• Annals of Clinical Neurophysiology
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• v.19 no.2
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• pp.136-140
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• 2017

A 77-year-old male with amyotrophic lateral sclerosis had a hypoxic event. After resuscitation, generalized myoclonus appeared and resolved after two days. Five days after the hypoxic event, myoclonic seizures re-emerged right after performing a somatosensory evoked potential and persisted for ten days. Electroencephalogram revealed frequent bi-hemispheric synchronous spike and waves in the central areas. We suggest that somatosensory evoked potential testing may trigger myoclonic status epilepticus. Underlying cortical degeneration associated with amyotrophic lateral sclerosis could attribute to this phenomenon.

• Archives of Pharmacal Research
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• v.20 no.2
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• pp.103-109
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• 1997

The effects of ginseng total saponins (GTS) on hypoxic damage of primary cultures of astrocytes were studied. Hypoxia was created by placing cultures in an air tight chamber that was flushed with 95% $N_2/5%CO_2$ for 15 min before being sealed. Cultures showed evidence of significant cell injury after 24 h of hypoxia (increased lactate dehydrogenase (LDH) content in the culture medium, cell swelling and decreased glutamate uptake and protein content). Addition of GTS (0.1, 0.3 mg/ml) to the cultures during the exposure to hypoxic conditions produced dose-dependent inhibition of the LDH efflux. GTS (0.1, 0.3 mg/ml) also produced significant inhibition of the increased cell volume of astrocytes measured by $[^3H]$ O-methyl-D-glucose uptake under the hypoxic conditions. Decreased glutamate uptake and protein content was inhibited by GTS. These data suggest that GTS prevents astrocytic cell injury induced by severe hypoxia in vitro.

• Molecules and Cells
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• v.38 no.7
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• pp.643-650
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• 2015

The use of conditioned medium from mesenchymal stem cells may be a feasible approach for regeneration of bone defects through secretion of various components of mesenchymal stem cells such as cytokines, chemokines, and growth factors. Mesenchymal stem cells secrete and accumulate multiple factors in conditioned medium under specific physiological conditions. In this study, we investigated whether the conditioned medium collected under hypoxic condition could effectively influence bone regeneration through enhanced migration and adhesion of endogenous mesenchymal stem cells. Cell migration and adhesion abilities were increased through overexpression of intercellular adhesion molecule-1 in hypoxic conditioned medium treated group. Intercellular adhesion molecule-1 was upregulated by microRNA-221 in mesenchymal stem cells because microRNAs are key regulators of various biological functions via gene expression. To investigate the effects in vivo, evaluation of bone regeneration by computed tomography and histological assays revealed that osteogenesis was enhanced in the hypoxic conditioned medium group relative to the other groups. These results suggest that behavioral changes of endogenous mesenchymal stem cells through microRNA-221 targeted-intercellular adhesion molecule-1 expression under hypoxic conditions may be a potential treatment for patients with bone defects.

• Clinical and Experimental Pediatrics
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• v.49 no.2
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• pp.198-202
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• 2006

Purpose : Fas is a cell surface receptor that transduces apoptotic death signals. Interaction of extracelluar domain of Fas with Fas ligand(FasL) triggers the apoptotic process in many diseases. We investigated the expression of Fas and FasL in the hippocampus of 7-day-old newborn rat brains following hypoxia-ischemia injury. Methods : The 7-days-old newborn rats were exposed to 8 percent oxygen for two hours after the ligation of right common carotid arteries. The newborn rats were killed and their brains were removed at 12, 14 and 48 hours after hypoxic-ischemic injury. The expressions of Fas and FasL of the right hippocampus were observed by western blotting and immunofluorescent staining. Results : Fas and FasL were strongly expressed in the right hippocampus ipsilateral to the ligation of the common carotid artery by western blotting at 12 hours following hypoxic-ischemic injury, and then slowly decreased. The immunofluorescent expressions of Fas and FasL strongly increased in the CA1 area of the right hippocampus at 12 and 24 hours following hypoxic-ischemic injury. The immunofluorescent expression of Fas decreased at 48 hours, but the expression of FasL persisted strongly at 48 hours following hypoxic-ischemic injury. Conclusion : The interaction of Fas with FasL on the cell surface may be involved in neuronal injury following hypoxic-ischemic injury in the developing brain.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8251-8257
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• 2014

