• Biomolecules & Therapeutics
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• v.8 no.3
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• pp.255-261
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• 2000

WooHwangChungSimWon is a traditional prescription for treating with hypertension, arteriosclerosis, coma, and stroke in China, Korea, and Japan. In the new presciption of WooHwangChungSimWon, the covet is substituted for the musk, the major component of WooHwangChungSimwon, because of the prohibition law about the musk. We have made a comparative study of the effects on the ischemic damage between the musk containing and civet containing WooHwangChungSimWon. In order to investigate the effects of WooHwangChungSimWon on the ischemic damage, each samples were administrated for 12 days, ischemia was induced for 10 minutes at 7th day, and immunohistochemistry was performed in the region of hippocampus of mongolian gerbils. According to the result of immunohistochemistry, the survival rates of neuroal cells in the hippocampal CA1 region are 37.8% in the high dose of musk containing WooHwangChungSimWon (HM-WHCSW) administrated group, 27.8% in low dose of civet containing WooHwangChungSimWon (LC-WHCSW), and 35.5% in high dose of civet containing WooHwangChungSimWon (HC-WHCSW) administrated group. These survial rates were significantly different from the survival rate of sham control group (14.4%). The results suggest that all the samples except the low dose of musk containing WooHwangChungSimWon (LM-WHCSW) have protective or preventive effects on cerebral ischemia.

• Journal of Chest Surgery
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• v.34 no.7
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• pp.547-551
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• 2001

The effects of deep hypothermia and circulatory arrest during aortic arch reconstruction are associated with potential neurologic and myocardial injury. We describe a surgical technique that two patients underwent a modified Norwood procedure without circulatory arrest and myocardial ischemia. One was 13-day-old female patient, weighing 3.1kg, having a variant of hypoplastic left heart syndrome and another was 38-day-old male patient, weighing 3.4 kg, diagnosed Taussig-Bing anomaly with severe aortic arch hypoplasia, coarctation of the aorta, and subaortic stenosis. The arterial cannula was inserted in innominate artery directly. During Norwood reconstruction, regional high-flow perfusion into the inominate artery and coronary perfusion were maintained and there were no neurologic, cardiac, and renal complications in two patients. This technique may help protect the brain and myocardium from ischemic injury in patients with hypoplastic left heart syndrome or other arch anomalies including coarctation or interruption.

• Neonatal Medicine
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• v.16 no.2
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• pp.221-233
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• 2009

Purpose: Erythropoietin (EPO) has neuroprotective effects in many animal models of brain injury, including hypoxic-ischemic (HI) encephalopathy, trauma, and excitotoxicity. Current studies have demonstrated the neuroprotective effects of EPO, but limited data are available for the neonatal periods. Here in we investigated whether recombinant human EPO (rHuEPO) can protect the developing rat brain from HI injury via modulation of NMDA receptors. Methods: In an in vitro model, embryonic cortical neuronal cell cultures from Sprague-Dawley (SD) rats at 19-days gestation were established. The cultured cells were divided into five groups: normoxia (N), hypoxia (H), and 1, 10, and 100 IU/mL rHuEPO-treated (H+E1, H+ E10, and H+E100) groups. To estimate cell viability and growth, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was done. In an in vivo model, left carotid artery ligation was performed on 7-day-old SD rat pups. The animals were divided into six groups; normoxia control (NC), normoxia Sham-operated (NS), hypoxia-ischemia only (H), hypoxia-ischemia+vehicle (HV), hypoxia-ischemia+rHuEPO before a HI injury (HE-B), and hypoxia-ischemia+rHuEPO after a HI injury (HE-A). The morphologic changes following brain injuries were noted using hematoxylin and eosin (H/E) staining. Real-time PCR using primers of subunits of NMDA receptors (NR1, NR2A, NR2B, NR2C and NR2D) mRNA were performed. Results: Cell viability in the H group was decreased to less than 60% of that in the N group. In the H+E1 and H+E10 groups, cell viability was increased to >80% of the N group, but cell viability in the H+E100 group did not recover. The percentage of the left hemisphere area compared the to the right hemisphere area were 98.9% in the NC group, 99.1% in the NS group, 57.1% in the H group, 57.0% in the HV group, 87.6% in the HE-B group, and 91.6% in the HE-A group. Real-time PCR analysis of the expressions of subunits of NMDA receptors mRNAs in the in vitro and in vivo neonatal HI brain injuries generally revealed that the expression in the H group was decreased compared to the N group and the expressions in the rHuEPO-treated groups was increased compared to the H group. Conclusion: rHuEPO has neuroprotective property in perinatal HI brain injury via modulation of N-methyl-D-aspartate receptors.

