• Clinical and Experimental Pediatrics
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• v.64 no.4
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• pp.180-187
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• 2021

Background: Severe perinatal asphyxia results in multiple organ involvement, neonate hospitalization, and eventual death. Purpose: This study aimed to investigate the predictive factors of death in newborns with hypoxic-ischemic encephalopathy (HIE) receiving selective head cooling. Methods: This cross-sectional descriptive-retrospective study was conducted from 2013 to 2018 in Fatemieh Hospital of Hamadan and included 51 newborns who were admitted to the neonatal intensive care unit with a diagnosis of HIE. Selective head cooling for patients with moderate to severe HIE began within 6 hours of birth and continued for 72 hours. The required data for the predictive factors of death were extracted from the patients' medical files, recorded on a premade form, and analyzed using SPSS ver. 16. Results: Of the 51 neonates with moderate to severe HIE who were treated with selective head cooling, 16 (31%) died. There were significant relationships between death and the need for advanced neonatal resuscitation (P=0.002), need for mechanical ventilation (P=0.016), 1-minute Apgar score (P=0.040), and severely abnormal amplitude-integrated electroencephalography (a-EEG) (P=0.047). Multiple regression of variables or data showed that the need for advanced neonatal resuscitation was an independent predictive factor of death (P=0.0075) and severely abnormal a-EEG was an independent predictive factor of asphyxia severity (P=0.0001). Conclusion: All cases of neonatal death in our study were severe HIE (stage 3). Advanced neonatal resuscitation was an independent predictor of death, while a severely abnormal a-EEG was an independent predictor of asphyxia severity in infants with HIE.

• Nutrition Research and Practice
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• v.16 no.2
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• pp.173-193
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• 2022

BACKGROUND/OBJECTIVES: Alzheimer's disease (AD) is one of the most representative neurodegenerative disease mainly caused by the excessive production of amyloid beta (Aβ). Several studies on the antioxidant activity and protective effects of Populus tomentiglandulosa (PT) against cerebral ischemia-induced neuronal damage have been reported. Based on this background, the present study investigated the protective effects of PT against cognitive impairment in AD. MATERIALS/METHODS: We orally administered PT (50 and 100 mg/kg/day) for 14 days in an Aβ_25-35-induced mouse model and conducted behavioral experiments to test cognitive ability. In addition, we evaluated the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum and measured the production of lipid peroxide, nitric oxide (NO), and reactive oxygen species (ROS) in tissues. RESULTS: PT treatment improved the space perceptive ability in the T-maze test, object cognitive ability in the novel object recognition test, and spatial learning/long-term memory in the Morris water-maze test. Moreover, the levels of AST and ALT were not significantly different among the groups, indicating that PT did not show liver toxicity. Furthermore, administration of PT significantly inhibited the production of lipid peroxide, NO, and ROS in the brain, liver, and kidney, suggesting that PT protected against oxidative stress. CONCLUSIONS: Our study demonstrated that administration of PT improved Aβ_25-35-induced cognitive impairment by regulating oxidative stress. Therefore, we propose that PT could be used as a natural agent for AD improvement.

• 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 Ginseng Research
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• v.46 no.1
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• pp.39-53
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• 2022

Ginsenoside Rb₁ (Rb₁), one of the most important ingredients in Panax ginseng Meyer, has been confirmed to have favorable activities, including reducing antioxidative stress, inhibiting inflammation, regulating cell autophagy and apoptosis, affecting sugar and lipid metabolism, and regulating various cytokines. This study reviewed the recent progress on the pharmacological effects and mechanisms of Rb₁ against cardiovascular and nervous system diseases, diabetes, and their complications, especially those related to neurodegenerative diseases, myocardial ischemia, hypoxia injury, and traumatic brain injury. This review retrieved articles from PubMed and Web of Science that were published from 2015 to 2020. The molecular targets or pathways of the effects of Rb₁ on these diseases are referring to HMGB1, GLUT4, 11β-HSD1, ERK, Akt, Notch, NF-κB, MAPK, PPAR-γ, TGF-β1/Smad pathway, PI3K/mTOR pathway, Nrf2/HO-1 pathway, Nrf2/ARE pathway, and MAPK/NF-κB pathway. The potential effects of Rb₁ and its possible mechanisms against diseases were further predicted via Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and disease ontology semantic and enrichment (DOSE) analyses with the reported targets. This study provides insights into the therapeutic effects of Rb₁ and its mechanisms against diseases, which is expected to help in promoting the drug development of Rb₁ and its clinical applications.

