• Neonatal Medicine
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• v.15 no.1
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• pp.32-37
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• 2008

Purpose : Perinatal asphyxia is an important cause of neonatal mortality and subsequent lifelong neurodevelopmental handicaps. Although many treatment strategies have been tested, there is currently no clinically effective treatment to prevent or reduce the harmful effects of hypoxia and ischemia in humans. In the clinical setting, maternal hyperthermia induces adverse effects on the neonatal brain, but recent studies have shown that hyperthermic pretreatment (PT) plays some role in hypoxic-ischemic (HI) injuries of the developing brain. The present study investigated the effect of hyperthermic PT on HI brain injuries in newborn rats. Methods : HI was produced in 7-day-old neonatal rats by unilateral common carotid artery ligation, followed by hypoxia with 8% oxygen at $38^{\circ}C$ for 2 hours. Twenty-four hours before HI, one-half of the pups were exposed to a $40^{\circ}C$ environment for 2 hours. The severity of the brain injury was assessed 7 days after the HI. Results : Hyperthermic PT reduced the gross and histopathologic findings of brain injury from 64.7 to 31.2% (P<0.05). There were no differences in location and severity of injury between the pretreated and control brains. Conclusion : These findings indicate that hyperthermic PT provides neuroprotective benefits on HI in the developing brain. Also, these findings suggest maternal hyperthermia may have protective effect on perinatal HI brain injuries.

• Clinical and Experimental Pediatrics
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• v.52 no.5
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• pp.594-602
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• 2009

Purpose : Transforming growth factor (TGF)-${\beta}1$ reportedly increases neuronal survival by inhibiting the induction of inducible nitric oxide synthase (NOS) in astrocytes and protecting neurons after excitotoxic injury. However, the neuroprotective mechanism of $TGF-{\beta}1$ on hypoxic-ischemic (HI) brain injury in neonatal rats is not clear. The aim of this study was to determine whether $TGF-{\beta}1$ has neuroprotective effects via a NO-mediated mechanism and N-methyl-D-aspartate (NMDA) receptor modulation on perinatal HI brain injury. Methods : Cortical cells were cultured using 19-day-pregnant Sprague-Dawley (SD) rats treated with $TGF-{\beta}1$ (1, 5, or 10 ng/mL) and incubated in a 1% O2 incubator for hypoxia. Seven-day-old SD rat pups were subjected to left carotid occlusion followed by 2 h of hypoxic exposure (7.5% $O_2$). $TGF-{\beta}1$ (0.5 ng/kg) was administered intracerebrally to the rats 30 min before HI brain injury. The expressions of NOS and NMDA receptors were measured. Results : In the in vitro model, the expressions of endothelial NOS (eNOS) and neuronal NOS (nNOS) increased in the hypoxic group and decreased in the 1 ng/mL $TGF-{\beta}1-treated$ group. In the in vivo model, the expression of inducible NOS (iNOS) decreased in the hypoxia group and increased in the $TGF-{\beta}1$-treated group. The expressions of eNOS and nNOS were reversed compared with the expression of iNOS. The expressions of all NMDA receptor subunits decreased in hypoxia group and increased in the $TGF-{\beta}1$-treated group except NR2C. Conclusion : The administration of $TGF-{\beta}1$ could significantly protect against perinatal HI brain injury via some parts of the NO-mediated or excitotoxic mechanism.

