• The Journal of Korean Medicine
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• v.31 no.5
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• pp.82-89
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• 2010

Objectives: The aim of this study was to determine distribution patterns of TOAST subtypes of ischemic stroke patients admitted to oriental hospitals and to get a better understanding of present conditions in oriental medicine by comparing with the Korea stroke registry (KSR), the largest and representative data. Methods: Clinical data were collected from acute ischemic stoke patients. MRI studies including vascular images were performed in all cases. TOAST criteria were used to determine subtypes of ischemic stroke patients. According to the duration from disease onset to hospital admission time, patients were assigned to 3 groups (Group I0 to 3 d, Group II4 to 7 d, Group III8 to 28 d) and the distribution of TOAST subtypes were compared among these three groups. Results: We collected 514 sets of clinical data from 10 oriental hospitals between May 2007 and September 2009. Small vessel occlusion (SVO) subtype was the most common (57.62%), followed by large artery atherosclerosis (LAA, 29.98%). Compared with TOAST distribution of KSR, the proportion of ischemic stroke patients with SVO subtype was higher than that of KSR. On the other hand the proportion of patients with stroke of undetermined etiology (SUE) was lower. Distributions of SVO, LAA and cardioembolism (CE) in group were I 66.4%, 23.8% and 8.9%, respectively; those in group IIIwere 51.03%, 34.71% and 11.57%, respectively. Conclusions: In oriental hospitals, the proportion of ischemic stroke patients diagnosed as SVO type was higher than that of KSR. At early stage (from onset to 2 d) proportion of SVO was very high, however after 7 days from onset it decreased with concomitant increases in proportions of LAA and CE. These phenomena may be due to the facts that 1) at early stage emergency treatments are limited in oriental hospitals, 2) after early stage many patients prefer oriental treatments, including rehabilitation.

• Journal of Sasang Constitutional Medicine
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• v.18 no.2
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• pp.125-132
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• 2006

1. Objectives The purpose of this study was to examine the regional cerebral blood-flow(r-CBF) difference between OMT(Oriental Music Therapy) group and control group using brain SPECT, to evaluate the effect of OMT in ischemic stroke patients Classified by Sasang Constitutional. 2. Methods We selected 10 ischemic storke patients, classified groups into OMT group or control group. r-CBF of two groups were examined by brain SPECT. in all group we applied SCM(Sasang constitutional medicine)treatment for 4-5 weaks, and additionally in OMT group We applied OMT for 4-5 weaks. after that all the r-CBF of two groups took brain SPECT again. r-CBF difference and change before and after SCM treatment and OMT were quantified and analyzed using SPM. 3. Results r-CBF of OMT groups were increased compared to control groups. 4. Conclusions This study demonstrated that Sasang Constitutional OMT increased regional cerebral blood perfusion to the corresponding brain areas in ischemic stroke patients.

• Journal of Korean Neurosurgical Society
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• v.50 no.3
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• pp.173-178
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• 2011

Objective : The rat middle cerebral artery thread-occlusion model has been widely used to investigate the pathophysiological mechanisms of stroke and to develop therapeutic treatment. This study was conducted to analyze energy metabolism, apoptotic signal pathways, and genetic changes in the hippocampus of the ischemic rat brain. Methods : Focal transient cerebral ischemia was induced by obstructing the middle cerebral artery for two hours. After 24 hours, the induction of ischemia was confirmed by the measurement of infarct size using 2,3,5-triphenyltetrazolium chloride staining. A cDNA microarray assay was performed after isolating the hippocampus, and was used to examine changes in genetic expression patterns. Results : According to the cDNA microarray analysis, a total of 1,882 and 2,237 genes showed more than a 2-fold increase and more than a 2-fold decrease, respectively. When the genes were classified according to signal pathways, genes related with oxidative phosphorylation were found most frequently. There are several apoptotic genes that are known to be expressed during ischemic brain damage, including Akt2 and Tnfrsf1a. In this study, the expression of these genes was observed to increase by more than 2-fold. As energy metabolism related genes grew, ischemic brain damage was affected, and the expression of important genes related to apoptosis was increased/decreased.Conclusion : Our analysis revealed a significant change in the expression of energy metabolism related genes (Atp6v0d1, Atp5g2, etc.) in the hippocampus of the ischemic rat brain. Based on this data, we feel these genes have the potential to be target genes used for the development of therapeutic agents for ischemic stroke.

