• Title/Summary/Keyword: Cerebral protection

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Protective role of Populus tomentiglandulosa against hydrogen peroxide-induced oxidative stress in SH-SY5Y neuronal cells

  • Kwon, Yu Ri;Kim, Ji Hyun;Lee, Sanghyun;Cho, Eun Ju;Kim, Hyun Young
    • Journal of Applied Biological Chemistry
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    • v.63 no.4
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    • pp.357-363
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    • 2020
  • Oxidative stress caused by the overproduction of reactive oxygen species (ROS) is known as an etiology of neurodegenerative diseases. Populus tomentiglandulosa (PT), a member of the Salicaceae family, is widely grown in Korea and has been reported to exert protective effects on cerebral ischemia by attenuating of oxidative stress and neuronal damage. In the present study, we investigated the antioxidant activity and neuroprotective effects of an ethanol extract and four fractions [n-butanol, ethyl acetate (EtOAc), chloroform, and n-hexane] of PT under in vitro and cellular systems. The extract and four fractions of PT showed 1,1-diphenyl-2-picrylhydrazyl (DPPH), •OH, and O2- radical scavenging activities in a dose-dependent manner. In particular, the EtOAc fraction of PT had the strongest DPPH, •OH, and O2- radical scavenging activities among the extract and other fractions. Therefore, we further investigated the neuroprotective effect of the EtOAc fraction of PT against oxidative stress in H2O2-induced SH-SY5Y cells. Treatment with H2O2 significantly decreased cell viability and lactate dehydrogenase (LDH) release, and it also increased the ROS levels compared to the normal group. However, treatment with the EtOAc fraction of PT significantly increased cell viability. Moreover, the EtOAc fraction of PT-treated group significantly suppressed ROS production and LDH release compared to the H2O2-induced control group. In conclusion, our findings indicated that PT had in vitro antioxidant activity and neuroprotective effects against oxidative stress. Therefore, PT could be used as a natural agent for protection against oxidative stress.

Study on the Protective Effect of Nelumbo nucifera GAERTN Extract on Cultured Cerebral Neuroglial Cells Damaged by Hexavalent Chromium (연꽃추출물이 6가 크롬으로 유도된 세포독성에 대한 보호효과에 관한 연구)

  • Seo, Young-Mi;Park, Yun-Jum;Choi, Yu-Sun
    • FLOWER RESEARCH JOURNAL
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    • v.17 no.4
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    • pp.242-245
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    • 2009
  • In order to investigate the cytotoxic effect of hexavalent chromium ($Cr0_3$) and the protective effect of Nelumbo nucifera GAERTN (NNG) extract, cultured cerebral neuroglial cells (C6 glioma cells) were treated with $4{\sim}55{\mu}M$ concentrations of $Cr0_3$ for 48 hours. Cell viability was measured by XTT assay. The superoxide dismutase (SOD)-like activity for the antioxidant effect was also examined on the extract of NNG stamen. In this study, $Cr0_3$ significantly decreased cell viability dose-dependently. The cytotoxicities of $XTT_{90}$ and $XTT_{50}$ determined with $10{\mu}M$ and $55{\mu}M$ of $Cr0_3$, respectively, showed that the $Cr0_3$ had highly toxic effect on cultured C6 glioma cells by the cytotoxic criteria. In the protective effect of NNG extract, the cell viability was significantly increased by the treatment of NNG extract, and NNG extract increased SOD-like activity. From these results, it is suggested that $Cr0_3$ showed highly toxic effect on cultured C6 glioma cell s and NNG extract was very effective in the protection of $Cr0_3$-mediated cytotoxicity by antioxidative effect in these cultures.