• Journal of Korean Biological Nursing Science
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• v.4 no.2
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• pp.19-40
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• 2002

The purpose of this study was to determine the effect of DHEA on Type I(soleus) and II muscles(plantaris, gastrocnemius) in a focal brain ischemia model rat. Thirty-seven male Sprague-Dawley rats with $200{\sim}250g$ body weights were randomly divided into four groups : CINS(cerebral ischemia + normal saline), CIDH(cerebral ischemia + DHEA), SHNS(sham + normal saline), SHDH (sham + DHEA). Both the CINS and CIDH groups were undergone a transient right middle cerebral artery occlusion operation. In the SHNS and SHDH groups, a sham operation was done. DHEA was administered daily at a dose of 0.34mmol/kg, and normal saline was administered daily at the same dose by intraperitoneal injection for 7days after operation. Cerebral infarction in the CINS and CIDH groups was identified by staining with 2% triphenyltetrazolium chloride solution for 60 minutes. The data were analyzed by Kruskal-Wallis test and Mann-Whitney U test using the SPSSWIN 9.0 program. The results were summarized as follows: 1) The muscle weights of soleus(Type I), plantaris and gastrocnemius(Type II) in CINS group were significantly less than those of the SHNS group(p<.01). The muscle fiber cross-sectional area of the CINS group was significantly less than that of the SHNS group in Type I muscle fiber of the soleus and Type II muscle fiber of the plantaris and gastrocnemius(p<.05). The myofibrillar protein content of the CINS group was significantly less than that of the SHNS group in the left gastrocnemius and right soleus(p<.05). 2) The muscle weights of the soleus, plantaris and gastrocnemius except the unaffected side of the plantaris in the CIDH significantly increased compared to those of the CINS group(p<.05). The muscle fiber cross-sectional area of the CIDH group significantly increased compared to that of the CINS group in Type II muscle fiber of the plantaris and gastrocnemius(p<.05). The myofibrillar protein content of the CIDH group significantly increased compared to that of the CINS group in the left soleus(p<.05). 3) On the post-op 8 day, the body weight of the CINS group was significantly less than that of the CIDH, SHNS and SHDH groups(p<.01). Total diet intake of the CINS and CIDH groups was significantly less than that of the SHNS and SHDH groups(p<.01). Based on these results, it was identified that muscle atrophy could be induced during the 7 days after cerebral infarction, and DHEA administration during the early stage of cerebral infarction might attenuate muscle atrophy.

• Clinical and Experimental Pediatrics
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• v.48 no.5
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• pp.545-550
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• 2005

Purpose : Newborn brain tissue has to be dissociated into a single cell suspension for flow cytometric analysis of cell death during hypoxia-ischemia. Thus the development of a method to dissociate cells from the brain tissue with least damage and maintenance of membrane and antigen integrity remains the challenge for the in vivo application of this technique. We evaluated the efficacy of mechanical or enzymatic (collagenase or tryspin) methods of brain tissue disaggregation. Methods : The extent of the damage to the plasma membrane and loss of the characteristics of the membrane induced with each dissociation method was determined by comparing the flow cytometric results labeled with both fluorescent annexin V and propidium iodide of the newborn rat pup brain tissue in the control group (n=10) and in the 48-hour after hypoxia-ischemia group (n=10). Results : In the control group, the cell percentage of damaged, apoptotic and necrotic cells of both hemispheres with the mechanical dissociation method was significantly increased compared to the trypsin or collagenase method. In the 48-hour after hypoxia-ischemia group, the cell percentage of apoptotic and necrotic cells of the right hemisphere with the collagenase method significantly increased, and live cells significantly decreased compared to the left hemisphere, control group. Although the same trend was observed, the extent of alterations made with the trypsin method was significantly less compared to the collagenase method. Conclusion : The dissociation of neonatal brain tissue for flow cytometric analysis with collagenase was most efficacious with the least cell damage and preservation of the plasma membrane characteristics.

