• Biomolecules & Therapeutics
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• v.27 no.3
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• pp.290-301
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• 2019

Paeonol has neuroprotective function, which could be useful for improving central nervous system disorder. The purpose of this study was to characterize the functional mechanism involved in brain transport of paeonol through blood-brain barrier (BBB). Brain transport of paeonol was characterized by internal carotid artery perfusion (ICAP), carotid artery single injection technique (brain uptake index, BUI) and intravenous (IV) injection technique in vivo. The transport mechanism of paeonol was examined using conditionally immortalized rat brain capillary endothelial cell line (TR-BBB) as an in vitro model of BBB. Brain volume of distribution (VD) of [$^3H$]paeonol in rat brain was about 6-fold higher than that of [$^{14}C$]sucrose, the vascular space marker of BBB. The uptake of [$^3H$]paeonol was concentration-dependent. Brain volume of distribution of paeonol and BUI as in vivo and inhibition of analog as in vitro studies presented significant reduction effect in the presence of unlabeled lipophilic compounds such as paeonol, imperatorin, diphenhydramine, pyrilamine, tramadol and ALC during the uptake of [$^3H$]paeonol. In addition, the uptake significantly decreased and increased at the acidic and alkaline pH in both extracellular and intracellular study, respectively. In the presence of metabolic inhibitor, the uptake reduced significantly but not affected by sodium free or membrane potential disruption. Similarly, paeonol uptake was not affected on OCTN2 or rPMAT siRNA transfection BBB cells. Interestingly. Paeonol is actively transported from the blood to brain across the BBB by a carrier mediated transporter system.

• Journal of Korean Neurosurgical Society
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• v.44 no.5
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• pp.295-302
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• 2008

Objective: Premorbid demographic backgrounds of injured individuals are likely to reflect more accurately the status of patients with traumatic brian injury (TBI) than clinical factors. However, the concrete study about the relationship between the demographic factors and neurocognitive function in TBI patients has not been reported. The object of this study was to evaluate the effect of premorbid demographic factors on the recovery of neurocognitive function following TBI. Methods: From July 1998 to February 2007, 293 patients (male: 228, female: 65) with a history of head injury, who had recovered from the acute phase, were selected from our hospital to include in this study. We analyzed the effect of premorbid demographic factors including age, sex, educational level and occupation on the recovery of neurocognitive function in each TBI subgroup as defined by Glasgow Coma Scale (GCS) score. Intelligence and memory are components of neurocognitive function, and the Korean Wechsler Intelligence Scale (K-WAIS) and the Korean memory assessment scale (K-MAS) were used in this study. The results were considered significant at p<0.05. Results: The higher level of education was a good prognostic factor for intelligence regardless of GCS score and younger age group showed a better result for memory with an exception of severe TBI group. In the severe TBI group, the meaningful effect of demographic factors was not noted by the cause of influence of severe brain injury. Conclusion: The demographic factors used in this study may be helpful for predicting the precise prognosis and developing an appropriate rehabilitation program for TBI patients.

• Journal of Korean Neurosurgical Society
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• v.57 no.1
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• pp.1-5
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• 2015

Objective : Cerebral vessels, such as intracerebral perforating arterioles isolated from rat brain, have been widely used as an ex vivo model to study the cerebrovascular function associated with cerebrovascular disorders and the therapeutic effects of various pharmacological agents. These perforating arterioles, however, have demonstrated differences in the vascular architecture and reactivity compared with a larger leptomeningeal artery which has been commonly implicated in cerebrovascular disease. In this study, therefore, we developed the method for studying cerebrovascular function utilizing the olfactory artery isolated from the mouse brain. Methods : The olfactory artery (OA) was isolated from the C57/BL6 wild-type mouse brain. After removing connective tissues, one side of the isolated vessel segment (approximately $-500{\mu}m$ in length) was cannulated and the opposite end of the vessel was completely sealed while being viewed with an inverted microscope. After verifying the absence of pressure leakage, we examined the vascular reactivity to various vasoactive agents under the fixed intravascular pressure (60 mm Hg). Results : We found that the isolated mouse OAs were able to constrict in response to vasoconstrictors, including KCl, phenylephrine, endothelin-1, and prostaglandin $PGH_2$. Moreover, this isolated vessel demonstrated vasodilation in a dose-dependent manner when vasodilatory agents, acetylcholine and bradykinin, were applied. Conclusion : Our findings suggest that the isolated olfactory artery would provide as a useful ex vivo model to study the molecular and cellular mechanisms of vascular function underlying cerebrovascular disorders and the direct effects of such disease-modifying pathways on cerebrovascular function utilizing pharmacological agents and genetically modified mouse models.