• Journal of Acupuncture Research
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• v.27 no.4
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• pp.29-38
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• 2010

Objectives : The purpose of the study is to determine the neuroprotective effect of modified Boyanghwano-tang(mBHT), a traditional Korean medicine, on the transient focal cerebral ischemia in rats. Methods : Focal ischemia and reperfusion were induced by middle cerebral artery occlusion(MCAO) for 90 min, followed by 144 h reperfusion in rats. mBHT(200mg/kg body weight, p.o.) was administrated in rats once a day during reperfusion. At the end of treatment, brain infarction was measured by TTC staining, and histological change was observed by H&E staining. The expressions of Bax, Bcl-2 and cytochrome c in ischemic brains were determined by immunofluorescent analysis. Results : mBHT significantly reduced the cerebral infarct volumes of the MCAO rats. mBHT also attenuated the neuronal cell death and the expressions of pro-apoptotic molecules, bax and cytochrome c in ischemic brains. Further, mBHT significantly increased the survival time of ischemeic rats and the expression of anti-apoptotic molecule, Bcl-2 in ischemic brains. Conclusions : Our results suggest that mBHT is neuroprotective and may prove to be useful adjunct in the treatment of ischemic stroke.

• Clinical and Experimental Pediatrics
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• v.64 no.12
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• pp.608-618
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• 2021

Hypoxic-ischemic encephalopathy (HIE) is the most common cause of neonatal encephalopathy with a global incidence of approximately 1 to 8 per 1,000 live births. Neonatal encephalopathy can cause neurodevelopmental and cognitive impairments in survivors of hypoxic-ischemic insults with and without functional motor deficits. Normal neurodevelopmental outcomes in early childhood do not preclude cognitive and behavioral difficulties in late childhood and adolescence because cognitive functions are not yet fully developed at this early age. Therapeutic hypothermia has been shown to significantly reduced death and severe disabilities in term newborns with HIE. However, children treated with hypothermia therapy remain at risk for cognitive impairments and follow-up is necessary throughout late childhood and adolescence. Novel adjunctive neuroprotective therapies combined with therapeutic hypothermia may enhance the survival and neurodevelopmental outcomes of infants with HIE. The extent and severity of brain injury on magnetic resonance imaging might predict neurodevelopmental outcomes and lead to targeted interven tions in children with a history of neonatal encephalopathy. We provide a summary of the long-term cognitive outcomes in late childhood and adolescence in children with a history of HIE and the association between pattern of brain injury and neurodevelopmental outcomes.

• Clinical and Experimental Pediatrics
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• v.64 no.8
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• pp.422-429
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• 2021

