synaptic plasticity, and molecular events in the hippocampus following BCAO. Adult male Sprague-Dawley rats were randomly divided three experimental groups into: control+water; BCAO+water; BCAO+F-Garlic. Animals were treated with oral administration of F-Garlic in tap water as a drinking water after surgery for 4 weeks. On passive avoidance test and Y-maze test, BCAO+water showed a significant decrease in step-through latency and spontaneous alteration, indicating deficit of hippocampal memory formation but the treatment of F-Garlic significantly increased these cognitive behaviors. In control+water, a robust increase in the amplitude of evoked field excitatory postsynaptic potentials was observed by theta burst stimulation to hippocampal neural circuit indicating formation of long-term potentiation (LTP) in the hippocampal CA1. BCAO+water showed a highly significant deficit in LTP induction 4 weeks after BCAO. On other hand, daily oral administration of F-Garlic extract caused the marked preservation of LTP induction. Moreover, parvalbumin was markedly reduced in the CA1, especially, in the stratum radiatum of BCAO+water. In contrast, BCAO+F-Garlic mitigate a significantly reduction of the parvalbumin. In summary, these results suggest that daily oral administration of F-Garlic extract can ameliorate cognitive memory deficit through the preservation of synaptic plasticity and interneurons integrity in the hippocampus in rodent model of chronic cerebral hypoperfusion.

• Journal of Ginseng Research
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• v.47 no.2
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• pp.199-209
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• 2023

Background: Due to the interrupted blood supply in cerebral ischemic stroke (CIS), ischemic and hypoxia results in neuronal depolarization, insufficient NAD+, excessive levels of ROS, mitochondrial damages, and energy metabolism disorders, which triggers the ischemic cascades. Currently, improvement of mitochondrial functions and energy metabolism is as a vital therapeutic target and clinical strategy. Hence, it is greatly crucial to look for neuroprotective natural agents with mitochondria protection actions and explore the mediated targets for treating CIS. In the previous study, notoginseng leaf triterpenes (PNGL) from Panax notoginseng stems and leaves was demonstrated to have neuroprotective effects against cerebral ischemia/reperfusion injury. However, the potential mechanisms have been not completely elaborate. Methods: The model of middle cerebral artery occlusion and reperfusion (MCAO/R) was adopted to verify the neuroprotective effects and potential pharmacology mechanisms of PNGL in vivo. Antioxidant markers were evaluated by kit detection. Mitochondrial function was evaluated by ATP content measurement, ATPase, NAD and NADH kits. And the transmission electron microscopy (TEM) and pathological staining (H&E and Nissl) were used to detect cerebral morphological changes and mitochondrial structural damages. Western blotting, ELISA and immunofluorescence assay were utilized to explore the mitochondrial protection effects and its related mechanisms in vivo. Results: In vivo, treatment with PNGL markedly reduced excessive oxidative stress, inhibited mitochondrial injury, alleviated energy metabolism dysfunction, decreased neuronal loss and apoptosis, and thus notedly raised neuronal survival under ischemia and hypoxia. Meanwhile, PNGL significantly increased the expression of nicotinamide phosphoribosyltransferase (NAMPT) in the ischemic regions, and regulated its related downstream SIRT1/2/3-MnSOD/PGC-1α pathways. Conclusion: The study finds that the mitochondrial protective effects of PNGL are associated with the NAMPT-SIRT1/2/3-MnSOD/PGC-1α signal pathways. PNGL, as a novel candidate drug, has great application prospects for preventing and treating ischemic stroke.

• Korean Journal of Clinical Laboratory Science
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• v.54 no.4
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• pp.256-264
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• 2022

Ischemic stroke is caused by an occlusion by a thrombus or embolus in a cerebral artery, preventing oxygenated blood from reaching the brain and causing the necrosis of nerve cells. This paper summarizes the serum candidate markers associated with cardiovascular disease and atrial fibrillation (AF) disease that enable an early diagnosis of ischemic stroke studied thus far and compares the odds ratio (OR) of each marker. This study examined the effect size of these serum candidate markers using meta-analysis techniques. The academic database search screening for articles containing the keywords "cardiovascular disease," "atrial fibrillation," "ischemic stroke," and "serum marker" was limited to results for patients with ischemic stroke. The most derived markers in this study were N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), D-dimer, C-reactive protein (CRP), and glial fibrillary acidic protein (GFAP), the rest being investigated individually. In conclusion, NT-pro-BNP appears to be very useful for the early diagnosis of ischemic stroke. Primarily, it is a marker of AF, and more AF markers will be uncovered and studied in the future.