• Journal of Life Science
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• v.30 no.11
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• pp.939-946
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• 2020

Stroke is one of the leading causes of neurological disability worldwide and stroke patients exhibit a range of motor, cognitive, and psychiatric impairments. GPR88 is an orphan G protein-coupled receptor (GPCR) that is highly expressed in striatal medium spiny neurons; its deletion results in poor motor coordination and motor learning. There are currently no studies on the involvement of GPR88 in stroke or in post-stroke brain function recovery. In this study, we found a decrease in GPR88 protein and mRNA expression levels in an ischemic mouse model using Western blot and real-time PCR, respectively. In addition, we observed that, among the three types of cells derived from the brain (brain microvascular endothelial cells, BV2 microglial cells, and HT22 hippocampal neuronal cells), the expression of GPR88 was highest in HT22 neuronal cells, and that GPR88 expression was downregulated in HT22 cells under oxygen-glucose deprivation (OGD) conditions. Moreover, pretreatment with RTI- 13951-33 (10 mg/kg), a brain-penetrant GPR88 agonist, ameliorated brain injury following ischemia, as evidenced by improvements in infarct volume, vestibular-motor function, and neurological score. Collectively, our results suggest that GPR88 could be a potential drug target for the treatment of central nervous system (CNS) diseases, including ischemic stroke.

• Korean Journal of Biological Psychiatry
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• v.14 no.1
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• pp.61-67
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• 2007

Objectives : The purpose of this study was to test stage model in Traumatic Brain Injury(TBI) patients. According to the stage model, attention deficits which is basic stage in information processing lead to memory disturbance and subsequently affect higher-order cognitive function such as memory, decision-making, abstract thinking, and judgement related to executive function. Therefore, it was hypothesized that attention affect recall(retrieval efficacy) related to executive function mostly relative to other cognitive function, in TBI patients with low executive function. Methods : Participants were referred to a TBI clinic and then was rated on K-WAIS and Executive Intelligence Test(EXIT). Participants were divided into two groups according to Executive IQ(EIQ) score, which of high function group(N=67) was more than 80(above low average) and of low function group(N=52) was under 80 (under borderline). To test the stage model, using hierarchical regression analysis, recall(retrieval efficacy) was regressed on 3 subscales(attention, verbal, visuospatial scale) after controlling for IQ according to each group. Furthermore, the mediation effect of attention between retrieval efficacy and verbal, visuospatial score was analyzed. Results : In the low function group, only attention area predicted significantly recall(retrieval efficacy), indicating that lower attention were related to lower EIQ after controlling for IQ. In the high function group, no area predicted significantly retrieval efficacy. In the low function group, verbal and visuospatial scale did not predicted significantly retrieval efficacy, indicating that there was no evidences supporting the mediation model. Conclusion : Only attention affect retrieval efficacy in TBI patients with low executive function. But, the mediation effect of attention between retrieval efficacy and verbal and visuospatial scale was not tested in the low function group. These results implied that stage model was tested partially. In treating cognitive deficit in TBI patients, it is necessary to develop cognitive rehabilitation program based on stage model. Furthermore, it is necessary to necessary to test mediation model in the future study.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.13 no.7
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• pp.2949-2954
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• 2012

This study was to examine the correlation between the brain function of adult suffering from obesity and the level of their obesity based on brainwave measurements. Based on the result of Body Composition Analysis (BCA) examination, population of 651 overweight pupils was chosen from June 2011 to December of 2012 in S city, I hospital. These patients were measured by timeseries linear analysis for their brain function and observed via brainwave activities. The results have been thus far; first, as their BMI (Body Mass Index) and level of obesity (body fat percentage) were higher, degree of mental stress and resistant to stress marked lower. These results prove that by managing the stress resistant ability and attention ability, self-controlling ability, one can expect a positive effect on finding a methods to ease the obese-related problems.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.3
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• pp.760-764
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• 2005

