• Clinical and Experimental Pediatrics
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• v.62 no.12
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• pp.444-449
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• 2019

Background: Sixty percent of infants with severe neonatal hypoxic-ischemic encephalopathy die, while most survivors have permanent disabilities. Treatment for neonatal hypoxic-ischemic encephalopathy is limited to therapeutic hypothermia, but it does not offer complete protection. Here, we investigated whether hypoxia-inducible factor (HIF) promotes cell survival and suggested neuroprotective strategies. Purpose: HIF-1α deficient mice have increased brain injury after neonatal hypoxia-ischemia (HI), and the role of HIF-2α in HI is not well characterized. Copper-zinc superoxide dismutase (SOD)1 overexpression is not beneficial in neonatal HI. The expression of HIF-1α and HIF-2α was measured in SOD1 overexpressing mice and compared to wild-type littermates to see if alteration in expression explains this lack of benefit. Methods: On postnatal day 9, C57Bl/6 mice were subjected to HI, and protein expression was measured by western blotting in the ipsilateral cortex of wild-type and SOD1 overexpressing mice to quantify HIF-1α and HIF-2α. Spectrin expression was also measured to characterize the mechanism of cell death. Results: HIF-1α protein expression did not significantly change after HI injury in the SOD1 overexpressing or wild-type mouse cortex. However, HIF-2α protein expression increased 30 minutes after HI injury in the wild-type and SOD1 overexpressing mouse cortex and decreased to baseline value at 24 hours after HI injury. Spectrin 145/150 expression did not significantly change after HI injury in the SOD1 overexpressing or wild-type mouse cortex. However, spectrin 120 expression increased in both wild-type and SOD1 overexpressing mouse at 4 hours after HI, which decreased by 24 hours, indicating a greater role of apoptotic cell death. Conclusion: HIF-1α and HIF-2α may promote cell survival in neonatal HI in a cell-specific and regional fashion. Our findings suggest that early HIF-2α upregulation precedes apoptotic cell death and limits necrotic cell death. However, the influence of SOD was not clarified; it remains an intriguing factor in neonatal HI.

• Journal of Society of Preventive Korean Medicine
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• v.4 no.2
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• pp.170-192
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• 2000

Objectives : This study was carried out to research antioxidant effects of Sagunja-Tang(SA) through in vitro and vivo experiments, and tried to investigate the relation between oxidation of tissues and deficiency of Qi. Methods and results : HPLC analysis of glycyrrhizine - known to be the main compound of Radix Glycyrrhizae - was done to certify the quality of SA. Chemiluminescence was initiated by adding tort-butyl hydroperoxide (t-BHP) to rabbit polymorphonuclear leukocytes (neutrophils), and generated reactive oxygen species (superoxide anion) decreased significantly by SA as dose dependent manner. Cell injury during 60 minutes tissue incubation was initiated by adding t-BHP, a hydrophobic hydroperoxide and $H_2O_2$, an water soluble oxidant to rat renal cortical and liver slices. Percentage cell death and lipid peroxidation were estimated by measuring lactate dehydrogenase (LDH) and malondialdehyde (MDA), a product of lipid peroxidation. t-BHP induced % cell death of renal cortical slices and lipid peroxidation of renal cortical and liver slices were decreased significantly by SA. SA decreased significantly % cell death and lipid peroxidation of renal cortical and liver slices induced by $H_2O_2$, too. Acute renal and liver injury induced by $HgCl_2\;and\;CCl_4$, which initiated from free radical, were applied to mice and metabolic data were obtained. Data showed protective effects of SA on acute renal injury caused by decrease of glomerular filtration. SA protected acute liver injury too. Conclusions Through this study, we found that SA have antioxidant effects and tissue oxidation was similar to deficiency of Qi. And further studies have to be followed to certify the mechanisms.

• Molecules and Cells
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• v.45 no.4
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• pp.216-230
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• 2022

SERTA domain-containing protein 1 (Sertad1) is upregulated in the models of DNA damage and Alzheimer's disease, contributing to neuronal death. However, the role and mechanism of Sertad1 in ischemic/hypoxic neurological injury remain unclear. In the present study, our results showed that the expression of Sertad1 was upregulated in a mouse middle cerebral artery occlusion and reperfusion model and in HT22 cells after oxygen-glucose deprivation/reoxygenation (OGD/R). Sertad1 knockdown significantly ameliorated ischemia-induced brain infarct volume, neurological deficits and neuronal apoptosis. In addition, it significantly ameliorated the OGD/R-induced inhibition of cell viability and apoptotic cell death in HT22 cells. Sertad1 knockdown significantly inhibited the ischemic/hypoxic-induced expression of p-Rb, B-Myb, and Bim in vivo and in vitro. However, Sertad1 overexpression significantly exacerbated the OGD/R-induced inhibition of cell viability and apoptotic cell death and p-Rb, B-Myb, and Bim expression in HT22 cells. In further studies, we demonstrated that Sertad1 directly binds to CDK4 and the CDK4 inhibitor ON123300 restores the effects of Sertad1 overexpression on OGD/R-induced apoptotic cell death and p-Rb, B-Myb, and Bim expression in HT22 cells. These results suggested that Sertad1 contributed to ischemic/hypoxic neurological injury by activating the CDK4/p-Rb pathway.