Molecular Characterization of Ischemia-Responsive Protein 94 (irp94) Response to Unfolded Protein Responses in the Neuron

  • Kim Seung-Whan;Kwon Ki-Sang;Shin Kee-Sun;Kim Seung-Ho;Kwon O-Yu
    • Biomedical Science Letters
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    • v.12 no.2
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    • pp.81-89
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    • 2006
  • The ischemia-responsive 94 gene (irp94) encoding a 94 kDa endoplasmic reticulum resident protein was investigated its molecular properties associated with unfoled protein responses. First, the expression of irp94 mRNA was tested after the reperfusion of the transient forebrain ischemia induction at the central nervous system in three Mongolian gerbils. Second, irp94 expression in PC12 cells, which are derived from transplantable rat pheochromocytoma cultured in the DMEM media, was tested at transcriptional and translational levels. The half life of irp94 mRNA was also determined In PC12 cells. Last, the changes of irp94 mRNA expression were investigated by the addition of various ER stress inducible chemicals (A23187, BFA, tunicamycin, DTT and $H_2O_2$) and proteasome inhibitors, and heat shock. High level expression of irp94 mRNA was detected after 3 hours reperfusion in the both sites of the cerebral cortex and hippocampus of the gerbil brain. The main regulation of irp94 mRNA expression in PC 12 cells was determined at the transcriptional level. The half life of irp94 mRNA in PC12 cells was approximately 5 hours after the initial translation. The remarkable expression of irp94 mRNA was detected by the treatment of tunicamycin, which blocks glycosylation of newly synthesized polypeptides, and $H_2O_2$, which induces apoptosis. When PC12 cells were treated with the cytosol proteasome inhibitors such as ALLN (N-acetyl-leucyl-norleucinal) and MG 132 (methylguanidine), irp94 mRNA expression was increased. These results indicate that expression of irp94 was induced by ER stress including oxidation condition and glycosylation blocking in proteins. Expression of irp94 was increased when the cells were chased after heat shock, suggesting that irp94 may be involved in recovery rather than protection against ER stresses. In addition, irp94 expression was remarkably increased when cytosol proteasomes were inhibited by ALLN and MG 132, suggesting that irp94 plays an important role for maintaining the ERAD (endoplasmic reticulum associated degradation) function.

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Protective effects of Chungpesagan-tang against ischemia/reperfusion induced cell injury (허혈/재관류 세포 손상에서 청폐사간탕의 보호 효과)

  • Hong, Seong-Gil;Kang, Bong-Joo;Kim, Yun-JIn;Kang, Sang-Mo;Cho, Dong-Wuk
    • Korean Journal of Oriental Medicine
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    • v.5 no.1
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    • pp.111-117
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    • 1999
  • Free radicals are thought to be the most important cause of the reperfusion injury subsequent to ischemia. The antioxidant status of the tissue affected by ischemia-reperfusion is of great importance for the primary endogenous defense against the free radical induced injury. Therefore, antioxidant therapy has been shown to be beneficial in neurological disorders such as Alzheimer's disease and cerebral ischemia. In this study, the protective effects of Chungpesagan-tang (CST) was investigated against ischemia/reperfusion-induced cytotoxicity in SK-N-MC neuronal cells It was found out that low concentration of CST was highly effective in protecting neuronal cells against ischemia/reperfusion-induced cytotoxicity. The inhibitory effect of CST on malondialdehyde formation during ischemia/reperfusion-induced oxidative stress in SK-N-MC cells showed obvious dose-dependent responses. Also, CST showed relatively high inhibitory activity to xanthine oxidase induced by ischemia/reperfusion environment Therefore, it is thought that CST has both antioxidant and xanthine oxidase inhibitory effect and can be used for clinical applications for protection of neuronal cells from ischemia-reperfusion injury.

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The Effect of Dodamtang(DDT) on Brain damage and Hypertension (도담탕(導痰湯)이 뇌손상(腦損傷) 및 고혈압(高血壓)에 미치는 영향(影響))