• Journal of Chest Surgery
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• v.37 no.2
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• pp.119-130
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• 2004

Decrease in cardiac function after open heart surgery is due to an ischemia induced myocardial damage during surgery, and ischemic preconditioning, a condition in which the myocardial damage does not accumulate after repeated episodes of ischemia but protects itself from damage after prolonged ischemia due to myocytes tolerating the ischemia, is known to diminish myocardial damage, which also helps the recovery of myocardium after reperfusion, and decreases incidences of arrythmia. Our study is performed to display the ischemic preconditioning and show the myocardial protective effect by applying cardioplegic solution to the heart removed from rat. Material and Method: Sprague-Dawley male rats were used, They were fixed on a modified isolated working heart model after cannulation. The reperfusion process was according to non-working and working heart methods and the working method was executed for 20 minutes in which the heart rate, aortic pressure, aortic flow and coronary flow were measured and recorded. The control group is the group which the extracted heart was fixed on the isolated working heart model, recovered by reperfusion 60 minutes after infusion and preserved in the cardioplegic solution 20 minutes after the working heart perfusion and aortic cross clamp, The thesis groups were divided into group I, which ischemic hearts that were hypoxia induced were perfused by cardioplegic solution and preserved for 60 minutes; group II, the cardioplegic solution was infused 45 seconds (II-1), 1 minutes (II-2), 3 minutes (II-3), after the ischemia induction, 20 minutes after working heart perfusion and aortic cross clamp; and group III, hearts were executed on working heart perfusion for 20 minutes and aortic cross clamp was performed for 45 seconds (III-1), 1minute (III-2), 3 minutes (III-3), reperfused for 2 minutes to recover the heart, and then aortic cross clamping was repeated for reperfusion, all the groups were compared based on hemodynamic performance after reperfusion of the heart after preservation for 60 minutes. Result: The recovery time until spontaneous heart beat was longer in groups I, II-3, III-2 and III-3 to control group (p<0.01). Group III-1 (p<0.05) had better results in terms of recovery in number of heart rates compared to control group, and recovered better compared to II-1 (p<0.05). The recovery of aortic blood pressure favored group III-1 (p<0.05) and had better outcomes compared with II-1 (p<0.01). Group III-1 also showed best results in terms of cardiac output (p<0.05) and group III-2 was better compared to II-2 (p<0.05). Group I (p<0.01) and II-3 (p<0.05) showed more cardiac edema than control group. Conclusion: When the effects of other organs are dismissed, protecting the heart by infusion of cardioplegic solution after enforcing ischemia for a short period of time before the onset of abnormal heart beats for preconditioning has a better recovery effect in the cardioplegic group with preconditioning compared to the cardioplegic solution itself. we believe that further study is needed to find a more effective method of preconditioning.

• Biomolecules & Therapeutics
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• v.24 no.3
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• pp.260-267
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• 2016

Mesenchymal stem cells (MSCs) offer significant therapeutic promise for various regenerative therapies. However, MSC-based therapy for injury exhibits low efficacy due to the pathological environment in target tissues and the differences between in vitro and in vivo conditions. To address this issue, we developed adipose-derived MSC spheroids as a novel delivery method to preserve the stem cell microenvironment. MSC spheroids were generated by suspension culture for 3 days, and their sizes increased in a time-dependent manner. After re-attachment of MSC spheroids to the plastic dish, their adhesion capacity and morphology were not altered. MSC spheroids showed enhanced production of hypoxia-induced angiogenic cytokines such as vascular endothelial growth factor (VEGF), stromal cell derived factor (SDF), and hepatocyte growth factor (HGF). In addition, spheroid culture promoted the preservation of extracellular matrix (ECM) components, such as laminin and fibronectin, in a culture time- and spheroid size-dependent manner. Furthermore, phosphorylation of AKT, a cell survival signal, was significantly higher and the expression of pro-apoptotic molecules, poly (ADP ribose) polymerase-1 (PARP-1) and cleaved caspase-3, was markedly lower in the spheroids than in MSCs in monolayers. In the murine hindlimb ischemia model, transplanted MSC spheroids showed better proliferation than MSCs in monolayer. These findings suggest that MSC spheroids promote MSC bioactivities via secretion of angiogenic cytokines, preservation of ECM components, and regulation of apoptotic signals. Therefore, MSC spheroid-based cell therapy may serve as a simple and effective strategy for regenerative medicine.

