• Biomolecules & Therapeutics
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• 제28권6호
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• pp.512-518
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• 2020

Stroke is a leading cause of long-term disability in ischemic survivors who are suffering from motor, cognitive, and memory impairment. Previously, we have reported suppressing LPA₅ activity with its specific antagonist can attenuate acute brain injuries after ischemic stroke. However, it is unclear whether suppressing LPA₅ activity can also attenuate chronic brain injuries after ischemic stroke. Here, we explored whether effects of LPA₅ antagonist, TCLPA5, could persist a longer time after brain ischemic stroke using a mouse model challenged with tMCAO. TCLPA5 was administered to mice every day for 3 days, starting from the time immediately after reperfusion. TCLPA5 administration improved neurological function up to 21 days after tMCAO challenge. It also reduced brain tissue loss and cell apoptosis in mice at 21 days after tMCAO challenge. Such long-term neuroprotection of TCLPA5 was associated with enhanced neurogenesis and angiogenesis in post-ischemic brain, along with upregulated expression levels of vascular endothelial growth factor. Collectively, results of the current study indicates that suppressing LPA₅ activity can provide long-term neuroprotection to mice with brain ischemic stroke.

• Biomolecules & Therapeutics
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• 제32권3호
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• pp.319-328
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• 2024

Lysophosphatidic acid receptor 1 (LPA₁) plays a critical role in brain injury following a transient brain ischemic stroke. However, its role in permanent brain ischemic stroke remains unknown. To address this, we investigated whether LPA₁ could contribute to brain injury of mice challenged by permanent middle cerebral artery occlusion (pMCAO). A selective LPA₁ antagonist (AM152) was used as a pharmacological tool for this investigation. When AM152 was given to pMCAO-challenged mice one hour after occlusion, pMCAO-induced brain damage such as brain infarction, functional neurological deficits, apoptosis, and blood-brain barrier disruption was significantly attenuated. Histological analyses demonstrated that AM152 administration attenuated microglial activation and proliferation in injured brain after pMCAO challenge. AM152 administration also attenuated abnormal neuroinflammatory responses by decreasing expression levels of pro-inflammatory cytokines while increasing expression levels of anti-inflammatory cytokines in the injured brain. As underlying effector pathways, NF-κB, MAPKs (ERK1/2, p38, and JNKs), and PI3K/Akt were found to be involved in LPA₁-dependent pathogenesis. Collectively, these results demonstrate that LPA₁ can contribute to brain injury by permanent ischemic stroke, along with relevant pathogenic events in an injured brain.

• Nuclear Medicine and Molecular Imaging
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• 제41권2호
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• pp.91-96
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• 2007

The measurement of pathologically low levels of tissue $pO_2$ is an important diagnostic goal for determining the prognosis of many clinically important diseases including cardiovascular insufficiency, stroke and cancer. The target tissues nowaday have mostly been tumors or the myocardium, with less attention centered on the brain. Radiolabelled nitroimidazole or derivatives may be useful in identifying the hypoxic cells in cerebrovascular disease or traumatic brain injury, and hypoxic-ischemic encephalopathy. In acute stroke, the target of therapy is the severely hypoxic but salvageable tissue. $^{18}F-MISO$ PET and $^{99}mTc-EC-metronidazole$ SPECT in patients with acute ischemic stroke identified hypoxic tissues and ischemic penumbra, and predicted its outcome. A study using $^{123}I-IAZA$ in patient with closed head injury detected the hypoxic tissues after head injury. Up till now these radiopharmaceuticals have drawbacks due to its relatively low concentration with hypoxic tissues associated with/without low blood-brain barrier permeability and the necessity to wait a long time to achieve acceptable target to background ratios for imaging in acute ischemic stroke. It is needed to develop new hypoxic marker exhibiting more rapid localization in the hypoxic region in the brain. And then, the hypoxic brain imaging with imidazoles or non-imidazoles may be very useful in detecting the hypoxic tissues, determining therapeutic strategies and developing therapeutic drugs in several neurological disease, especially, in acute ischemic stroke.

• Biomolecules & Therapeutics
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• 제30권1호
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• pp.55-63
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• 2022

Oleanolic acid (OA), a natural pentacyclic triterpenoid, has been reported to exert protective effects against several neurological diseases through its anti-oxidative and anti-inflammatory activities. The goal of the present study was to evaluate the therapeutic potential of OA against acute and chronic brain injuries after ischemic stroke using a mouse model of transient middle cerebral artery occlusion (tMCAO, MCAO/reperfusion). OA administration immediately after reperfusion significantly attenuated acute brain injuries including brain infarction, functional neurological deficits, and neuronal apoptosis. Moreover, delayed administration of OA (at 3 h after reperfusion) attenuated brain infarction and improved functional neurological deficits during the acute phase. Such neuroprotective effects were associated with attenuation of microglial activation and lipid peroxidation in the injured brain after the tMCAO challenge. OA also attenuated NLRP3 inflammasome activation in activated microglia during the acute phase. In addition, daily administration of OA for 7 days starting from either immediately after reperfusion or 1 day after reperfusion significantly improved functional neurological deficits and attenuated brain tissue loss up to 21 days after the tMCAO challenge; these findings supported therapeutic effects of OA against ischemic stroke-induced chronic brain injury. Together, these findings showed that OA exerted neuroprotective effects against both acute and chronic brain injuries after tMCAO challenge, suggesting that OA is a potential therapeutic agent to treat ischemic stroke.