Apoptosis is one of main types of neural cell death and is reversible and is a major target of therapeutic interventions. However, detailed apoptotic cascades still need to be recognized. In present study, we determined the promotion of HIF-$1{\alpha}$ and survivin in brain samples of a mouse model of hypoxic-ischemia and in neuroblastoma SH-SY5Y cells post hypoxia treatment. Then gain-of-function and loss-of-function strategies were adopted to manipulate the HIF-$1{\alpha}$ in SH-SY5Y cells, and hypoxia-induced survivin upregulation and cell apoptosis were determined. Results demonstrated that the HIF-$1{\alpha}$ and survivin were significantly promoted in a mouse model of hypoxic-ischemia or in SH-SY5Y cells post hypoxia in vitro. Manually upregulated HIF-$1{\alpha}$ could promote the hypoxia-induced survivin upregulation and improve the hypoxia-induced SH-SY5Y cell apoptosis. On the other hand, the HIF-$1{\alpha}$ knockdown by RNAi reduced the hypoxia-induced survivin upregulation and cell apoptosis. Therefore, the present study confirmed the protective role of HIF-$1{\alpha}$ and survivin in the hypoxia-induced SH-SY5Y cell apoptosis, and the survivin upregulation by hypoxia is HIF-$1{\alpha}$-dependent. Promotion of HIF-$1{\alpha}$ and survivin might be a valuable stragegy for therapeutic intervention for hypoxic-ischemic encephalopathy.

• Radiation Oncology Journal
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• v.34 no.4
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• pp.239-249
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• 2016

Tumor hypoxia, a common feature occurring in nearly all human solid tumors is a major contributing factor for failures of anticancer therapies. Because ionizing radiation depends heavily on the presence of molecular oxygen to produce cytotoxic effect, the negative impact of tumor hypoxia had long been recognized. In this review, we will highlight some of the past attempts to overcome tumor hypoxia including hypoxic radiosensitizers and hypoxia-selective cytotoxin. Although they were (still are) a very clever idea, they lacked clinical efficacy largely because of 'reoxygenation' phenomenon occurring in the conventional low dose hyperfractionation radiotherapy prevented proper activation of these compounds. Recent meta-analysis and imaging studies do however indicate that there may be a significant clinical benefit in lowering the locoregional failures by using these compounds. Latest technological advancement in radiotherapy has allowed to deliver high doses of radiation conformally to the tumor volume. Although this technology has brought superb clinical responses for many types of cancer, recent modeling studies have predicted that tumor hypoxia is even more serious because 'reoxygenation' is low thereby leaving a large portion of hypoxic tumor cells behind. Wouldn't it be then reasonable to combine hypoxic radiosensitizers and/or hypoxia-selective cytotoxin with the latest radiotherapy? We will provide some preclinical and clinical evidence to support this idea hoping to revamp an enthusiasm for hypoxic radiosensitizers or hypoxia-selective cytotoxins as an adjunct therapy for radiotherapy.

• The Journal of Korean Medicine
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• v.25 no.2
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• pp.127-137
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• 2004

Objectives : The purpose of this investigation was to evaluate the effects of Sohaphyang-won (SH) on the alteration in gene expression in a hypoxia model using cultured rat cortical cells. Methods : E18 rat cortical cells were grown in neurobasal medium containing B27 supplement. On 12 DIV, SH was added ($20\mu\textrm{g}/ml$) to the culture media for 24 hrs. On 14 DIV, cells were given a hypoxic insult (2% O2/5% CO2, $37^{\circ}C$, 3 hrs), returned to normoxia and cultured for another 24 hrs. Total RNA was prepared from SH-untreated (control) and -treated cultures and alteration in gene expression was analyzed by microarray using rat 5K-TwinChips. Results : Effects on some of the genes whose functions are implicated in neural viability are as follows: 1) For most of the genes altered in expression, the global M values were between -05 to +0.5, Among these, 1517 genes were increased in their expression by more than global M +0.1, while 1480 genes were decreased by more than global M -0.1. 2) The expression of apoptosis-related genes such as Bad (global M =0.35), tumor protein p53 (T53) (global M =0.28) were increased, while v-akt murine thymoma viral oncogene homolog 1 (Akt1) was decreased. 3) The expression of hemoglobin alpha 1 (probably neuroglobin) was increased by about 3.2-fold (global M =1.7). 4) The expression of antioxidation-related catalase gene was increased (global M =0.26). 5) The expression of PKCzeta (prkcz), an upstream kinase of MAPK, was increased (global M =0.29). 6) The expression of retinoic acid receptor alpha (RAR), which may regulate transcription in hypoxic stress, was increased (global M =10.27). Conclusions : In summary, the microarray data suggest that SH doesn't increase the expression of oxygen capture-, anti-oxidation- and 'response to stress' -related genes but decreases some anti-apoptosis genes which would help protect the hypoxic cells from apoptosis.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.1
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• pp.59-64
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• 2012