• The Korean Journal of Nuclear Medicine
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• v.30 no.4
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• pp.484-492
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• 1996

To detect ischemic tissue in experimental model of cerebral ischemia made by middle cerebral artery(MCA)-occlusion, we acquired triple image of $^{99m}Tc$-glucarate, [$^{18}F$]fluoro-deoxyglucose (FDG), and 2,3,5- triphenyltetrazolium (TTC) staining. We made cerebral infarction either with reperfusion (after occlusion of 2 hours) or without reperfusion in 10 Sprague-Dawley rats by inserting thread to MCA through internal carotid artery. After 22 hours, we injected 740 MBq of $^{99m}Tc$-glucarate and 55.5 MBq of [$^{18}F$]FDG through tail vein. Each 1 mm slice of rat brains was frozen and exposed to imaging plate for 20 minutes in freezer to get an [$^{18}F$]FDG image. After 20 hours enough to fade radioactivity of [$^{18}F$]FDG, the slices were again imaged by BAS1500 for $^{99m}Tc$-glucarate uptake. Finally, these brain tissues were stained with TTC. Semi-quantitative visual analysis was done by grading 0 to 3 points according to the degree of uptakes($^{99m}Tc$-glucarate) and decreased uptakes([$^{18}F$]FDG and TTC). Ten rats survived with neurologic symptoms. TTC staining confirmed the development of infarction. The size of the infarction was relatively larger in the group without reperfusion. [$^{18}F$]FDG images were similar to TTC-stained images. However, we found regions with intermediate uptake which were not stained with TTC. We found regions with intermediate [$^{18}F$]FDG uptake where TTC staining was normal. $^{99m}Tc$-glucarate uptake was round only in TTC non-stained region. In the TTC stained regions, there were no uptake of $^{99m}Tc$-glucarate. We could not find clear relation between $^{99m}Tc$-glucarate uptake with [$^{18}F$]FDG uptake. This was partly because percent uptake of $^{99m}Tc$-glucarate was so small (less than 1 percent of injected dose) and because there were quite heterogeneity of patterns of [$^{18}F$]FDG uptake and TTC. With these findings, we could conclude that $^{99m}Tc$-glucarate were taken up only in part of ischemic tissues which were proven to be nonviable. The establishment of MCA-occluded rat model with or without reperfusion and triple imaging for $^{99m}Tc,\;^{18}F$ and TTC helped the characterization of $^{99m}Tc$-glucarate uptakes. Further work is needed to clarify the meaning or diversities or [$^{18}F$]FDG and TTC and their relation with $^{99m}Tc$-glucarate.

• Progress in Medical Physics
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• v.18 no.3
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• pp.149-160
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• 2007

Recent advent of 64-multidetctor (MD) CT enables more coverage of Z-axis in the perfusion imaging. The purpose of this study was to evaluate the clinical usefulness of perfusion CT by using 64-MD CT in detecting the lesion in patients with acute stroke. The perfusion CT was performed by using 64-MD CT in 62 consecutive patients who were initially suspected to have subacute ischemic stroke symptoms during the period of recent 9 months. These patients had subacute stroke (n=62). CT scanning was conducted with Jog Mode which provided 16 imaging slices with 5 mm of slice thickness, and 8 cm of coverage in Z-axis. Scan interval was 1 seconds for each imaging slice and total 15 scans were repeated. After CT scanning, perfusion maps (CBV, CBF, MTT and TTP) were created at Extended Brilliance Workstation. The CBV and CBF maps showed that lesions were smaller images. While on the MTT and TTP map lesions were seen to be larger fifty-one were large than they appeared on these images. Two slices of perfusion maps obtained at the level of the basal ganglia were chosen to simulate conventional older perfusion CT with 8 cm of coverage in Z-axis. TTP and MTT maps may be clinically useful for evaluation of the penumbral zone in cases of aubacute cerebral ischemic stroke. The perfusion CT is useful in the assessment of acute stroke as an initial imaging modality.

