• The Korean Journal of Nuclear Medicine
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• v.30 no.4
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• pp.484-492
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• 1996

To detect ischemic tissue in experimental model of cerebral ischemia made by middle cerebral artery(MCA)-occlusion, we acquired triple image of $^{99m}Tc$-glucarate, [$^{18}F$]fluoro-deoxyglucose (FDG), and 2,3,5- triphenyltetrazolium (TTC) staining. We made cerebral infarction either with reperfusion (after occlusion of 2 hours) or without reperfusion in 10 Sprague-Dawley rats by inserting thread to MCA through internal carotid artery. After 22 hours, we injected 740 MBq of $^{99m}Tc$-glucarate and 55.5 MBq of [$^{18}F$]FDG through tail vein. Each 1 mm slice of rat brains was frozen and exposed to imaging plate for 20 minutes in freezer to get an [$^{18}F$]FDG image. After 20 hours enough to fade radioactivity of [$^{18}F$]FDG, the slices were again imaged by BAS1500 for $^{99m}Tc$-glucarate uptake. Finally, these brain tissues were stained with TTC. Semi-quantitative visual analysis was done by grading 0 to 3 points according to the degree of uptakes($^{99m}Tc$-glucarate) and decreased uptakes([$^{18}F$]FDG and TTC). Ten rats survived with neurologic symptoms. TTC staining confirmed the development of infarction. The size of the infarction was relatively larger in the group without reperfusion. [$^{18}F$]FDG images were similar to TTC-stained images. However, we found regions with intermediate uptake which were not stained with TTC. We found regions with intermediate [$^{18}F$]FDG uptake where TTC staining was normal. $^{99m}Tc$-glucarate uptake was round only in TTC non-stained region. In the TTC stained regions, there were no uptake of $^{99m}Tc$-glucarate. We could not find clear relation between $^{99m}Tc$-glucarate uptake with [$^{18}F$]FDG uptake. This was partly because percent uptake of $^{99m}Tc$-glucarate was so small (less than 1 percent of injected dose) and because there were quite heterogeneity of patterns of [$^{18}F$]FDG uptake and TTC. With these findings, we could conclude that $^{99m}Tc$-glucarate were taken up only in part of ischemic tissues which were proven to be nonviable. The establishment of MCA-occluded rat model with or without reperfusion and triple imaging for $^{99m}Tc,\;^{18}F$ and TTC helped the characterization of $^{99m}Tc$-glucarate uptakes. Further work is needed to clarify the meaning or diversities or [$^{18}F$]FDG and TTC and their relation with $^{99m}Tc$-glucarate.

• Journal of Acupuncture Research
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• v.24 no.1
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• pp.111-125
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• 2007

Objection : The aim of this study was to investigate anti-ischemic effect of LR1 ${\cdot}$ HT8 ${\cdot}$ HT9 Reinforcement in Acupuncture. Methods : I designed to investigate whether LR1 ${\cdot}$ HT8 ${\cdot}$ HT9 Reinforcement in Acupuncture affects cerebral hemodynamics [regional cerebral blood flow(rCBF), pial arterial diameter(PAD), mean arterial blood pressure (MABP) ] in normal and cerebral ischemia rats by MCA occlusion method, and to make manifest whether LR1 ${\cdot}$ HT8 ${\cdot}$ HT9 Reinforcement in Acupuncture is mediated by cyclooxygenase or guanylate cyclase. The changes of rCBF and MABP were determinated by laser-doppler flowmetry(LDF), and the change of PAD was determinated by video microscope and width analyzer. Results: The results were as follows ; 1. LR1 ${\cdot}$ HT8 ${\cdot}$ HT9 Reinforcement in Acupuncture was significantly increased rCBF, PAD, but decreased MABP after withdrawing of the needle. This results suggest that LR1 ${\cdot}$ HT8 ${\cdot}$ HT9 Reinforcement in Acupuncture induced significantly rCBF by dilating PAD. 2. Pretreatment with indomethacin (1mg/kg, i.v.) was significantly inhibited LR1 ${\cdot}$ HT8 ${\cdot}$ HT9 Reinforcement in Acupuncture induced increase of rCBF and PAD, but increased LR1 ${\cdot}$ HT8 ${\cdot}$ HT9 Reinforcement in Acupuncture induced decrease of MABP after withdrawing of the needle. 3. Pretreatment with methylene blue(10/${\mu}$g/kg, i.v.) was decreased LR1 ${\cdot}$ HT8 ${\cdot}$ HT9 Reinforcement in Acupuncture induced increase of rCBF and MABP, but accelerated LR1 ${\cdot}$ HT8 ${\cdot}$ HT9 Reinforcement in Acupuncture induced decrease of PAD. This results suggest that the mechanism of LR1 ${\cdot}$ HT8 ${\cdot}$ HT9 Reinforcement in Acupuncture is mediated by cyclooxygenase or guanylate cyclase. Conclusion : I suggest that LR1 ${\cdot}$ HT8 ${\cdot}$ HT9 Reinforcement in Acupuncture has an anti-ischemic effect through the improvement of cerebral hemodynamics, and the mechanism IS mediated by cyclooxygenase.

