• Journal of Life Science
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• v.17 no.7 s.87
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• pp.1019-1022
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• 2007

Thrombolytic therapy with tissue plasminogen activator (tPA) can improve the clinical outcome of ischemic stroke patients. However, its clinical application is limited by narrow therapeutic time windows and elevated risks of cerebral hemorrhage and brain injury. In part, these effects of tPA has been related to matrix metalloproteinase-9 (MMP-9) dysregulation. Here, we investigate that the effects of alteplase (tPA with short half-life) and pamiteplase (a modified tPA with long half-life) on the MMP-9 regulation in neurovascualr unit. The total levels of MMP-2 and MMP-9 in neuronal cells are lower than astrocytes. Alteplase (1-10 ${\mu}g/ml$) induced upregulation of MMP-2 and MMP-9 in rat cortical neurons and astrocytes, respectively. Whereas pamiteplase in a wide range of dose did not affect the MMP-2 and MMP-9 responses in both of cells. These results suggest that pamiteplase with long half-life can be provided as a agent that overcome the side effects of alteplase.

• The Journal of Korean Medicine
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• v.26 no.1 s.61
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• pp.174-186
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• 2005

Objectives : The water extract of Samul-tang (SMT) has traditionally been used for treatment of ischemic heart and brain damage in oriental medicine. However, little is known about the mechanism by which the water extract of SMT rescues cells from these damages. Methods: This study was designed to investigate the protective mechanisms of SMT on oxidative stress-induced toxicity in H9c2 cardiomyoblast cells. Treatment with $H_2O_2$ markedly induced death of H9c2 cardiomyoblast cells in a dose-dependent manner. Results: The characteristics of H20z-induced death of H9c2 showed apparent apoptotic features such as DNA fragmentation and morphological change. However, SMT significantly reduced both H202-induced cell death and morphological change. The decrease of Bc-2 expression by High were inhibited by SMT. In addition, the increase of Bax expression was also inhibited by SMT. The cotreatment of SMT and $H_2O_2$ in H9c2 cells also induced the phosphorylation of ERK in a time-dependent manner. Moreover, PD98059, a specific inhibitor of ERK1/2 attenuated the protective effects of SMT on $H_2O_2-induced$ toxicity in H9c2 cardiomyoblast cells. These results suggest that both ERK1/2 signaling pathways play important roles in the protective effects of SMT on $H_2O_2-induced$ apoptotic death of H9c2 cells. Also, the expression profile of proteins in $H_2O_2$ cardiomyoblast cells were screened by using two-dimensional (2-D) gel electrophoresis. Among 300 spots resolved in 2-D gels, the comparison of control versus apoptosis cells revealed that signal intensity of 17 spots increased and 11 spots decreased. Conclusions: Taken together, this study suggests that the protectiw effects of the water extract of SMT against oxidative damages may be mediated by the modulation of Bc1-2 and Bax expression via the regulation of the ERK signaling pathway.

• Korean Journal of Acupuncture
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• v.23 no.3
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• pp.81-98
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• 2006

Objectives : Acupuncture using a tonification or sedation techniques method is used as a controlling the medication for an early stroke in the Korean medicine. LR3 has indicatons of headache, vertigo, facial paralysis, apoplexy, epiepsy as the source acupoint of a liver meridian. So this study is aims to investigate the anti-apoptotic and neuroprotective effects of acupuncture on the focal ischemia induced by intraluminal filament insertion in rats. Methods : The focal ischemia was induced by intraluminal filament insertion into middle cerebral artery. The animals were divided into seven groups (n=8 in each group) : Normal, intactness group; Conrol group, no therapy group after being ischemia induced; MA-l, acupuncture perpendicularly without Tonification or Sedation techniques at LR3 after being ischemia induced; MA-2, acupuncture obliquely towards the knee at LR3 after being ischemia induced; MA-3, acupuncture obliquely towards the toe at LR3 after being ischemia induced; MA-4, acupuncture obliquely towards the knee and rotate 9 times in a clockwise direction at LR3 after being ischemia induced; MA-5, acupuncture obliquely towards the toe and rotate 6 times in a counterclockwise direction at LR3 after being ischemia induced. The anti-apoptotic and neuroprotective effects of Acupuncture techniques of tonification or sedation at LR3 are observed by mGluR5, Bax, Cresyl violet, ChAT-stain and NGF. Results : The intensity of mGluR5 and the density of ChAT was increased in MA-1 group. The intensity of Bax was decreased in MA-3, MA-4 group. The density of neurons stained by Cresyl violet and ChAT was increased in MA-2, MA-3, MA-4, MA-5 group. The density of neurons stained by NGF was only increased in MA-4 group. Conclusions : Our study suggests that acupuncture perpendicularly without Tonification or Sedation techniques and obliquely towards the knee and rotate 9 times in a clockwise direction(Tonifying technique) at LR3 after being ischemia induced at LR3 shows anti-apoptotic and neuroprotective effects on cholinergic neuron in focal cerebral ischemia of the stroke in rats.