• The Journal of Korean Medicine
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• v.39 no.3
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• pp.73-80
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• 2018

Carbon monoxide poisoning leads to hypoxia, which eventually leads to tissue ischemia. The delayed neuropsychiatric syndrome can arise in the period from 4 days to 5 weeks following carbon monoxide poisoning. This case report describes a male who suffered from delayed sequelae after self-inflicted carbon monoxide poisoning. At the time of admission, he had symptoms of quadriplegia, both upper limb ankylosis, gait disturbance, and dysuria. He was treated with acupuncture, electro-acupuncture, physical therapy, and Uwhangchungsim-won. Paraplegia improved considerably after 7 days in hospital, and paralysis of the both upper extremities improved after 14 days in hospital. He was able to walk holding on to his wheelchair after 28 days in hospital. He was hospitalized for 55 days and was discharged from the hospital in a fine condition for everyday life. This case report suggests the possibility that korean medicine for delayed neuropsychiatric syndrome.

• Clinical and Experimental Pediatrics
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• v.59 no.11
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• pp.440-445
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• 2016

Purpose: This study aimed to identify prognostic factors of neurological outcomes, including developmental delay, cerebral palsy and epilepsy in late-preterm and term infants with perinatal asphyxia. Methods: All late-preterm and term infants with perinatal asphyxia or hypoxic-ischemic insults who admitted the neonatal intensive care unit of Inje University Sanggye Paik Hospital between 2006 and 2014 and were followed up for at least 2 years were included in this retrospective study. Abnormal neurological outcomes were defined as cerebral palsy, developmental delay and epilepsy. Results: Of the 114 infants with perinatal asphyxia, 31 were lost to follow-up. Of the remaining 83 infants, 10 died, 56 had normal outcomes, and 17 had abnormal outcomes: 14 epilepsy (82.4%), 13 cerebral palsy (76.5%), 16 developmental delay (94.1%). Abnormal outcomes were significantly more frequent in infants with later onset seizure, clinical seizure, poor electroencephalography (EEG) background activity, lower Apgar score at 1 and 5 minutes and abnormal brain imaging (P<0.05). Infants with and without epilepsy showed significant differences in EEG background activity, clinical and electrographic seizures on EEG, Apgar score at 5 minutes and brain imaging findings. Conclusion: We should apply with long-term video EEG or amplitude integrated EEG in order to detect and management subtle clinical or electrographic seizures in neonates with perinatal asphyxia. Also, long-term, prospective studies with large number of patients are needed to evaluate more exact prognostic factors in neonates with perinatal asphyxia.

• The Journal of Korean Physical Therapy
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• v.15 no.4
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• pp.199-207
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• 2003

This review describes the neurophathological mechanisms that are implicated in perinatal brain injury. Perinatal brain injury is the most important cause of morbidity and mortality to infants, often leading to spastic motor deficits, mental retardation, seizures, and learning impairments. The immature brain injury is usually caused by cerebral hypoxia-ischemia, hemorrhage, or infection. The important form of perinatal brain injury is the hypoxic-ischemic injury and the cerebral hemorrhage. The pathology of hypoxic-ischemic injury include delayed energy failure by mitochondrial dysfunction, neuronal excitotoxicity and vulnerability of white matter in developing brain. The immature brain has the fragile vascular bed of germinal matrix and can not effectively centralize their circulation. Therefore, the cerebral hemorrhage process is considered to be involved in the periventricular leukomalacia.

• Clinical and Experimental Pediatrics
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• v.55 no.7
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• pp.238-248
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• 2012