• Herbal Formula Science
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• v.13 no.1
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• pp.49-69
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• 2005

This Study was designed to investigate the effect of Sunkihwalhyul -Tang extract(SHT) on the change of cerebral hemodynamics [regional cerebral blood flow(rCBF), pial arterial diameter(PAD) and mean arterial blood pressure(MABP)] in normal and cerebral ischemic rats, and further to determine the mechanisms of action of SHT on hemodynamics. In addition, this study was designed to investigate whether SHT inhibits lactate dehydrog enase(LDH) activity in neuronal cells and cytokines production in serum of cerebral ischemic rats. The results were as follows 1. SHT significantly increased rCBF and PAD in a dose-dependent manner, but MABP was not changed by injecting SHT. These results suggest that SHT significantly increases rCBF by dilating PAD. 2. The SHT-induced increase in rCBF was significantly inhibited by pretreatment with indomethacin(IDN, 1 mg/kg, i.p.), an inhibitor of cyclooxygenase and methylene blue(MTB, $10{\mu}g/kg$, i.p.), an inhibitor of guanylate cyclase. 3. The SHT-induced dilation in PAD was significantly inhibited by pretreatment with IDN and MTB. 4. The SHT-induced some increase in MABP was significantly increased by pretreatment with IDN. These results suggest that the mechanism of action of SBT is mediated by guanylate cyclase. 5. Both rCBF and PAD were significantly and stably increased by SHT(10 mg/kg, i.p.) during the period of cerebral reperfusion, which contrasted with the findings of rapid and marked increase in control group. 6. SBH significantly inhibited LDH activity in neuronal cells. These results suggest that SHT prevents the neuronal death. 7. In cytokine production in the senlm drawn from femoral artery 1 hr after middlecerebral arterial occlusion, sample group showed significantly decreased production of IL-1$\beta$ production, decreased production TNF-$\alpha$ and increased Production of IL-10 compared with control group. 8. In cytokine production in the serum drawn femoral artery 1 hr after reperfusion, sample group showed significantly decreased production of IL-1$\beta$ and TNF-$\alpha$ as wellas significantly increased production of IL10 compared with control group. These results suggest that SHT mediated by guanylate cyclase has inhibitive effect on the brain damage by inhibiting LDH activity, IL-1$\beta$ and TNF-$\alpha$ production, and by accelerating IL-10 production. The present author thinks that SHT has an anti-ischemic effects through the improvement of cerebral hemodynamics and inhibitive enects on the brain damage.