  • Lim, Seong-Min;An, Joung-Jo;Choi, Young;Kim, Yong-Jin;Yoo, Ho-Ryoung;Park, Yang-Chun;Seol, In-Chan;Hwang, Chi-Won;Cho, Hyun-Kyung
    • The Journal of Internal Korean Medicine
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    • v.22 no.4
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    • pp.503-512
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    • 2001
  • Objective : This study was carried out to investigate the effects of DDT on the brain damage and hypertension. Methods : We observed the effect of Dodamtang(DDT) extract on KCN-induced coma, focal brain ischemia by MCA occlusion, cytotoxicity and protection of PC12 cells and B103 cells induced by amyloid ${\beta}$ protein(25-35). To prove the effect of DDT as a blood pressure depressant, we measured aldosterone, renin activity, catecholamine, sodium and NO density using the seperated blood plasma. Results : DDT showed a protective effect on cytotoxicity of PC12 cells and B103 cells induced by amyloid ${\beta}$ protein(25-35) in a dose dependent manner and proved the significant abridgement of brain ischemic area and edema induced by MCA occlusion, a critical decrease of neurologic deficitic grade in the fore-limbs. DDT didn't reduce the duration of KCN(1.87mg/kg iv.)-induced coma and prolonged the survival rate in the case of KCN(3.0mg/kg iv.)-induced coma by the ratio of 20%. While DDT increased the value of NO in SHR, it significantly decreased the blood pressure of SHR and the value of aldosterone& epinephrine in SHR. Conclusions : These results suggested that DDT might be usefully applied for treatment of hypertension, cerebral infarction, and brain damage.

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Risk Factors of Morbidity and Mortality after Coronary Artery Bypass Grafting (관상동맥우회로 이식술 후 이환과 사망의 위험요인)

  • 박창률;이응배;전상훈;장봉현;이종태;김규태
    • Journal of Chest Surgery
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    • v.31 no.12
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    • pp.1159-1164
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    • 1998
  • Background: Although operative outcome is progressing due to the development of operative techniques and myocardial protection, some patients face an increased morbidity and mortality. Therefore, it has become increasingly important to predict the operative morbidity and mortality. Material and Method: This retrospective study reports the results of risk factor analysis of morbidity and mortality of 137 consecutive patients who were underwent coronary artery bypass graft surgery(CABG). Preoperative variables were age, sex, preoperative myocardial infarction, operative priority, left ventricular ejection fraction, obesity and triple vessel disease. Postoperative morbidities were arrhythmia, wound infection, cerebral infarction, prolonged postoperative hospitalization, pneumonia, acute renal failure, prolonged use of ventilator and operative death. Result: The mean age of total patients was 56.7 years, from 27 to 74. The overall mortality was 6.6%(9 of 137) with the mortality of 3.9%(5 of 128) for elective operation, and 44.4%(4 of 9) for emergent or urgent cases. The morbidity of patients over 65 years was stastistically higher than that of under 65 years. Sex distribution showed no difference in morbidity, however operative mortality rate was slightly higher in women (5/41, 12.19%) than in men(4/96, 4.17%). Morbidity of emergent or urgent operation was 100%, much higher than that of the elective operation. Mortality of the patients whose left ventricular ejection fraction was under 50% was higher than that of those over 50%. Conclusion: We concluded that the risk factors of morbidity after CABG were old age above 65 years and emergent or urgent operation, and that risk factors of mortality were low left venticular ejection fraction under 50% and emergent or urgent operation.

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The Risk of Cervical Spine Injuries among Submersion Patients in River (강에서 발생한 익수 환자의 경추손상 위험도)

