• Clinical and Experimental Emergency Medicine
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• v.5 no.4
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• pp.211-218
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• 2018

Objective This study aimed to determine whether simultaneous decreases in the serum levels of cell adhesion molecules (intracellular cell adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1], and E-selectin) and S100 proteins within the first 24 hours after the return of spontaneous circulation were associated with good neurological outcomes in cardiac arrest survivors. Methods This retrospective observational study was based on prospectively collected data from a single emergency intensive care unit (ICU). Twenty-nine out-of-hospital cardiac arrest survivors who were admitted to the ICU for post-resuscitation care were enrolled. Blood samples were collected at 0 and 24 hours after ICU admission. According to the 6-month cerebral performance category (CPC) scale, the patients were divided into good (CPC 1 and 2, n=12) and poor (CPC 3 to 5, n=17) outcome groups. Results No difference was observed between the two groups in terms of the serum levels of ICAM-1, VCAM-1, E-selectin, and S100 at 0 and 24 hours. A simultaneous decrease in the serum levels of VCAM-1 and S100 as well as E-selectin and S100 was associated with good neurological outcomes. When other variables were adjusted, a simultaneous decrease in the serum levels of VCAM-1 and S100 was independently associated with good neurological outcomes (odds ratio, 9.285; 95% confidence interval, 1.073 to 80.318; P=0.043). Conclusion A simultaneous decrease in the serum levels of soluble VCAM-1 and S100 within the first 24 hours after the return of spontaneous circulation was associated with a good neurological outcome in out-of-hospital cardiac arrest survivors.

• Journal of Physiology & Pathology in Korean Medicine
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• v.33 no.6
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• pp.356-362
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• 2019

Scutellaria baicalensis (SB) has widely used in the treatment for various brain diseases in the field of Oriental medicine. Biofermantation of SB can make major chemical constituents of SB to pass blood-brain barrier easily and to have more potent anti-oxidant ability. There is a little information about the contribution of fermented SB (FSB) to the formation or maintenance of the neural plasticity in the hippocampus. The purpose of this study was to evaluate effects of FSB extract on hydrogen peroxide (H₂O₂) - induced impairments of the induction and maintenance of long-term potentiation (LTP), an electrophysiological marker for the neural plasticity in the hippocampus. From hippocampal slices of rats, the field excitatory postsynaptic potentials (fEPSPs) were evoked by the electrical stimulation to the Schaffer collaterals - commissural fibers in the CA1 areas and LTP by theta-burst stimulation by using 64 - channels in vitro multi-extracellular recording system. In order to induce oxidative stress to hippocampal slices two different concentrations (200, 400 μM) of H₂O₂ were given to the perfused aCSF before and after the LTP induction, respectively. The ethanol extract of FBS with concentration of 25 ㎍/ml, 50 ㎍/ml was diluted in perfused aCSF that had 200 μM H₂O₂, respectively. Oxidative stress by the treatment of H₂O₂ resulted in decrease of the induction rate of LTP in the CA1 area with a dose - dependent manner. However, the ethanol extract of FSB prevented the reduction of the induction rate of LTP caused by H₂O₂ - induced oxidative stress with a dose - dependent manner. These results may support a potential application of FSB to ameliorate impairments of hippocampal dependent neural plasticity or memory caused by oxidative stress.

• Journal of Korean Neurosurgical Society
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• v.42 no.1
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• pp.27-34
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• 2007

Objective : On the magnetic resonance image (MRI) of the infiltrating brain tumor, enhancement is usually higher in malignant tumor than in benign tumor, and tumor cells can invade into the peritumoral area without definite enhancement. In various pathological conditions, the blood brain barrier (BBB) becomes changed to pathological condition, allowing various materials extravasating into the interstitial space, and degree of enhancement is depend on the pathology. Authors performed dynamic MRI on enhancing and surrounding edematous area in order to evaluate the degrees of opening of BBB, to differentiate tumor from non-tumorous condition, and to determine its relationship with the recurrence of the tumor. Methods : Dynamic MRI was performed in 25 patients. Dynamic scans were done every 15 seconds after administration of Gd-DTPA on the enhancing and surrounding area for maximum 300 seconds, and the patterns of enhancement were ana lysed. The enhancement curve with initial steep increase followed by slow decrease was defined as "N pattern", those with initial steep increase followed by additional slow increase as "T pattern", and those with initial steep increase followed by plateau as "E pattern". Histopathological findings were compared with the dynamic scan. Results : The graphs taken from enhancing area showed "T pattern" regardless of pathology. In the surrounding area, "T pattern" was noticed in the malignant tumors, but "E pattern" or "N pattern" was noted in low-grade or benign tumors and non-tumorous condition. "T pattern" in the surrounding area was related to the malignant with tumor cell infiltration and recurrence. Conclusion : The results suggest that the malignant tumor infiltration changes the condition of BBB enough to extravasate the Gd-DTPA. Enhancement pattern in the surrounding edematous area may be a useful information to differentiate the malignant glioma with the low-grade and benign tumors or other non-tumorous conditions.