This research was performed to investigate protective effect of Sophora Subprostrata fractions against focal ischemic brain damage after middle cerebral artery(MCA) occlusion. Rats were divided into six groups: MCA-occluded group(Control); each administered groups with Sophora Subprostrata total phase(Total), Sophora Subprostrata Aqueous phase (Aqueous), Sophora Subprostrata BuOH phase(BuOH), and Sophora Subprostrata Alkaloid phase(Alkaloid) after MCA-occlusion; sham-operated group(Sham). The right MCA was occluded by A poly-L-lysine coated 4-0 nylon suture thread through the internal carotid artery permanently. Sophora Subprostrata and fractions were administered orally(5mg/ml) for 7 days after MCA-occlusion. The behavior of ischemic rats were examined at 24 hours, 3, 5 and 7 days after MCA-occlusion from the views of 4 different aspects: posture & balance tests(4 subtests), reflex tests(6 subtests), muscle-tone tests(3 subtests), and foot-fault test. The results showed that 1) in muscle tone test, Sophora Subprostrata total phase only increased reduced muscle tone function from 3 to 7 days, 2) in reflex test, Sophora Subprostrata total and Aqueous phase increased fast recovery from 24 hours and 3 days, 3) in posture & balance test, Sophora Subprostrata total and Aqueous phase increased fast recovery from 24 hours, and Sophora Subprostrata BuOH and Alkaloid phase increased posture & balance function from 3 days, but 4) in motor function test, Sophora Subprostrata did not show effective recovery compared with control group. In conclusion, Sophora Subprostrata has protective effects against brain damage at the early stage of focal cerebral ischemia. Sophora Subprostrata total and Aqueous phase produced more pronounced protective effect against focal ischemic brain damage.

• Korean Journal of Exercise Nutrition
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• v.24 no.4
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• pp.15-23
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• 2020

[Purpose] Lactate is a principal energy substrate for the brain during exercise. A single bout of high-intensity interval exercise (HIIE) can increase the blood lactate level, brain lactate uptake, and executive function (EF). However, repeated HIIE can attenuate exercise-induced increases in lactate level and EF. The lactate levels in the brain and blood are reported to be correlated with exercise-enhanced EF. However, research is yet to explain the cause-and-effect relationship between lactate and EF. This study examined whether lactate consumption improves the attenuated exercise-enhanced EF caused by repeated HIIE. [Methods] Eleven healthy men performed two sets of HIIE, and after each set, 30 min were given for rest and examination. In the 2^nd set, the subjects consumed experimental beverages containing (n = 6) and not containing (n = 5) lactate. Blood, cardiovascular, and psychological variables were measured, and EF was evaluated by the computerized color-word Stroop test. [Results] The lactate group had a higher EF (P < 0.05) and tended to have a higher blood lactate level (P = 0.082) than the control group in the 2^nd set of HIIE. Moreover, blood lactate concentration was correlated with the interference score (i.e., reverse score of EF) (r = -0.394; P < 0.05). [Conclusion] Our results suggest that the attenuated exercise-enhanced EF after repeated HIIE can be improved through lactate consumption. However, the role of lactate needs to be elucidated in future studies, as it can be used for improving athletes' performance and also in cognitive decline-related clinical studies.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.911-915
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• 2014

Aim: This study was to evaluate the effect of whole brain radiation (WBRT) combined with stereotactic radiotherapy (SRS) versus stereotactic radiotherapy alone for patients with brain metastases using a meta-analysis. Materials and Methods: We searched PubMed, EMBASE, Cochrane Library from their inception up to October 2013. Randomized controlled trials involving whole brain radiation combined with stereotactic radiotherapy versus stereotactic radiotherapy alone for brain metastases were included. Statistical analyses were performed using RevMan5.2 software. Results: Four randomized controlled trials including 903 patients were included. The meta-analysis showed statistically significant lowering of the local recurrence rate (OR=0.29, 95%CI: 0.17~0.49), new brain metastasis rate (OR=0.45, 95%CI: 0.28~0.71) and symptomatic late neurologic radiation toxicity rate (OR=3.92, 95%CI: 1.37~11.20) in the combined group. No statistically significant difference existed in the 1-year survival rate (OR=0.78, 95%CI: 0.60~1.03). Conclusions: The results indicate that whole brain radiotherapy combined with stereotactic radiotherapy has advantages in local recurrence and new brain metastasis rates, but stereotactic radiotherapy alone is associated with better neurological function. However, as the samples included were not large, more high-quality, large-sample size studies are necessary for confirmation.

• Journal of the Korean Data and Information Science Society
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• v.20 no.3
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• pp.541-550
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• 2009

This research attempted to find out any implications for strategies to design and develop the connections between the activities of the brain function and the fields of English learning (dictation, word level, speaking, word memory, listening). Thus, in developing the brain based learning model for the English education, attempts need to be made to help learners to keep the whole brain toward learning. On this point, this study indicated the significant results for the exclusive brain location and the brainwaves on the each English learning field by the quantitative EEG analysis. The results of this study presented the guidelines for the balanced development of the left brain and the right brain to train the specific site of the brain connected to the English learning fields. In addition, whole brain training model is developed by the quantitative EEG data not by the theoretical learning methods focused on the right brain training.