• Journal of Korean Neurosurgical Society
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• v.29 no.8
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• pp.1008-1018
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• 2000

Objective : Glutamate induced excitotoxicity is one of the leading causes of cell death under pathologic condition. However, there is controversy whether excitotoxicity may also participate in the neuronal death under low intensity insult such as simple hypoxia or hypoglycemia. To investigate the role of NMDA receptor in low intensity insult, we chose anoxia as the method of injury and used organotypically cultured hippocampal slice as the material of experiment. Materials & Methods : The hippocampal slices cultured for 2-3 weeks were exposed to 60 minutes of complete oxygen deprivation(anoxia). Neuronal death was assessed with Sytox stain. Corrected optical density of fluorescence in gray scale, used as cellular death indicator, was obtained from pictures taken at 24 and 48 hours following the insult. The well-known in vivo phenomenon of regional difference in susceptibility of hippocampal sub-fields to ischemic insult was reproduced in HOSC(hippocampal organotypic slice culture) by complete oxygen deprivation injury. Results : $CA_1$ was the most vulnerable to complete oxygen deprivation in hippocampus while $CA_3$ was resistant. Oxygen deprivation for 10 and 20 minutes with glucose(6.5g/l) present was insufficient to induce neuronal death in the cultured hippocampal slice. However, after 30 minutes exposure under anoxic condition, neuronal death was able to be detected in the center of $CA_1$ area. The intensity and area of fluorescence indicating cell death correlated with the duration of oxygen deprivation. NMDA receptor and non-NMDA receptor blocking with MK-801(30 & $60{\mu}M$) and CNQX($100{\mu}M$) did not provide cellular protection to HOSC against damage induced by oxygen deprivation, but increased intracellular calcium buffering capacity with BAPTA-AM($10{\mu}M$) was effective in preventing neuronal death (p=0.01, Student's t-test). Cycloheximide($1{\mu}g/ml$, $10{\mu}g/ml$) provided no protection to HOSC against insult of complete oxygen deprivation for 60 minutes and combined therapy of MK-801(30 & $60{\mu}M$) and cycloheximide(1 & $10{\mu}g/ml$) was also ineffective in preventing neuronal death. Conclusion : The results of this study show that the another mechanism not associated with glutamate receptor(NMDA & non NMDA) may play major role in cell death mechanisms induced by complete oxygen deprivation and increased intracellular calcium during anoxia may participate in the neuronal death mechanism of oxygen deprivation. Further investigation of the calcium entry channel activated during oxygen deprivation is necessary to understand the neuronal death of anoxia.

• BMB Reports
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• v.31 no.2
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• pp.183-188
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• 1998

2-chloroethylethyl sulfide (CEES) is an alkylating agent that readily reacts with a wide variety of biological molecules causing metabolic abnormality. The mechanism of cell death during CEES injury is poorly understood. We have examined the effect of exposure of thymocytes with various concentrations of CEES to determine the pattern of cell death in thymocytes injury induced by CEES. In the present study, we show that two patterns of cell death occurred by either one of two mechanisms: apoptosis and necrosis. Exposure to low level of CEES (100 ${\mu}M$) for 5 h caused an induction of apoptosis on thymocytes, as identified by the following criteria: DNA fragmentation visualized by the characteristic "ladder" pattern was observed upon agarose gel electrophoresis and morphological features were revealed by microscopical observations. In contrast, exposure to high levels of CEES (500 ${\mu}M$) induce necrotic features such as cell lysis. Thus, depending on the concentrations, CEES can result in either apoptotic or necrotic cell damage. Our findings suggest that thymocytes which are not killed directly, but merely injured by low levels of CEES, are able to activate an internally-programmed cell death mechanism, whereas thymocytes receiving severe damages apparently can not.

• Biomedical Science Letters
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• v.9 no.4
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• pp.189-193
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• 2003

This study was undertaken to investigate the effect of baicalein, a major flavone component of Scutellaria balicalensis Georgi, on oxidant-induced cell injury in renal epithelial cells. Opossum kidney cells, an established proximal tubular epithelial cells, were used as a cell model of renal epithelial cells and t-butylhydroperoxide (tBHP) as an oxidant drug model. Cell viability was measured by MTT assay and lipid peroxidation was estimated by measuring the content of malondialdehyde, a product of lipid peroxidation. Exposure of cells to tBHP caused cell death and its effect was dose-dependent over concentration range of 0.1~1.0 mM. When cells were exposed to tBHP in the presence of various concentrations (0.1~10 $\mu$M) of baicalein, tBHP-induced cell death was prevented with a manner dependent of baicalein concentration. tBHP induced A TP depletion, which was significantly prevented by baicalein. Similarly, tBHP-induced DNA damage was prevented by baicalein. tBHP produced a marked increase in lipid peroxidation and its effect was completely inhibited by baicalein. These results indue ate that tBHP induces cell injury through a lipid peroxidation-dependent mechanism in renal epithelial cells, and baicalein prevented oxidant-induced cell injury via antioxidant action inhibiting lipid peroxidation. In addition, these results suggest that baicalein may be a candidate for development of drugs which are effective in preventing and treating renal diseases.