• Journal of Life Science
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• v.28 no.11
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• pp.1386-1395
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• 2018

Over recent years, it has become evident that the central nervous system bidirectionally interacts with the gastrointestinal tract along the gut-brain axis. A series of preclinical studies indicate that the gut microbiota can modulate central nervous system function through a multitude of physiological functions. Polyphenols are ubiquitous plant chemicals included in foods such as fruits, vegetables, tea, coffee and wine, and their consumption is directly responsible for beneficial health effects due to antioxidant, anti-inflammatory, antimicrobial, immunomodulatory, anticancer, vasodilating, and prebiotic-like effects. There is increasing evidence that dietary polyphenol can contribute to beneficial effects in neuronal protection acting against oxidative stress and inflammatory injury as well as in cognitive functions. In this paper, we overview the neuroprotective role of dietary polyphenols especially focusing on the neuroinflammation and neurovascular function by interaction with the gut microbiome. Polyphenol metabolites could directly act as neurotransmitters crossing the blood-brain barrier and modulating the cerebrovascular system or indirectly modulating gut microbiota. In addition, evidence suggests that dietary polyphenols are effective in preventing and managing neurological disorders, such as age-related cognitive decline and neurodegeneration, through a multitude of physiological functions. Dietary polyphenols are increasingly envisaged as a potential nutraceuticals in the prevention and treatment of neurological disorders, because they possess the ability to reduce neuroinflammation, to improve memory and cognitive function and to modulate the gut microbiota.

• The Korean Journal of Nuclear Medicine
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• v.34 no.5
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• pp.371-380
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• 2000

Purpose: Thallim-201 ($^{201}Tl$) brain SPECT, which can represent cellular activity of brain lesions, may provide more useful information in differentiating between benign and malignant brain lesions more so than CT of MRI, that merely represents anatomic changes or breakdown of blood brain barrier. We used $^{201}Tl$ brain SPECT prospectively to evaluate the utility of $^{201}Tl$-indices as an indicator of benign or malig nant lesions. Materials and Methods: We studied 28 patients. There were 13 cases of benign lesions (3: nonspecific benign lesion, 3: meningioma, 2: low grade glioma, 1: tuberculoma, central neurocytoma, hemangioblastoma, radiation necrosis, and choroid plexus papilloma) and 15 cases of malignant lesions (6: glioblastoma multiforme, 5: anaplastic glioma, 2: medulloblastoma, 1: metastasis and lymphoma). In all patients, CT and/or MRI were obtained and then $^{201}Tl$ brain SPECT was obtained with measuring mean $^{201}Tl$ index and peak $^{201}Tl$ index. An unpaired t-test was performed to compare the $^{201}Tl$-indices and pathologic diagnoses to evaluate the utility of $^{201}Tl$-indices as all indicator of benign or malignant lesions. Results: There were no statistically significant difference in $^{201}Tl$-indices between benign and malignant brain lesion (p>0.05). Conclusion: These results demonstrated that we could not use $^{201}Tl$ indices on brain SPECT alone as an indicator of benign or malignant brain lesions.

• The Journal of Internal Korean Medicine
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• v.25 no.3
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• pp.461-472
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• 2004