Background: Carnosine has antioxidative and neuroprotective properties against hypoxic-ischemic (HI) brain injury. Hypothermia is used as a therapeutic tool for HI encephalopathy in newborn infants with perinatal asphyxia. However, the combined effects of these therapies are unknown. Purpose: Here we investigated the effects of combined carnosine and hypothermia therapy on HI brain injury in neonatal rats. Methods: Postnatal day 7 (P7) rats were subjected to HI brain injury and randomly assigned to 4 groups: vehicle; carnosine alone; vehicle and hypothermia; and carnosine and hypothermia. Carnosine (250 mg/kg) was intraperitoneally administered at 3 points: immediately following HI injury, 24 hours later, and 48 hours later. Hypothermia was performed by placing the rats in a chamber maintained at 27℃ for 3 hours to induce whole-body cooling. Sham-treated rats were also included as a normal control. The rats were euthanized for experiments at P10, P14, and P35. Histological and morphological analyses, in situ zymography, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assays, and immunofluorescence studies were conducted to investigate the neuroprotective effects of the various interventional treatments. Results: Vehicle-treated P10 rats with HI injury showed an increased infarct volume compared to sham-treated rats during the triphenyltetrazolium chloride staining study. Hematoxylin and eosin staining revealed that vehicle-treated P35 rats with HI injury had decreased brain volume in the affected hemisphere. Compared to the vehicle group, carnosine and hypothermia alone did not result in any protective effects against HI brain injury. However, a combination of carnosine and hypothermia effectively reduced the extent of brain damage. The results of in situ zymography, TUNEL assays, and immunofluorescence studies showed that neuroprotective effects were achieved with combination therapy only. Conclusion: Carnosine and hypothermia may have synergistic neuroprotective effects against brain damage following HI injury.

• Archives of Pharmacal Research
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• v.25 no.5
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• pp.697-703
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• 2002

We investigated that the role of nitric oxide (NO) on ischemic rats in brain and heart. Ischemia was induced by both common carotid arteries (CCA) occlusion for 24h following reperfusion. Then tissue samples were removed and measured NOx. In brain, NOx was increased by about 40% vs. normal and it was significantly inhibited by aminoguanidine, selective iNOS inhibitor. This result showed that NOx concentration was increased by iNOS. We investigated the role of $Ca^{2+}$ during ischemia. Nimodipine, L-type calcium channel blocker, didn't inhibit the increases of NOx concentration during ischemia. It suggested that increased NOx was due to calcium-independent NOS. MK-801, which N-methyl-D-aspartate (NMDA) receptor antagonist, didn't significantly prevent the increases of NOx. In heart, ischemia caused NOx decrease and it is inconsistent with NOx increase in brain. Aminoguanidine and nimodipine didnt affect on NOx decrease. But MK-801 more lowered NOx concentration than those of ischemia control group. It seemed that $Ca^{2+}$ influx in heart partially occurred via NMDA receptor and inhibited by NMDA receptor antagonist. The mean arterial pressure (MAP) in ischemic rats after 24h of CCA occlusion was decreased when compared to normal value, whereas the heart rates (HR) was not different between two groups. Aminoguanidine or MK801 had no effect on MAP or HR, but nimodipine reduced MAP. There was no difference the effects of aminoguanidine, nimodipine, or MK-801, on MAP and HR between normal rats and ischemic rats. In summary, ischemic model caused an increase of NOx concentration, suggesting that this may be produced via iNOS, which is calcium independent in brain. However in heart, ischemia decreased NOx concentration and NMDA receptor was partially involved. The basal MAP was decreased in ischemic rats but HR was not different from normal control, suggesting that increased NOx in brain of ischemic rat may result in the hypotension.

• Journal of Oriental Neuropsychiatry
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• v.17 no.3
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• pp.45-56
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• 2006

Objective: Yukmijibwang-Tang(UJT) has been used for Dementia derived by deficiency of Kidney-Yin in the oriental medicine. This study was planned to examine the effects of UJT on the memory loss induced by focal brain ischemic injury in the rats. Methods : Experimental groups were divided into 4 groups ; Normal group, Control group, UJT1 group and UJT2 group. Control group were no treated after focal brain ischemic injury. UJT1 group were administered UJT 0.3 $m{\ell}/kg$ to focal brain ischemic injuried rats for 21 days, UJT2 group were administered UJT 1.2 $m{\ell}/kg$ to focal brain ischemic injuried rats for 21 days. The present author observed the number of errors on the eight-arm radial maze task, the rate of correct choice on the eight-arm radial maze task, the values of density of Cresy1 violet- stained sections in the hippocampal CA1 and the values of density of Acetlycholine Esterase (AchE)stained nuclei in the hippocampal CA1. Results : The number of errors in the Eigth-arm radial maze task was significantly decreased in UJT1 group on 1, 2, 3, 5, 6days, And it was significantly decreased in UJT2 group on 1-6days compared with control group. The rate of correct choice in the eight-arm radial maze task was significantly increased in UJT1, UJT2 group compared with control group. The values of density of Cresyl violet-stained stained sections in the hippocampal CA1 were significantly increased in UJT1, UJT2 group compared with control group. The values of density of AchE in the hippocampal CA1 were increased in UJT1, UJT2 group compared with control group, but the values were not significant. Conclusions: The present author thought that Yukmijihwang-Tang could he used for curing dementia induced by focal brain ischemic injury.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.4
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• pp.993-999
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• 2005