• Journal of Preventive Medicine and Public Health
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• v.45 no.1
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• pp.8-13
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• 2012

Objectives: Recently injury has become a major world-wide health problem. But studies in Korea about injuries were very few. Thus, this study was conducted to analyze the trend of major injuries from 1991 to 2006 and to provide basic data for preventing injuries. Methods: This study was based on the National Statistical Office data from 1991 to 2006 and calculated to estimate the burden of major injuries by using the standard expected years of life lost (SEYLL) and total lost earnings equation. Results: For transport accidents, mortality, SEYLL and total lost earnings were increased from 1991 to 1996 and decreased from 2000 to 2006. On the other hand, for suicides, these were increased gradually. Since 2003, falls were included in ten leading causes of death. This study showed that injury causes major social and economical losses. Conclusions: We could reduce injury related premature death through active interest in injury prevention program.

• The Korean Journal of Emergency Medical Services
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• v.5 no.1
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• pp.99-107
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• 2001

Injury has now replaced disease as the biggest single cause of death in children after their first birthday. Each month one child dies from preventable, unintentional injury and the medical cost of these injury is increasing remarkably. It is necessary to develop injury prevention system to manage, evaluate and analysis the information about accident. This resource manual developed as a result of literature review of child care safety project which is based on the Kidsafe Tasmanian Division in Australia and the other resources. The purposes of this study is to; 1. Develop model to enable services to focus on injury prevention 2. Develop standardized child care injury report form 3. Develop home safety checklist 4. Development of injury prevention policies The suggestions to develop injury prevention policies : 1. detail analysis of injury occurrence 2. investigation of known intervention and their effectiveness 3. analysis of policy environment 4. development of policy on implementation of intervention 5. develop protocol and materials to develop an injury prevention focus 6. increase knowledge and awareness among staff and parents of where injuries were occurring and develop.

• The Korean Journal of Emergency Medical Services
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• v.27 no.1
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• pp.91-100
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• 2023

Purpose: In patients with major trauma, mortality varies by age. This study aimed to identify predictors of death according to age. Methods: Data from the Community-Based Severe Trauma Survey in Korea were analyzed using a retrospective case-control design. Factors associated with death were identified by age using independent-samples t-tests, Welch's test, and χ² tests. Results: There were statistically significant differences in mortality by sex (p=.006), location (p=.029), mechanism of injury (MOI) (p<.001), intention (p<.001), transportation (p<.001), surgery (p<.001), and Injury Severity Score (ISS) (p<.001) in the ≤44 years age group; by location (p<.001), MOI (p=.004), intention (p<.001), transportation (p<.001), surgery (p<.001), and ISS (p<.001) in the 45-54 years age group; by location (p=.040), MOI (p<.001), transportation (p<.001), transfusion (p<.001), surgery (p<.001), and ISS (p<.001) in the 55-64 years age group; by location (p=.015), intention (p<.001), surgery (p<.001), and ISS (p<.001) in the 65-74 years age group; and by location (p=.002), intention (p<.001), transfusion (p=.020), surgery (p<.001), and ISS (p<.001) in the ≥75 years age group. Conclusion: In patients with major trauma, predictors of mortality varied by age.

• Journal of Korean Medicine Rehabilitation
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• v.23 no.1
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• pp.1-13
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• 2013

Objectives : The pathophysiology of acute spinal cord injury(SCI) may be divided into primary and secondary mechanisms of injury. The secondary mechanism involves free radical formation, excitotoxicity, inflammation and apoptotic cell death, and sets in minutes after injury and lasts for weeks or months. During this phase the spinal tissue damages are aggravated. Therefore, secondary mechanisms of injury serve as a target for the development of neuroprotective drug against SCI. The present study investigated the effect of tetramethylpyrazine(TMP), an active ingredient purified from the rhizome of Ligusticum wallichii(川芎, chuanxiong), on neuronal apoptosis in spinal cord compression injury in rats. Methods : SCI was subjected to rats by a static compression method(35 g weight, 5 mins) and TMP was treated 3 times(30 mg/kg, i.p.) during 48 hours after the SCI. Results : TMP ameliorated the tissue damage in peri-lesion of SCI and reduced TUNEL-labeled cells both in gray matter and in white matter significantly. TMP also attenuated Bax-expressed motor neurons in the ventral horn and preserved Bcl-2-expressed motor neurons. Conclusions : These results indicate that TMP plays a protective role in apoptotic cell death of neurons and oligodendrocytes in spinal cord injury. Moreover, it is suggested that TMP and TMP-containing chuanxiong may potentially delay or protect the secondary spinal injury.