Objectives : For the screening of neuroprotective effects of medicinal herbs, the complex system of animal models suffer some disadvantages in controlling critical parameters such as blood pressure and body temperature. Additionally, application of drugs to the appropriate brain area sometimes is difficult, due to poor permeability though the blood brain barrier, and so potential protective effects might be masked. Methods : Organotypic hippocampal slice culture (OHSC) method has the advantages of being relatively easy to prepare and of maintaining the general structure, including tissue integrity and the connections between cells. Drugs can easily be applied and neuronal damage can easily be quantified by using tissues and culture media. This study demonstrates neuroprotective effects of Puerariae radix (葛根, PR), Salviae miltiorrhizae radix (丹蔘, SR), Rhei rhizoma (大黃, RR), and Bupleuri radix (柴胡, BR). These were screenedand compared to MK-801, antagonist of NMDA receptors, by using OHSC of 1 week-old Sprague-Dawley rats. Oxygen/glucose deprivation (OGD) were conducted in an anaerobic chamber $(85%\;N_2,\;10%\;CO_2\;and\;5%\;H_2)$ in a deoxygenated glucose-free medium for 60 minutes. Water extracts of each herbs were treated to culture media with $5\;{\mu}g/ml$ for 48 hours. Results : Neuronal cell death in the cultures was monitored by densitometric measurements of the cellular uptake of propidium iodide (PI). PI fluorescence images were obtained at 48 hours after the OGD and medicinal herb treatment. Also TUNEL-positive cells in the CAI and DG regions and LDH concentrations in culture media were measured at 48 hours after the OGD. According to measured data, MK-801, PR, SR and BR demonstrated significant neuroprotective effect against excessive neuronal cell death and apoptosis induced by the OGD insult. Especially, PR revealed similar neuroprotective effect to MK-801 and RR demonstrated weak neuroprotective effect. Conclusions : These results suggest that OHSC can be a suitable method for screening of neuroprotective effects of medicinal herbs. (This work was supported by the research program of Dongguk University and Grant 01-PJ9-PG1-01CO03-0003 from Ministry of Health & Welfare.)

• Maxillofacial Plastic and Reconstructive Surgery
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• v.31 no.5
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• pp.365-374
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• 2009

Purpose : This research evaluates the effect of the use of absorbable membrane barrier with deproteinized bovine bone (Bio-$Oss^{(R)}$, Switzerland) on bone healing in surgically created critical-sized defects in rat calvaria. Materials and Methods : Two standardized transosseous circular calvarial defects (5 mm in diameter) are made in each calvarium of 30 rats. These rats are divided into negative control group(n=15), positive control group(n=15) and two experimental groups(n=15). In the negative control group, defects are only filled with blood clots. In the positive control group, defects are filled with autogenous bone obtained from calvarium; in the experimental group 1, defects are filled with deproteinized bovine bone; and in the experimental group 2, defects are filled with deproteinized bovine bone with absorbable membrane. At the postoperative 1 week, 3 weeks. and 6 weeks, clinical. histologic and histomorphometric evaluations of the defects are performed. Results : 1. The grafted bone without membrane in the calvarial bone defect was scattered but, the grafted bone with membrane was stable. 2. $BioMesh^{(R)}$ membrane was absorbed beginning at 3 weeks, and was absorbed considerably at 6 weeks while maintaining the structural form of the membrane. 3. The use of membrane blocked soft tissue invasion. 4. In histomorphometric analysis. it showed the greatest amount of new bone formation in the positive control group. The amount of new bone formation was greater in the experimental group 2 than experimental group 1. At 6 weeks. the amount of new bone formation was greater in the positive control group than experimental group l(p<0.005). Conclusion : These results suggest that membrane increase the stability of grafted bone and protects from soft tissue invasion, and the use of the membrane may promote new bone formation in deproteinized bovine bone graft area.

• Clinical and Experimental Pediatrics
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• v.46 no.6
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• pp.548-553
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• 2003

Purpose : Matrix metalloproteinase(MMP)-9 is known to breakdown the blood-brain barrier by degrading the extracellular matrix of the subendothelial basement membrane in meningitis. Tissue inhibitor of metalloproteinase(TIMP)-1, a known inhibitor of MMP-9, has been postulated to inhibit the proteolytic activity of MMP-9 by bindng to MMP-9, but their interaction has not been fully understood yet. So far, there have been some reports on the relationship of MMP-9 and TIMP-1 in bacterial meningitis, but few reports in viral meningitis. Furthermore, there has been no report on this in Korea. We investigated the concentrations of MMP-9 and TIMP-1 in cerebrospinal fluid (CSF) and serum of patients with viral meningitis and control subjects, and evaluated their relationship with other clinical parameters of meningitis. Methods : CSF and blood were obtained from 25 subjects with viral meningitis and 14 control subjects. After centrifugation, supernatants were stored at $-20^{\circ}C$ and we assayed concentrations of MMP-9 and TIMP-1 by the sandwich ELISA method. Results : Concentrations of CSF MMP-9 and TIMP-1 were significantly elevated in patients with viral meningitis, when compared with those in control subjects. Their serum levels showed no differences between the two groups. MMP-9 levels were closely correlated with TIMP-1 levels in the CSF($r_s=0.42$, P<0.05). CSF MMP-9/TIMP-1 ratios were significantly higher in patients with viral meningitis than those in the control subjects(P<0.05). Both CSF MMP-9 and TIMP-1 levels positively correlated with CSF total leukocyte counts($r_s=0.43$, P<0.05, $r_s=0.48$, P<0.05). TIMP-1 levels positively correlated with total protein concentrations in the CSF($r_s=0.43$, P<0.05). Conclusion : MMP-9 and TIMP-1 may play an important role in the breakdown and maintenance of BBB in viral meningitis, respectively.