Hypoxic pulmonary vasoconstriction (HPV) is physiologically important response for preventing mismatching between ventilation and perfusion in lungs. The HPV of isolated pulmonary arteries (HPV-PA) usually require a partial pretone by thromboxane agonist (U46619). Because the HPV of ventilated/perfused lungs (HPV-lung) can be triggered without pretone conditioning, we suspected that a putative tissue factor might be responsible for the pretone of HPV. Here we investigated whether HPV can be also observed in precision-cut lung slices (PCLS) from rats. The HPV in PCLS also required partial contraction by U46619. In addition, $K^+$ channel blockers (4AP and TEA) required U46619-pretone to induce significant contraction of PA in PCLS. In contrast, the airways in PCLS showed reversible contraction in response to the $K^+$ channel blockers without pretone conditioning. Also, the airways showed no hypoxic constriction but a relaxation under the partial pretone by U46619. The airways in PCLS showed reliable, concentration-dependent contraction by metacholine ($EC_{50}$, ~210 nM). In summary, the HPV in PCLS is more similar to isolated PA than V/P lungs. The metacholineinduced constriction of bronchioles suggested that the PLCS might be also useful for studying airway physiology in situ.

• Asian-Australasian Journal of Animal Sciences
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• v.22 no.3
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• pp.336-342
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• 2009

Avian embryos at high altitude are independent of maternal protection against hypoxia, which is contrary to mammals. It is well known that chronic hypoxic exposure at key points can significantly impact on avian development. Tibetan Chicken, a Chinese indigenous breed, living in Tibetan areas with an altitude of 2.2 to 4.1 thousand meters, has an adaptive mechanism to hypoxia. In the present study, fertilized eggs of Tibetan Chicken were incubated under 13% and 21% oxygen concentration. Two lowland chicken breeds, Shouguang Chicken, an indigenous chicken breed in Shandong Province of China, and Dwarf Recessive White Chicken, an imported breed in Beijing, were used as control groups. The embryo mass and some organs such as brain, heart, liver, stomach and eye weight in the three species were measured at Hamburger-Hamilton stage 39, 41, 43 and 45 under hypoxic and normal conditions. The results showed that in hypoxia Tibetan Chicken significantly differed from the two lowland chicken breeds in embryo mass at Hamburger-Hamilton stage 41, 43 and 45 (p<0.01). In particular, Dwarf Recessive White Chicken and Shouguang Chicken showed retarded growth in hypoxic incubation (p<0.01), whereas Tibetan Chicken showed no significant difference between hypoxic and normal conditions (p>0.05). In addition, heart and the other organs showed different susceptibility to hypoxia at the studied stages. In conclusion, chronic hypoxia induced a change in the embryo development of the three different species and Tibetan Chicken showed adaptation to hypoxia. Of note, the embryo developmental physiology of Tibetan Chicken in response to hypoxia will shed light on the process of physiological acclimation or evolutionary adaptation as well as the study of clinical disease.

• BMB Reports
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• v.53 no.11
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• pp.600-604
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• 2020

Macrophages are re-educated and polarized in response to myocardial infarction (MI). The M2 anti-inflammatory phenotype is a known dominator of late stage MI. Mesenchymal stem cells (MSCs) represent a promising tool for cell therapy, particularly heart related diseases. In general, MSCs induce alteration of the macrophage subtype from M1 to M2, both in vitro and in vivo. We conjectured that hypoxic conditions can promote secretome productivity of MSCs. Hypoxia induces TGF-β1 expression, and TGF-β1 mediates M2 macrophage polarization for anti-inflammation and angiogenesis in infarcted areas. We hypothesized that macrophages undergo advanced M2 polarization after exposure to MSCs in hypoxia. Treatment of MSCs derived hypoxic conditioned medium (hypo-CM) promoted M2 phenotype and neovascularization through the TGF-β1/Smad3 pathway. In addition, hypo-CM derived from MSCs improved restoration of ischemic heart, such as attenuating cell apoptosis and fibrosis, and ameliorating microvessel density. Based on our results, we propose a new therapeutic method for effective MI treatment using regulation of macrophage polarization.