• Korean Journal of Radiology
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• v.2 no.4
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• pp.183-191
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• 2001

Objective: To document the signal characteristics of intracerebral hemorrhage (ICH) at evolving stages on diffusion-weighted images (DWI) by comparison with conventional MR images. Materials and Methods: In our retrospective study, 38 patients with ICH underwent a set of imaging sequences that included DWI, T1-and T2-weighted imaging, and fluid-attenuated inversion recovery (FLAIR). In 33 and 10 patients, respectively, conventional and echo-planar T2^* gradient-echo images were also obtained. According to the time interval between symptom onset and initial MRI, five stages were categorized: hyperacute (n=6); acute (n=7); early subacute (n=7); late subacute (n=10); and chronic (n=8). We investigated the signal intensity and apparent diffusion coefficient (ADC) of ICH and compared the signal intensities of hematomas at DWI and on conventional MR images. Results: DWI showed that hematomas were hyperintense at the hyperacute and late subacute stages, and hypointense at the acute, early subacute and chronic stages. Invariably, focal hypointensity was observed within a hyperacute hematoma. At the hyperacute, acute and early subacute stages, hyperintense rims that corresponded with edema surrounding the hematoma were present. The mean ADC ratio was 0.73 at the hyperacute stage, 0.72 at the acute stage, 0.70 at the early subacute stage, 0.72 at the late subacute stage, and 2.56 at the chronic stage. Conclusion: DWI showed that the signal intensity of an ICH may be related to both its ADC value and the magnetic susceptibility effect. In patients with acute stroke, an understanding of the characteristic features of ICH seen at DWI can be helpful in both the characterization of intracranial hemorrhagic lesions and the differentiation of hemorrhage from ischemia.

• Investigative Magnetic Resonance Imaging
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• v.6 no.1
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• pp.55-63
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• 2002

Purpose : We investigated the predictive values of relative CBV measured with perfusion MR imaging, and relative CBF measured with SPECT for tissue outcome in acute ischemic stroke. Material and Methods : Thirteen patients, who had acute unilateral middle cerebral artery occlusion, underwent perfusion MR imaging, and $^{99m}Tc-HMPAO$ SPECT within 6 hours after the onset of symptoms. Lesion-to-contralateral ratios of perfusion parameters were measured, and best cut-off values of both parameter ratios with their accuracy to discriminate between regions with and without evolving infarction were calculated. Results : Mean relative CBV ratios in regions with evolving infarction and without evolving infarction were $0.58{\pm}0.27$ and $0.9{\pm}0.17$ (p < 0.001), and mean relative CBF ratios in those regions were $0.41{\pm}0.22$ and $0.71{\pm}0.14$ (p < 0.001). The best cutoff values to discriminate between regions with and without evolving infarction were estimated to be 0.80 for relative CBV ratio and 0.56 for relative CBF ratio. The sensitivity, specificity and efficiency of each cutoff value were 80.6, 87.5, 82.7% for relative CBV ratio, and 72.2, 75.0, 73.0% for relative CBF ratio (p > 0.05 between two parameters). Conclusion Measurement of relative CBV and relative CBE may be useful in predicting tissue outcome in acute ischemic stroke.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.6
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• pp.1643-1651
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• 2004

This experimental study was designed to investigate the effects of SIEGESBECKIAE HERBA extract (SHE) on the change of cerebral hemodynamics 〔regional cerebral blood flow (rCBF) and mean arterial blood pressure(MABP)〕 in normal condition and cerebral ischemic rats, and to determine the mechanism of action of SHE. This study was designed to investigate whether or not SHE inhibit lactate dehydrogenase (LDH) activity in neuronal cells and cytokines production in serum of cerebral ischemic rats. The results were as follows SHE increased rCBF significantly in a dose-dependent manner, but MABP was not changed by SHE in normal rats. The SHE-induced increase in rCBF was significantly inhibited by pretreatment with indomethacin (IDN), an inhibitor of cyclooxygenase but was increased by methylene blue (MTB), an inhibitor of guanylate cyclase. SHE inhibited lactate dehydrogenase (LDH) activity significantly in neuronal cells. rCBF was increased significantly and stably by SHE(10㎎/㎏, i.p.) during the period of cerebral reperfusion, which contrasted with the findings of rapid and marked increase in control group in ischemic rats. In serum by drawing from femoral arterial blood after middle cerebral arterial occlusion(MCAO) for 1hr and reperfusion for 1hr, the sample group was decreased IL-1β production significantly compared to that of the control group. In serum by drawing from femoral arterial blood after MCAO 1hr and reperfusion 1hr, sample group decreased TNF-α production significantly compared to that of the control grolilp. In serum by drawing from femoral arterial blood after reperfusion 1hr, sample group increased TGF-β production significantly compared to that of the control group. In serum by drawing from femoral arterial blood after MCAO for 1hr and reperfusion for 1hr, IL-10 production of the sample group was similar to that of control group. These results suggested that SHE had inhibitive effect on the brain damage by inhibited LDH activity, IL-1β and TNF-α production, but accelerated TGF-β production.