Purpose: Hypoxic-ischemic encephalopathy is an important cause of neonatal mortality, as this brain injury disrupts normal mitochondrial respiratory activity. Carnitine plays an essential role in mitochondrial fatty acid transport and modulates excess acyl coenzyme A levels. In this study, we investigated whether treatment of primary cultures of rat cortical neurons with L-carnitine was able to prevent neurotoxicity resulting from oxygen-glucose deprivation (OGD). Methods: Cortical neurons were prepared from Sprague-Dawley rat embryos. L-Carnitine was applied to cultures just prior to OGD and subsequent reoxygenation. The numbers of cells that stained with acridine orange (AO) and propidium iodide (PI) were counted, and lactate dehydrogenase (LDH) activity and reactive oxygen species (ROS) levels were measured. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and the terminal uridine deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay were performed to evaluate the effect of L-carnitine (1 ${\mu}M$, 10 ${\mu}M$, and 100 ${\mu}M$) on OGD-induced neurotoxicity. Results: Treatment of primary cultures of rat cortical neurons with L-carnitine significantly reduced cell necrosis and prevented apoptosis after OGD. L-Carnitine application significantly reduced the number of cells that died, as assessed by the PI/AO ratio, and also reduced ROS release in the OGD groups treated with 10 ${\mu}M$ and 100 ${\mu}M$ of L-carnitine compared with the untreated OGD group (P<0.05). The application of L-carnitine at 100 ${\mu}M$ significantly decreased cytotoxicity, LDH release, and inhibited apoptosis compared to the untreated OGD group (P<0.05). Conclusion: L-Carnitine has neuroprotective benefits against OGD in rat primary cortical neurons in vitro.

• Toxicological Research
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• v.14 no.4
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• pp.483-488
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• 1998

During cerebral ischemia two important factors such as hypoxia and reduction of glucose can act as modulating stressor affecting the release of amine neurotransmitters including 5-hydroxytryptamine (5-HT). This study was performed to investigate the effect of glucose deprivation on the oxygen deprivation-induced changes of [3H]-5-HT release in the rat hippocampal slices. Experimental groups were divided into 4 groups for this study: normoxic/normoglycemic group, oxygen-deprived group, glucose-deprived group, and oxygen/glucose-deprived group. The hippocampus of rat brain was sliced by 400 $\mu\textrm{m}$ thickness with manual chopper. After 30 minutes preincubation in the normal buffer, the slices were incubated for 20 min in buffer containing [3H]-5-HT (0.1 M, 74 $\mu\textrm$Ci) for uptake. To measure the release of [3H]-5-HT into the buffer, the incubation medium was drained of and refilled with fresh buffer every ten minutes through a sequence of 14 tubes. Oxygen deprivation by gassing with 95% $N_2$/5% $CO_2$ and/or glucose deprivation was done in the 6th and 7th tube. The radioactivities in each buffer and the tissue were counted using scintillation counter. The results were expressed as fractional release. When slices were exposed to oxygen-deprived media for 20 min, the diminution followed by the rebound release of [3H]-5-HT was observed during the post-oxygen deprived period. However, glucose deprivation or oxygen/glucose deprivation markedly increased the release of [3H]-5-HT. which was opposite to the pattern observed in oxygen-deprived group. These results suggested that oxygen deprivation itself inhibits [3H]-5-HT release in rat hippocampal slices during oxygen-deprived period, but additional glucose deprivation convert the inhibitory response to increase of [3H]-5-HT release.

• The Journal of Internal Korean Medicine
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• v.40 no.5
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• pp.957-966
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• 2019

Carbon monoxide intoxication leads to hypoxia, which eventually leads to tissue ischemia. Delayed neuropsychiatric syndrome (DNS) can be a consequence and appears in the form of cognitive impairment and movement disorders after a lucid interval. A 58-year-old Korean male was admitted to our hospital with delayed neuropsychiatric sequelae (DNS) after an 11-day lucid interval following recovery from acute carbon monoxide intoxication. We treated him with herbal medication, acupuncture, electroacupuncture, and moxibustion. The effects were assessed by the activity index and Mini Mental State Examination-Korea (MMSE-K) scores, and by changes in gait disturbance. In this case, the clinical symptoms, including gait disturbance, and the activity index and MMSE-K scores, improved after traditional Korean treatment. The findings of this case report suggest that traditional Korean medicine treatment can be effective for treatment of symptoms of delayed neuropsychiatric sequelae due to CO intoxication.