• Journal of Sasang Constitutional Medicine
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• v.15 no.1
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• pp.72-89
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• 2003

To elucidate the neuroprotective effect of Yeoldahanso-tang(YHT) on nerve cells damaged by hypoxia, the cytotoxic effects of exposure to hypoxia were determined by XTT(SODIUM3,3'-{I-[(PHENYLAMINO) CARBONYL]-3,4-TETRAZOLIUM}- BIS (4-METHOXY-6-NITRO) BENZENE SULFONIC ACID HYDRATE), NR(Neutral red), MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and SRB(Sulforhodamin B) asssay. The activity of catalase and SOD(Superoxide dismutase) was measured by spectrophometry, and $TNF-{\alpha}$(Tumor cell necrosis $fector-{\alpha}$) and PKC(Protein kinase C) activity was measured after exposure to hypoxia and treatment of YHTWE. Also the neuroprotective effect of YHTWE was researched for the elucidatioion of neuroprotective mechanism. The results were as follows; 1. Hypoxia decreased cell viability measured by XTT, NR assay when cultured cerebral neurons were exposed to 95% N2/5% CO2 for $2{\sim}26$ minutes in these cultures and YHTWE inhibited the decrease of cell viability. 2. H2O2 treatment decreased cell viability measured by MTT, and SRB assay when cultured cerebral neurons were exposed to 1-80 ${\mu}M$ for 6 hours, but YHTWE inhibited the decrease of cell viability. 3. Hypoxia decreased catalase and SOD activity, and also $TNF-{\alpha}$ and PKC activity in these cultured cerebral neurons, but YHTWE inhibited the decrease of the catalase and SOD activity in these cultures. 4. Hypoxia triggered the apoptosis via caspase activation and internucleosomal DNA fragmentation. Also hypoxia stimulate the release of cytochrome c forom mitochondria. YHTWE inhibited the apoptosis via caspase activation induced by hypoxia. From these results, it can be suggested that brain ischemia model induced hypoxia showed neurotoxicity on cultured mouse cerebral neurons, and the YHTWE has the neuroprotective effect in blocking the neurotoxicity induced by hypoxia in cultured mouse cerebral neurons.

• Journal of Korean Neurosurgical Society
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• v.30 no.7
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• pp.831-841
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• 2001

Objective : Somatosensory evoked potentials(SSEPs) have been used widely both experimentally and clinically to monitor the function of central nervous system and peripheral nervous system. Studies of SSEPs have reported the various recording techniques and patterns of SSEP. The previous SSEP studies used scalp recording electrodes, showed mean vector potentials which included relatively constant brainstem potentials(far-field potentials) and unstable thalamocortical pathway potentials(near-field potentials). Even in invasive SSEP recording methods, thalamocortical potentials were variable according to the kinds, depths, and distance of two electrodes. So they were regarded improper method for monitoring of upper level of brainstem. The present study was conducted to investigate the characteristics of somatosensory evoked field potentials(SSEFPs) of the cerebral cortex that evoked by hindlimb stimulation using ball electrode and the pathways of SSEFP by recording the potentials simultaneously in the cortex, VPL nucleus of thalamus, and nucleus gracilis. Methods : In the first experiment, a specially designed recording electrode was inserted into the cerebral cortex perpendicular to the cortical surface in order to recording the constant cortical field potentials and SSEFPs mapped from different areas of somatosensory cortex were analyzed. In the second experiment, SSEPs were recorded in the ipsilateral nucleus gracilis, the contralateral ventroposterolateral thalamic nucleus(VPL), and the cerebral cortex along the conduction pathway of somatosensory information. Results : In the first experiment, we could constantly obtain the SSEFPs in cerebral cortex following the transcutaneous electrical stimulation of the hind limb, and it revealed that the first large positive and following negative waves were largest at the 2mm posterior and 2mm lateral to the bregma in the contralateral somatosensory cortex. The second experiment showed that the SSEPs were conducted by way of posterior column somatosensory pathway and thalamocortical pathway and that specific patterns of the SSEPs were recorded from the nucleus gracilis, VPL, and cerebral cortex. Conclusion : The specially designed recording electrode was found to be very useful in recording the localized SSEFPs and the transcutaneous electrical stimulation using ball electrode was effective in evoking SSEPs. The characteristic shapes, latencies, and conduction velocities of each potentials are expected to be used the fundamental data for the future study of brain functions, including the hydrocephalus model, middle cerebral artery ischemia model, and so forth.