• 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 Acupuncture Research
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• v.20 no.4
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• pp.85-92
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• 2003

목적 : 허혈시 발생되는 저산소중 상태에서는 세포독성을 유발한다고 알려져 있으나 정확한 기전은 아직 규명되지 않았다. 본 연구에서는 뇌허혈로 인한 세포독성의 기전을 유전자 발현을 통하여 살펴보고자 하였다. 방법 : 본 실험에서는 BV-2 microglia 세포주에 12시간 동안의 저산소 상태에서의 유전자 발현을 분석하기 위하여 마이크로에레이를 시행하였다. 결과 : 저산소 상태에서는 정상에 비하여 cathepsin F, growth factor independent 1, calcitonin/calcitonin-related poly, leucine-rich repeat LGI family membrane, dublecortin, cyclohydrolase 1, Ia-associated invariant chain, carbohydrate kinase-like과 erythrocyte protein band 4.1-like 3 등의 유전자 발현이 3배 이상 증가하였다. 한편 neuronal guanine nucleotide exchange factor, Bcl-2-related ovarian killer protein, chemokine (C-X-C motif) ligand 5, RNA binding motif protein 3, interleukin 2 receptor, alpha chain, crystallin zeta, cytochrome P450 subfamily IV B, asparagine synthetase과 moesin 등의 유전자 발현은 0.2배 이하로 감소하였다. 결론 : 이상의 결과는 저산소중에 관여하는 유전자 및 저산소중과 관련된 뇌경색 등의 질환의 기전을 밝히는데 기초적 자료로 이용될 수 있을 것이다.

• The Korean Journal of Pharmacology
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• v.32 no.3
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• pp.323-334
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• 1996

Male Mongolian gerbils $(60{\sim}80g)$ were given DL-difluoromethylornithine (DFMO; 250mg/kg, ip) and methylglyoxal bis(guanylhydrazone) (MGBG; 50 mg/k, ip), respectively, 1 h prior to transient (7 min) occlusion of bilateral common carotid arteries (OBC7) and a daily dose of one of them for 6 days after recirculation, and the polyamine contents, activities of ornithine and S-adenosylmethionine decarboxylases (ODC and SAM-DC), and light microscopic findings of the hippocampus were evaluated. The hippocampal putrescine (PT) levels of the control gerbils treated with saline (STGr), markedly increased after OBC7, showing a peak level at 24 h after recirculation. The peak PT level was reduced in DFMO treated gerbils (DTCr) and in MGBG treated gerbils (MTGr). And 7 days after recirculation, the PT level of DTGr was decreased to about 75% of the PT level in the sham operated group (nonTGr) and to about 55% of the STGr level, respectively. The hippocampal spermidine (SD) level of STGr tended to decline, showing the lowest value at 8 h after recirculation. But the spermidine (SD) level of DTGr was somewhat higher at 8 h after OBC7 than those of STGr and MTGr The hippocampal spermine (SM) levels of all the experimental groups were little changed for 7 days after OBC. OBC7 markedly increased the hippocampal ODC activity. reaching a maximum (about 3 times higher than preischemic level) at 8 h and rapidly recovered to the control value by 24 h in STGr gerbils, and the OBC7-induced increase of ODC activity was significantly attenuated by DFMO or MGBG treatment. Whereas OBC7 induced a rapid decrease of the hippocampal SAMDC activity follwed by gradual recovery to the preischemic level, and the decrease of the SAMDC activity was slightly attenuated by DFMO or MGBG treatment. 7 Days after OBC7 the histological finding of the hippocampal complex stained with cresyl violet showed an extensive delayed neuronal damage in the CA1 region and to a lesser extent, in the dentate gyrus, sparing the CA3 region. And the neuronal death was aggevated by DFMO but significantly attenuated by MGBG. The immunochemical reactivity of hippocampus to anti-GFAP antibody was significantly increased in the CA1 region and to a lesser extent, in the dentate gyrus 7 days after OBC7, but was little changed in the CA3. And the increase of the anti-GFAP immunoreactivity was moderately enhanced by DFMO and significantly suppressed by MGBG. These results suggest that the polyamine metabolism may play a modulatory role in the ischemic brain damage.