  • Kim, Suk Hwan;Choi, Kyung Ho;Choi, Se Min;Oh, Young Min;Seo, Jin Sook;Lee, Mi Jin;Park, Kyu Nam;Lee, Won Jae
    • Journal of Trauma and Injury
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    • v.19 no.1
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    • pp.47-53
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    • 2006
  • Purpose: Recently, the American Heart Association recommended that routine cervical spine protection in submerged patients was not necessary, except in high-energy injury situations. However, until now, this recommendation has few supportive studies and literatures. This retrospective study was performed to demonstrate the risk of cervical spine injury in patients who had been submerged in a river. Methods: Seventy-nine submerged patients who visited St. Mary's Hospital between January 2000 and December 2005 were included in this retrospective study. We investigated and analyzed the victim's age, sex, activity on submersion, mental status and level of severity at admission, prognosis at discharge, associated injuries, and risk group by using the medical records and cervical spine lateral images. According to the activity on submersion, victims were classified into three groups: high risk, low risk, and unknown risk. The reports of radiologic studies were classified into unstable fracture, stable fracture, sprain, degenerative change, and normal. Results: The patients' mean age was 36.8 yrs, and 54% were males. Of the 79 patients, adult and adolescent populations (80%) were dominant. Jumping from a high bridge (48%) was the most common activity on submersion and accounted for 52% of the high-risk group. The Glasgow coma scale at admission and the cerebral performance scale at discharge showed bimodal patterns. The results of the radiologic studies showed one stable fracture, one suspicious stable fracture, and 18 sprains. The incidence of cervical spine fracture in submerged patients was 2.5% in our study. The incidence of cervical spine injury was higher in the high-risk group than it was in the low-risk group, especially in the jumping-from-high-bridge subgroup; however this observation was not statistically significant. No other factors had any significant effect on the incidence of cervical spine injury. Conclusion: Our study showed that even submerged patients in the high risk group had a low incidence of cervical spine fracture and that the prognosis of a patient did not seem to be influenced by the cervical spine fracture itself.

The Analysis of Perchlorate in Nakdong River and Tap Water (낙동강 수계 및 수돗물에서의 Perchlorate($ClO_4^-$) 분석)

  • Kim, Hwa-Bin;Oh, Jeong-Eun;Lee, Sung-Yun;Cho, Jae-Weon;Snyder, Shane
    • Journal of Korean Society of Environmental Engineers
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    • v.28 no.7
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    • pp.776-781
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    • 2006
  • Perchlorate ion($ClO_4^-$), which is present in the solid propellant for rocket, herbicide and some fertilizers. Perchlorate inhibits iodide uptake by the human thyroid gland. Impairment of thyroid function in expectant mothers may impact the fetus and result in effects including cerebral palsy, give rise to thyroid gland cancer. The US EPA(Environmental Protection Agency) adopted a reference dose(RfD) for perchlorate 0.0007 mg/kg-day, and this guidance lead to a Drinking Water Equivalent Level(DWEL) of 24.5 ${\mu}g/L$. The studies about perchlorate are actively performed in foreign countries, especially in USA but there is no study which surveyed the perchlorate contamination in Korea. Therefore, this study was done to investigate perchlorate contamination in Nak-dong river and tap water. The perchlorate was detected in Nakdong river and ranged from ND to 278.4 ${\mu}g/L$. The highest concentration was observed in Kumichon. The perchlorate concentration was decreased with the down stream of Nakdong river. The perchlorate concentration in tap water was varied with the cities and the concentration levels were $ND{\sim}34.1$ ppb. The highest perchlorate concentration was observed in DalsuGoo in Daegu and the similar concentration($9{\sim}11$ ${\mu}g/L$) was detected in most of the districts in Busan. The result of this study suggests that there is a perchlorate source near the Nakdong river and the urgent policy is needed to control perchlorate for the cities which are supplied from Nakdong river as for their tap water.

The Effects of Chungpesagan-Tang Extracts on Reversible Forebrain Ischemia in Sprague-Dawley Rats (청폐사간탕(淸肺瀉肝湯)이 중대뇌동맥 폐쇄 후 재관류에 미치는 영향)