• Korean Journal of Acupuncture
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• v.24 no.3
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• pp.205-221
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• 2007

Objectives : Aims of this study is to investigate the effects of $LU8{\cdot}KI7$ in rat induced by experimental focal ischemia. Materials and methods : The focal ischemia was induced by intraluminal filament insertion into middle cerebral artery. The groups divided into 6groups, control; no therapy group after ischemia-induced, AT1; acupuncture therapy group at $LU8{\cdot}KI7$ after ischemia-induced, AT2; acupuncture therapy at $LU8{\cdot}KI7$ bilaterally and the needle was twirled and rotated forward with the thumb of the right hand 9times, AT3; acupuncture therapy at $LU8{\cdot}KI7$ bilaterally and the needle was twirled and rotated forward with the forefinger of the right hand 9times, AT4; acupuncture therapy at$LU8{\cdot}KI7$ bilaterally and the needle was inserted to the direction following the flowing route of the meridian(digital direction), AT5; acupuncture therapy at $LU8{\cdot}KI7$ bilaterally, the needle was inserted to the direction following the flowing route of the meridian(digital direction) and the needle was twirled and rotated forward with the thumb of the right hand 9times. Acupuncture therapy was carried out 7times during 2weeks after focal ischemia-induced. The anti-apoptotic and neuroprotective effects of acupuncture are observed by Bax, Bcl-2, mGluR5, cytochrome c, Cresyl violet and ChAT-stain. Results : The intensity of Bax was decreased in AC1, AC4, AC5 group, was increased in AC2, AC3 group. The intensity of Bcl-2 was increased in AC2, AC3, AC4, AC5 group. The intensity of mGluR5 was decreased in AC1 group, was increased in AC4, AC5 group. The intensity of Cytochrome c was increased in ACI, AC2 group, was decreased in AC4, AC5 group. The density of neurons stained by Cresyl violet was increased in all group without control group. The density of ChAT was increased in AC2, ACS group. Conclusions : Our study suggests that AC5 group show anti-apoptotic and neuroprotective effects on cholinergic neuron in focal cerebral ischemia of the stroke in rats.

• Journal of Ginseng Research
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• v.46 no.4
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• pp.515-525
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• 2022

Background: The incidence of ischemic cerebrovascular disease is increasing in recent years and has been one of the leading causes of neurological dysfunction and death. Ginsenoside Rg1 has been found to protect against neuronal damage in many neurodegenerative diseases. However, the effect and mechanism by which Rg1 protects against cerebral ischemia-reperfusion injury (CIRI) are not fully understood. Here, we report the neuroprotective effects of Rg1 treatment on CIRI and its possible mechanisms in mice. Methods: A bilateral common carotid artery ligation was used to establish a chronic CIRI model in mice. HT22 cells were treated with Rg1 after OGD/R to study its effect on [Ca²⁺]_i. The open-field test and poleclimbing experiment were used to detect behavioral injury. The laser speckle blood flowmeter was used to measure brain blood flow. The Nissl and H&E staining were used to examine the neuronal damage. The Western blotting was used to examine MAP2, PSD95, Tau, p-Tau, NOX2, PLC, p-PLC, CN, NFAT1, and NLRP1 expression. Calcium imaging was used to test the level of [Ca²⁺]_i. Results: Rg1 treatment significantly improved cerebral blood flow, locomotion, and limb coordination, reduced ROS production, increased MAP2 and PSD95 expression, and decreased p-Tau, NOX2, p-PLC, CN, NFAT1, and NLRP1 expression. Calcium imaging results showed that Rg1 could inhibit calcium overload and resist the imbalance of calcium homeostasis after OGD/R in HT22 cells. Conclusion: Rg1 plays a neuroprotective role in attenuating CIRI by inhibiting oxidative stress, calcium overload, and neuroinflammation.

• Korean Journal of Acupuncture
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• v.40 no.3
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• pp.79-89
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• 2023