• Journal of agriculture & life science
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• v.50 no.3
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• pp.129-139
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• 2016

Curcumin plays a protective role in brain injury through its anti-oxidant and anti-inflammatory activities. Moreover, peroxiredoxin-5 exerts a protective effect against oxidative stress. The aim of this study was to investigate whether curcumin modulated the peroxiredoxin-5 expression in focal cerebral ischemic animal model. Middle cerebral artery occlusion(MCAO) was performed to induce cerebral ischemic injury in rats. Adult male rats were injected intraperitoneally with vehicle or curcumin(50mg/kg B.W.) 1 h after MCAO and cerebral cortex tissues were collected 24 h after MCAO. Photographs of hematoxylin and eosin staining showed that MCAO induced necrotic changes with scalloped shrunken form and apoptotic changes with nuclear chromatin condensations. However, curcumin treatment attenuated MCAO-induced histopathological changes. Moreover, this study clearly showed that peroxiredoxin-5 expression was decreased in MCAO operated animal with vehicle using a proteomics approach. However, this decrease in peroxiredoxin-5 expression was attenuated by curcumin treatment. Reverse-transcription PCR and Western blot analyses confirmed that curcumin treatment alleviated the MCAO injury-induced decrease in peroxiredoxin-5 expression(p<0.05). These results demonstrated that curcumin regulates peroxiredoxin-5 expression in MCAO animal model. In conclusion, our findings suggest that curcumin exerts a neuroprotective effect in cerebral ischemia by attenuating the MCAO-induced decrease in peroxiredoxin-5 expression.

• Korean Journal of Radiology
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• v.21 no.5
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• pp.582-587
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• 2020

Objective: Endovascular thrombectomy (EVT) fails in approximately 20% of anterior circulation large vessel occlusion (AC-LVO). Nonetheless, the factors that affect clinical outcomes of non-recanalized AC-LVO despite EVT are less studied. The purpose of this study was to identify the factors affecting clinical outcomes in non-recanalized AC-LVO patients despite EVT. Materials and Methods: This was a retrospective analysis of clinical and imaging data from 136 consecutive patients who demonstrated recanalization failure (modified thrombolysis in cerebral ischemia [mTICI], 0-2a) despite EVT for AC-LVO. Data were collected in prospectively maintained registries at 16 stroke centers. Collateral status was categorized into good or poor based on the CT angiogram, and the mTICI was categorized as 0-1 or 2a on the final angiogram. Patients with good (modified Rankin Scale [mRS], 0-2) and poor outcomes (mRS, 3-6) were compared in multivariate analysis to evaluate the factors associated with a good outcome. Results: Thirty-five patients (25.7%) had good outcomes. The good outcome group was younger (odds ratio [OR], 0.962; 95% confidence interval [CI], 0.932-0.992; p = 0.015), had a lower incidence of hypertension (OR, 0.380; 95% CI, 0.173-0.839; p = 0.017) and distal internal carotid artery involvement (OR, 0.149; 95% CI, 0.043-0.520; p = 0.003), lower initial National Institute of Health Stroke Scale (NIHSS) (OR, 0.789; 95% CI, 0.713-0.873; p < 0.001) and good collateral status (OR, 13.818; 95% CI, 3.971-48.090; p < 0.001). In multivariate analysis, the initial NIHSS (OR, 0.760; 95% CI, 0.638-0.905; p = 0.002), good collateral status (OR, 14.130; 95% CI, 2.264-88.212; p = 0.005) and mTICI 2a recanalization (OR, 5.636; 95% CI, 1.216-26.119; p = 0.027) remained as independent factors with good outcome in non-recanalized patients. Conclusion: Baseline NIHSS score, good collateral status, and mTICI 2a recanalization remained independently associated with clinical outcome in non-recanalized patients. mTICI 2a recanalization would benefit patients with good collaterals in non-recanalized AC-LVO patients despite EVT.

• Korean Journal of Radiology
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• v.23 no.4
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• pp.446-454
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• 2022

Objective: To evaluate whether hyperoxia-induced ΔR₁ (hyperO₂ΔR₁) can accurately identify histological infarction in an acute cerebral stroke model. Materials and Methods: In 18 rats, MRI parameters, including hyperO₂ΔR₁, apparent diffusion coefficient (ADC), cerebral blood flow and volume, and ¹⁸F-fluorodeoxyglucose uptake on PET were measured 2.5, 4.5, and 6.5 hours after a 60-minutes occlusion of the right middle cerebral artery. Histological examination of the brain was performed immediately following the imaging studies. MRI and PET images were co-registered with digitized histological images. The ipsilateral hemisphere was divided into histological infarct (histological cell death), non-infarct ischemic (no cell death but ADC decrease), and nonischemic (no cell death or ADC decrease) areas for comparisons of imaging parameters. The levels of hyperO₂ΔR₁ and ADC were measured voxel-wise from the infarct core to the non-ischemic region. The correlation between areas of hyperO₂ΔR₁-derived infarction and histological cell death was evaluated. Results: HyperO₂ΔR₁ increased only in the infarct area (p ≤ 0.046) compared to the other areas. ADC decreased stepwise from non-ischemic to infarct areas (p = 0.002 at all time points). The other parameters did not show consistent differences among the three areas across the three time points. HyperO₂ΔR₁ sharply declined from the core to the border of the infarct areas, whereas there was no change within the non-infarct areas. A hyperO₂ΔR₁ value of 0.04 s^-1 was considered the criterion to identify histological infarction. ADC increased gradually from the infarct core to the periphery, without a pronounced difference at the border between the infarct and non-infarct areas. Areas of hyperO₂ΔR₁ higher than 0.04 s^-1 on MRI were strongly positively correlated with histological cell death (r = 0.862; p < 0.001). Conclusion: HyperO₂ΔR₁ may be used as an accurate and early (2.5 hours after onset) indicator of histological infarction in acute stroke.