  • Oh, Yean-Hwan;Park, In-Sick;Shin, Gil-Cho;Lee, Won-Chul;Jeong, Sung-Hyun
    • The Journal of Internal Korean Medicine
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    • v.22 no.2
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    • pp.161-174
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    • 2001
  • Objectives : The purpose of this investigation is to evaluate the effect of Chungpesagan-Tang Extracts on reversible forebrain ischemia in Sprague-Dawley rats. Methods : the volume of cerebral infarction and edema, the pathohistological change of neurons, the number of survived neurons, neurotransmitters through immunohistochemical methods, proteins connected with neurotransmitters through immunohistochemical methods and the pathohistological change of neurons through electro-microscopy were investigated. From these reseach data, the protection of neurons and the activity of brain cells were examined. Results : 1. The infaction volume of the control group was 23.9%, and that of the sample group was 16%. 2. The brain edema volume of the control group increased by 17% compared to the normal group and that of the sample group increased by 10%. 3. The light microscopy revealed that the neurons in the ischemia-induced area and CA1 area of hippocampus were most heavily damaged and that the sample group was less damaged compared with the control group. Most pyramidal neurons died in 7 days when brain ischemia was induced. 4. The number of survived pyramidal neurons in the CA1 area of the hippocampus were studied. The normal group had 93 neurons/mm, survived the control group(after 3 days) had 21/mm, the control group(after 7 days) had 3/mm and the sample group 33/mm. 5. The immunohistochemical methods revealed that: (1) In the control group, the sensitivity of GABA, NOS, DBH were increased, and those of Synapsin, eEF-$1{\alpha}$ decreased. NOS and DBH had positive reactions in the control group, but negative in the normal group. (2) In thd sample group, the sensitivity of GABA, NOS, DBH were attenuated, and those of NPY, Synapsin, CaMKII, eEF-$1{\alpha}$ increased when compared to the control group. 6. The electro-microscopy revealed that most neurons died by necrosis and some neurons died by apoptosis. Several imflammation cells appeared in the injured area of neurons. The number of neurons in the sample group that died by ischemia decreased. But, the number that died by apoptosis did not significantly change. Conclusions : The data shows that the effect of Chungpesagan-Tang Extracts on reversible forebrain ischemia in Sprague-Dawley rats is significant.

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Effects of Posttraumatic Hypothermia in an Animal Model of Traumatic Brain Injury(TBI) - Immunohistochemical Stain by TUNEL & β-APP - (실험적 외상성 뇌손상모델에서 외상 후 저체온법의 효과 - TUNEL과 β-APP Immunohistochemical Stain -)

  • An, Byeong Kil;Ha, Young Soo;Hyun, Dong Keun;Park, Chong Oon;Kim, Joon Mee
    • Journal of Korean Neurosurgical Society
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    • v.29 no.4
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    • pp.461-470
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    • 2000
  • Objective : Many investigators have demonstrated the protective effects of hypothermia following traumatic brain injury(TBI) in both animals and humans. It has long been recognized that mild to moderate hypothermia improves neurologic outcomes as well as reduces histologic and biochemical sequelae after TBI. In this study, two immunohistochemical staining using terminal deoxynucleotidyl-transferase-mediated biotin dUTP nick end labeling(TUNEL), staining of apoptosis, and ${\beta}$-amyloid precursor protein(${\beta}$-APP), a marker of axonal injury, were done and the authors evaluated the protective effects of hypothermia on axonal and neuronal injury after TBI in rats. Material and Method : The animals were prepared for the delivery of impact-acceleration brain injury as described by Marmarou and colleagues. TBI is achieved by allowing of a weight drop of 450gm, 1 m height to fall onto a metallic disc fixed on the intact skull of the rats. Fourty Sprague-Dawley rats weighing 400 to 450g were subjected to experimental TBI induced by an impact-acceleration device. Twenty rats were subjected to hypothermia after injury, with their rectal temperatures maintained at $32^{\circ}C$ for 1 hour. After this 1-hour period of hypothermia, rewarming to normothermic levels was accomplished over 30-minute period. Following 12 hours, 24 hours, 1 week and 2 weeks later the animals were killed and semiserial sagittal sections of the brain were reacted for visualization of the apoptosis and ${\beta}$-APP. Results : The density of ${\beta}$-APP marked damaged axons within the corticospinal tract at the pontomedullary junction and apoptotic cells at the contused cerebral cortex were calculated for each animal. In comparison with the untreated controls, a significant reduction in ${\beta}$-APP marked damaged axonal density and apoptotic cells were found in all hypothermic animals(p<0.05). Conclusion : This study shows that the posttraumatic hypothermia result in substantial protection in TBI, at least in terms of the injured axons and neurons.

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