• 대한한방내과학회지
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• 제21권2호
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• pp.341-348
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• 2000

I have treated one ischemic stroke patient in acute stage with Seonghyangjeonggi-san, and observed remarkable reduction of the size ischemic portion in brain CT, notable improved motor power of patient. So I report this case of stroke patint. The ischemic penumbra, simply stated, is the part of the brain that is sandwiched brain regions committed to die and those that receive enough blood to communicate. Therefore, it is ischemic brain tissue that has just enough to communicte and function. The life expectancy of the penumbrais short. Although the penumbra is an elegant concept, in practice, it has been a difficult one to exploit. Up to now, a lot of research worker have tried to develop the method to make a accurate diagnosis. and then we know that PET and Xenon CT is available for the diagnosis for the ischemic penumbra. But those are not perfect to diagnose of penumbra. The case in my case report was confirmed as ischemic penumbra with CT. I know that CT is not prefect to diagnose penumbra, but I just want to raise the interest in penumbra of oriental medicine researcher and my report will be benificial to the penumbra researcher.

• 대한핵의학회지
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• 제35권6호
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• pp.343-351
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• 2001

Cerebral post-ischemic hyperperfusion has been observed at the acute and subacute periods of ischemic stroke. In the animal stroke model, early post-ischemic hyperperfusion is the mark of recanalization of the occluded artery with reperfusion. In the PET studios of both humans and experimental animals, early post-ischemic hyperperfusion is not a key factor in the development of tissue infarction and indicates the spontaneous reperfusion of the ischemic brain tissue without late infarction or with small infarction. But late post-ischemic hyperperfusion shows the worse prognosis with reperfusion injury associated with brain tissue necrosis. Early post-ischemic hyperperfusion defined by PET and SPECT may be useful in predicting the prognosis of ischemic stroke and the effect of thrombolytic therapy.

• Toxicological Research
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• 제29권3호
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• pp.157-164
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• 2013

Although stroke is one of the leading causes of death and disability worldwide, preventive or therapeutic options are still limited. Therefore, a better understanding of the pathophysiological characteristics of this life-threatening disease is urgently needed. The incidence and prevalence of ischemic stroke are increased by exposure to certain types of xenobiotics, including heavy metals, suggesting the possible toxicological contribution of these compounds to the onset or aggravation of stroke. Among the potential targets, we have focused on alterations to cerebral endothelial cells (CECs), which play important roles in maintaining the functional integrity of brain tissue.

• 대한한의학회지
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• 제31권5호
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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.

• 대한본초학회지
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• 제25권2호
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• pp.71-79
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• 2010

Objectives : In this study, the neuroprotective effects of modified Boyanghwano-Tang (mBHT) and the major medicinal plants, Astragali Radix(AR) and Salviae Miltiorrhizae Radix(SMR) were investigated in transient middle cerebral artery occlusion (tMCAO)-induced ischemic stroke of rats. Methods : mBHT(400 mg/kg) and AR(154 mg/kg) or SMR(62 mg/kg) water extract orally injected in rats after 90 min occlusion of MCA and then allow reperfusion to 24 h. Brain infarction was measured by TTC staining and the expressions of NOS isoforms and apoptotic molecules were determined in ischemic brain by Western blot. Results : The results showed that mBHT has stronger neuropreotective property through inhibitions of the PARP cleaved and caspase-3 activation in ischemic rats, and could reduced infarction volumes comparison of those of AR or SMR, respectively. While, AR extract has an angiogenic property through increasing the expressions of eNOS and VEGF, and SMR extract has a strong anti-inflammatory effects through inhibition of iNOS expression in ischemic brains. Conclusions : These results suggest that mBHT has multifactorial therapeutic advantages through anti-apoptosis, anti-inflammation and angiogenesis for ischemic stroke based on a synergistic combination of ingradients rather than monotherapy.

• Journal of Acupuncture Research
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• 제21권1호
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• pp.111-118
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• 2004

Background and purpose: Opposing-needling technique involves selecting acupoints at unaffected limb. The aim of this study was to evaluate the effect of LI4-LI11 electrical acupuncture at unaffected limb on the cerebral blood flow in ischemic stroke patients using SPECT Methods: We selected 9 ischemic stroke patients. Baseline brain SPECT was done with triple head gamma camera(MultiSPECT3, Siemens, USA) after intravenous administration of 925 MBq of Tc-99m ECD). Fifteen-minute electro-acupuncture at Hapgok(LI 4) and Gokji(LI 11) were applied on unaffected upper limb of subjects. The same dose of Tc-99m ECD was injected during the electro-acupuncture, and the second SPECT images were obtained. Using the computer software(ICON 7.1, Siemens, USA), 3 SPECT slices(upper, middle, lower) surrounding the brain lesion were selected and each slice was divided by 10-16 brain regions. Asymmetry indexes were analyzed in each brain region. We regarded$\geq$10% changes of asymmetry index between before and after electro-acupuncture as significance. Results: Seven Patients(77.8%) had significantly increased perfusion and 2(22.2%) didn't show increased perfusion in post-acupuncture scans compared to pre-acupuncture scans(baseline). The regions of CBF improvement were mostly frontal lobes and anterior temporal lobes. Conclusions: This study demonstrated that LI4-LI11 electro-acupuncture at unaffected limb increased regional cerebral blood perfusion to the corresponding brain areas in ischemic stroke patients.