• The Korean Journal of Physiology and Pharmacology
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• v.8 no.2
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• pp.77-81
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• 2004

The loss of neurons and synaptic contacts following cerebral ischemia may lead to a synaptic plastic modification, which may contribute to the functional recovery after a brain lesion. Using synapsin I and GAP-43 as markers, we investigated the neuronal cell death and the synaptic plastic modification in the rat hippocampus of a middle cerebral artery occlusion (MCAO) model. Cresyl violet staining revealed that neuronal cell damage occurred after 2 h of MCAO, which progressed during reperfusion for 2 weeks. The immunoreactivity of synapsin I and GAP-43 was increased in the stratum lucidum in the CA3 subfield as well as in the inner and outer molecular layers of dentate gyrus in the hippocampus at reperfusion for 2 weeks. The immunoreactivity of phosphosynapsin was increased in the stratum lucidum in the CA3 subfield during reperfusion for 1 week. Our data suggest that the increase in the synapsin I and GAP-43 immunoreactivity probably mediates either the functional adaptation of the neurons through reactive synaptogenesis from the pre-existing presynaptic nerve terminals or the structural remodeling of their axonal connections in the areas with ischemic loss of target cells. Furthermore, phosphosynapsin may play some role in the synaptic plastic adaptations before or during reactive synaptogenesis after the MCAO.

• Clinical and Experimental Pediatrics
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• v.61 no.8
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• pp.245-252
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• 2018

Purpose: This study investigated patterns of ischemic injury observed in brain images from patients with neonatal group B Streptococcal (GBS) meningitis. Methods: Clinical findings and brain images from eight term or near-term newborn infants with GBS meningitis were reviewed. Results: GBS meningitis was confirmed in all 8 infants via cerebrospinal fluid (CSF) analysis, and patients tested positive for GBS in both blood and CSF cultures. Six infants (75.0%) showed early onset manifestation of the disease (<7 days); the remaining 2 (25.0%) showed late onset manifestation. In 6 infants (75%), cranial ultrasonography showed focal or diffuse echogenicity, suggesting hypoxic-ischemic injury in the basal ganglia, cerebral hemispheres, and periventricular or subcortical white matter; these findings are compatible with meningitis. Findings from magnetic resonance imaging (MRI) were compatible with bacterial meningitis, showing prominent leptomeningeal enhancement, a widening echogenic interhemisphere, and ventricular wall thickening in all infants. Restrictive ischemic lesions observed through diffusion-weighted imaging were evident in all eight infants. Patterns of ischemic injury as detected through MRI were subdivided into 3 groups: 3 infants (37.5%) predominantly showed multiple punctuate lesions in the basal ganglia, 2 infants (25.0%) showed focal or diffuse cerebral infarcts, and 3 infants (37.5%) predominantly showed focal subcortical or periventricular white matter lesions. Four infants (50%) showed significant developmental delay or cerebral palsy. Conclusion: Certain patterns of ischemic injury are commonly recognized in brain images from patients with neonatal GBS meningitis, and this ischemic complication may modify disease processes and contribute to poor neurologic outcomes.

• 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 Korea Journal of Herbology
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• v.27 no.2
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• pp.77-83
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• 2012

Objectives : This work was designed to investigate the effect of The root of Achyranthes japonica Nakai (AJN) water extract on serum deprivation reperfusion-induced apoptosis in PC-12 cells and transient middle cerebral artery occlusion (tMCAO)-induced ischemic brains of rats. Methods : Apoptosis in PC12 cells was induced by serum deprivation and reperfusion. The cells were treated with AJN water extract at doses of 0.5 and 1.0 mg/ml for 24 hr after inducing the apoptosis. Cell viability was determined by WST-1 assay. The expression of caspase-3 protein was determined by Western blot. Ischemic brains were prepared from tMCAO-induced ischemic rats after oral administration with AJN at dose of 50 and 100 mg/kg, and then brain infarction was measured by TTC staining. Results : AJN significantly increased the cell viability in apoptocic-induced PC-12 cells, and also decreased the expression of caspase-3 protein. Furthermore, the administration of AJN significantly inhibited tMCAO-induced brain infarction in rats. Conclusions : Our results suggest that AJN extract has a neuroprotective property via suppressing the apoptosis in PC12 cells and the infarction of ischemic brains.

• 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.