• Molecules and Cells
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• v.40 no.2
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• pp.133-142
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• 2017

Previous studies have shown that bone marrow mesenchymal stromal cell (MSC) transplantation significantly improves the recovery of neurological function in a rat model of intracerebral hemorrhage. Potential repair mechanisms involve anti-inflammation, anti-apoptosis and angiogenesis. However, few studies have focused on the effects of MSCs on inducible nitric oxide synthase (iNOS) expression and subsequent peroxynitrite formation after hypertensive intracerebral hemorrhage (HICH). In this study, MSCs were transplanted intracerebrally into rats 6 hours after HICH. The modified neurological severity score and the modified limb placing test were used to measure behavioral outcomes. Blood-brain barrier disruption and neuronal loss were measured by zonula occludens-1 (ZO-1) and neuronal nucleus (NeuN) expression, respectively. Concomitant edema formation was evaluated by H&E staining and brain water content. The effect of MSCs treatment on neuroinflammation was analyzed by immunohistochemical analysis or polymerase chain reaction of CD68, Iba1, iNOS expression and subsequent peroxynitrite formation, and by an enzyme-linked immunosorbent assay of pro-inflammatory factors (IL-$1{\beta}$ and TNF-${\alpha}$). The MSCs-treated HICH group showed better performance on behavioral scores and lower brain water content compared to controls. Moreover, the MSC injection increased NeuN and ZO-1 expression measured by immunochemistry/immunofluorescence. Furthermore, MSCs reduced not only levels of CD68, Iba1 and pro-inflammatory factors, but it also inhibited iNOS expression and peroxynitrite formation in perihematomal regions. The results suggest that intracerebral administration of MSCs accelerates neurological function recovery in HICH rats. This may result from the ability of MSCs to suppress inflammation, at least in part, by inhibiting iNOS expression and subsequent peroxynitrite formation.

• Applied Microscopy
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• v.18 no.2
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• pp.177-186
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• 1988

Degeneration of the axon terminals of mamillo-thalamic tract following the electrical coagulation of mamillary body is well known. In this study, the author investigated the ultrastructural alterations of neuropil components, initiated by terminal degenerations. Rats weighing approximately 250 gm were fixed on the stereotaxic instrument(David Kopf Inc., Heavy duty model), and NE 300 active electrode(Rhodes Med. Instr. Inc.) was introduced to the mamillary position of anterior 3.8 mm, lateral 0.5 mm, height 3.8 mm and lateral angle of $23^{\circ}$ according to De Groot's Atlas. Electric current of 20 mA was applied during 1 minute between active and inactive electrodes with Radio Frequency Lesion Generator(RFG 4, Radionics Inc.). Two hours, 2 days, 1 week and 2 weeks following the electrical coagulation of mamillary body, ipsilateral anterior thalamic nucleus was fixed in 1% glutaraldehyde-l% paraformaldehyde and 2% osmium tetroxide, embedded in Araldite mixture, cutted with LKB ultra tome V, stained with uranyl acetate-lead citrate and observed with JEOL 100 CX electron microscope. Observed results were as follows; 1. Degenerated mamillo-thalamic synapses were observed to form asymmetric axospinous or axo-dendritic types. 2. Terminal degeneration was not easily discernible at 2 hours interval after mamillary lesion, but following 2 days the terminal degeneration was apparent. 3. Postsynaptic spines, dendrites and even their cell bodies show edematic changes caused by the degeneration of postsynaptic counterpart. 4. Astrocytic territories, including perivascular processes forming glial limitans of blood-brain barrier, exhibit remarkable expansion. 5. Oligoglia and astroglia are actively engaged in the removal of degenerated elements. 6. Active forms of microglia were increased. 7. The observed results may represent typical ultrastructural alteration pattern within neuropil following the degeneration of certain input axon terminals.