This research was peformed to investigate protective effect of Sophora Subprostrata fractions against focal ischemic brain damage after middle cerebral artery(MCA) occlusion using intraluminal suture. Rats were divided into six groups: MCA-occluded group(Control): each administered groups with Sophora Subprostrata total phase(Total), Sophora Subprostrata Aqueous phase (Aqueous), Sophora Subprostrata BuOH phase(BuOH), and Sophora Subprostrata Alkaloid phase(Alkaloid) after MCA-occlusion; sham-operated group(Sham). The right MCA was occluded by A poly-L-lysine coated 4-0 nylon suture thread through the internal carotid artery permanently. Sophora Subprostrata and fractions were administered orally(Smg/ml) for 7 days after MCA-occlusion. The Drain tissue was stained with $2\%$ triphenyl tetrazolium chloride on ischemic brain tissue(2mm section). The results showed that 1) Sophora Subprostrata total phase reduced infarct size and total infarct volume compared to the control group at 24 hours after MCA-occlusion, 2) Sophora Subprostrata Aqueous phase reduced infarct size and total infarct volume compared to the control group at 24 hours after MCA-occlusion, 3) Sophora Subprostrata Alkaloid phase reduced infarct size compared to the control group at 24 hours after MCA-occlusion, but 4) at 7 days after MCA-occlusion, Sophora Subprostrata did not show effective recovery compared with control group. Sophora Subprostrata has protective effects against brain damage at the early stage of focal cerebral ischemia. Sophora Subprostrata total and Aqueous phase produced more pronounced protective effect against focal ischemic brain damage.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.5
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• pp.423-431
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• 2020

This study aimed to evaluate the effect of curcumin on brain hypoxic-ischemic (HI) damage in neonatal rats and whether the phosphoinositide 3-kinase (PI3K)/Akt/vascular endothelial growth factor (VEGF) signaling pathway is involved. Brain HI damage models were established in neonatal rats, which received the following treatments: curcumin by intraperitoneal injection before injury, insulin-like growth factor 1 (IGF-1) by subcutaneous injection after injury, and VEGF by intracerebroventricular injection after injury. This was followed by neurological evaluation, hemodynamic measurements, histopathological assessment, TUNEL assay, flow cytometry, and western blotting to assess the expression of p-PI3K, PI3K, p-Akt, Akt, and VEGF. Compared with rats that underwent sham operation, rats with brain HI damage showed remarkably increased neurological deficits, reduced right blood flow volume, elevated blood viscosity and haematocrit, and aggravated cell damage and apoptosis; these injuries were significantly improved by curcumin pretreatment. Meanwhile, brain HI damage induced the overexpression of p-PI3K, p-Akt, and VEGF, while curcumin pretreatment inhibited the expression of these proteins. In addition, IGF-1 treatment rescued the curcumin-induced down-regulated expression of p-PI3K, p-Akt, and VEGF, and VEGF overexpression counteracted the inhibitory effect of curcumin on brain HI damage. Overall, pretreatment with curcumin protected against brain HI damage by targeting VEGF via the PI3K/Akt signaling pathway in neonatal rats.