• Biomolecules & Therapeutics
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• v.15 no.1
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• pp.16-26
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• 2007

Tissue plasminogen activator (tPA) is a serine protease catalyzing the proteolytic conversion of plasminogen into plasmin, which is involved in thrombolysis. During last two decades, the role of tPA in brain physiology and pathology has been extensively investigated. tPA is expressed in brain regions such as cortex, hippocampus, amygdala and cerebellum, and major neural cell types such as neuron, astrocyte, microglia and endothelial cells express tPA in basal status. After strong neural stimulation such as seizure, tPA behaves as an immediate early gene increasing the expression level within an hour. Neural activity and/or postsynaptic stimulation increased the release of tPA from axonal terminal and presumably from dendritic compartment. Neuronal tPA regulates plastic changes in neuronal function and structure mediating key neurologic processes such as visual cortex plasticity, seizure spreading, cerebellar motor learning, long term potentiation and addictive or withdrawal behavior after morphine discontinuance. In addition to these physiological roles, tPA mediates excitotoxicity leading to the neurodegeneration in several pathological conditions including ischemic stroke. Increasing amount of evidence also suggest the role of tPA in neurodegenerative diseases such as Alzheimer's disease and multiple sclerosis even though beneficial effects was also reported in case of Alzheimer's disease based on the observation of tPA-induced degradation of $A{\beta}$ aggregates. Target proteins of tPA action include extracellular matrix protein laminin, proteoglycans and NMDA receptor. In addition, several receptors (or binding partners) for tPA has been reported such as low-density lipoprotein receptor-related protein (LRP) and annexin II, even though intracellular signaling mechanism underlying tPA action is not clear yet. Interestingly, the action of tPA comprises both proteolytic and non-proteolytic mechanism. In case of microglial activation, tPA showed non-proteolytic cytokine-like function. The search for exact target proteins and receptor molecules for tPA along with the identification of the mechanism regulating tPA expression and release in the nervous system will enable us to better understand several key neurological processes like teaming and memory as well as to obtain therapeutic tools against neurodegenerative diseases.

• Journal of Society of Preventive Korean Medicine
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• v.14 no.1
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• pp.111-123
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• 2010

Backgrounds : Stroke is characterized by loss of brain functions due to a disturbance in the blood vessels supplying blood to the brain, and classified into hemorrhage and ischemia. Stroke is known to be affected by genetic factors and other diseases such as hypertension and cardiovascular diseases. However, the distinctive association between stroke and genetic variations has not discovered yet. Objectives : This study investigated the effects of fibrinogen level and genetic variations in FGA (Fibrinogen alpha chain) gene on stroke in Korean stroke patients and controls. Methods : DNA samples from 674 stroke patients diagnosed by Oriental medical hospitals and 267 controls were used in this study. Two common single nucleotide polymorphism(SNP) with high minor allele frequency(MAF), rs2070011G/A of promoter region and nonsynonymous rs6050A/G of exon 5 in FGA gene, were targeted for Taqman genotyping. Because the TOAST classification is important to the factors and symptoms of stroke, ischemic patients were further classified into five subtypes using diagnosis and clinical data. One-way ANOVA and chi-square test were used for clinical data and genetic association, respectively. Haploview v4.1 program was used for linkage disequilibrium(LD), haplotype and haplotype block analysis. Results : The levels of red blood cells and fibrinogen from clinical data were shown to be significant factors for the sub-groups of TOAST classification. No significant associations of stroke, hemorrhage, ischemic and subtypes of TOAST with rs2070011 and rs6050 of FGA gene were found(P > 0.05). However, rs2070011 in promoter region and nonsynonymous rs6050 in exon 5 which produce the amino acid change from threonine to alanine showed a haplotype block and three haplotypes of A-G, G-A, A-A, suggesting that rs2070011 and rs6050 might be co-segregated in generic recombination. Although A-A haplotype of stroke patients showed 64-69% low frequency compared to controls, there was no significant association between stroke and haplotype(P > 0.05). Conclusion : This study showed that there was no significant association between stroke and two SNP of rs2070011G/A and nonsynonymous rs6050A/G in FGA gene. However, these two SNP compose a haplotype block and three haplotypes of A-G, G-A, A-A. This finding suggests that rs2070011 and rs6050 are so close as to be positioned as linkage disequilibrium. Nevertheless, no significant association between haplotypes and stroke was found.

• Journal of agriculture & life science
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• v.46 no.6
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• pp.137-146
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• 2012

This study investigated whether ferulic acid modulates the heme oxygenase (HO)-1 and HO-2 expression in middle cerebral artery occlusion (MCAO)-induced brain injury. Rats (Sprague-Dawley, male) were treated with vehicle or ferulic acid (100 mg/kg, i.v.) before MCAO, and cerebral cortex tissues were collected 24 h after MCAO. This study clearly confirmed the protective effects of ferulic acid during MCAO-induced damage using hematoxylin and eosin staining. MCAO induces nuclear chromatin condensations and necrotic changes with scalloped shrunken form. However, ferulic acid prevented MCAO-induced histopathological changes. HO-1 and HO-2 expression levels were measured using reverse-transcription PCR and Western blot analyses. HO-1 levels were decreased in vehicle-treated animals after MCAO, whereas this decrease in HO-1 levels was attenuated by ferulic acid treatment. However, the level of HO-2 was consistently maintained in the cerebral cortex of vehicle- and ferulic acid-treated animals after MCAO. These results demonstrated that ferulic acid regulates HO-1 expression in ischemic brain injury, while ferulic acid do not modulate HO-2 expression in MACO. In conclusion, these findings suggest that ferulic acid exerts a neuroprotective effect by preventing the MCAO-induced decrease of HO-1 expression.