Objectives : The purpose of this study is to investigate various application methods of focused ultrasound and apply them to clinical use in Korean medicine. Methods : Search was performed using the search engines of electronic databases, including PubMed, ScienceDirect, Cumulative Index to Nursing and Allied Health Literature (CINAHL), ScienceON, Oriental Medicine Advanced Searching Integrated System (OASIS), China National Knowledge Infrastructure (CNKI), Wanfang Data, Japan Science Technology Information Aggregator, Electronic (J-STAGE) and Citation Information by NII (CiNii), from inception to July 2023 without language limitation. Inclusion criteria were clinical studies including randomized controlled trials (RCTs), and animal experimental studies related with focused ultrasound treatments for acupoints or meridian sinews. Results : Total 17 papers, 7 for RCT, 6 for in vivo animal studies, and other experimental studies, were finally selected. Indications used in studies were shoulder pain, back pain, chronic back pain, and degenerative knee arthritis. In experimental studies, studies on animal models of hypoxic ischemic brain damage and hyperlipidemia were also conducted. As for the acupoints, LR3, LI4, and ST36 were used in clinical studies and, in animal experimental studies, GV20, KI1, and ST36 were used. As for the dose, 4 studies below 3 W/cm² and 3 studies in the range of 0.625 to 5 W/cm² in clinical studies, and all studies did not exceed 5 W/cm². In animal experimental studies, 0.5 W/cm², 2 W/cm², 7.5 WW/cm², 15 W/cm², 10~20 W/cm² were used. In all three studies describing the penetration depth during irradiation, it was less than 1 cm. Conclusions : We suggest that focused ultrasound is an appropriate treatment tool for stimulating the acupoints to transfer heat energy. Future studies with rigorous and well-designed RCTs for various diseases will be required to ascertain the focused ultrasound stimulate acupoints or meridian sinews.

• The Korean Journal of Pharmacology
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• v.18 no.2
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• pp.1-14
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• 1982

The effects of xanthine-xanthine oxidase reaction on brain microsomal $Na^+-K^+-ATPase$ activity were studied to see possible involvement of oxygen free radicals in pathologic change occurring in ischemic state of CNS accompanied by cerebral vascular occlusion or impact injury. When microsomal fraction was incubated with xanthine ana xanthine oxidase, $Na^+-K^+-ATPase$ activity of the fraction was markedly inactivated (80% inactivation) whereas btssl $Mg^{++}-ATPase$ was much less sensitive (less than 10% inactivation) compared to that of $Na^+-K^+-ATPase$. The inactivation was observed only in the presence of both xanthine and xanthine oxidase, not either of them alone, and the extent of inactivation was dependent on the concentration of xanthine. In an attempt to determine which of the oxygen species was responsible for the inactivation, the ability of various scavengers to overcome the inactivation was tested. Superoxide dismutase, catalase and 1,4-diazabicyclo(2,2,2)octane were shown to reverse the inactivation of the ATPase in dose-dependent manner. In contrast, mannitol as well as other $OH{\cdot}$quenchers were ineffective in limiting oxygen radical-induced inactivation. Thus $O_{\bar{2}}{\cdot},\;H_2O_2$ and $^1O_2$ were implicated to be mediators involved in the inactivation. Since oxygen radicals are suspected as being a cause of the peroxidative damaging process in train ischemia, the ATPase inactivation by oxygen radicals may be a possible contributing factor which gives rise to functional derangement of nerve cells observed in the pathologic process.

• The Journal of Korean Medicine
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• v.16 no.2 s.30
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• pp.17-35
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• 1995

Clinical observation was made on 161 cases of CVA that were confirmed through brain CT, MRI scan and clinical observation. They were hospitalized in the oriental medical hospital of Kyung-Won University from January to December in 1994. 1. The CVA cases were classified into the following kinds: cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage(SAH), transient ischemic attack, hypertensive encephalopathy, and the greatest in number among them were the cases of cerebral infarction. 2. The frequency of strokes was much the same between male and female cases and most cases were over 50 of age. 3. In the case of cerebral infarction the place of the most frequent occurrences was in the MCA territory, and as for cerebral hemorrhage, in the basal ganglia area. 4. The most ordinary preceding disease was hypertension. The next was diabetes mellitus. 5. Generally it is thought that CVA occurs frequently in winter. But on the contrary this study of observation confirmed that it occurs mostly in summer. 6. The predisposing factors of cerebral infarction were usually initiated during the time of resting and sleeping and those of cerebral hemorrhage chiefly during the time of exercising. 7. As concerns the course of hospitalization, most patients passed through western medical hospitals or oriental medical hospitals. 8. For the patients the condition of whose consciousness was bad at the time of admission, the prognosis in most cases was bad. 9. The common symptoms were motor disability and verbal disturbance. 10. With regard to cerebral infarction, the average time to start physical theraphy was 11.4 days and with cerebral hemorrhage 22.7 days after stroke. 11. The duration of hospitalization was in most cases more than one month. 12. The main complication was urinary tract infection. The next was pneumonia. 13. At the time of admission to hospital, the blood pressure in most cases was high, but it well controlled at the time of discharge. 14. Most cases were given simultaneous treatment in both ways of western and oriental medicine.

• The Journal of Korean Medicine
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• v.18 no.1
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• pp.5-24
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• 1997

Clinical observation was made on 226 cases of CVA that were confirmed through brain CT, MRI scan and clinical observation. They were hospitalized in the oriental medical hospital of Kyung-Won University from January to December in 1995. 1. The CVA cases were classified into the following kinds: cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage(SAH), transient ischemic attack, and the greatest in number among them were the cases of cerebral infarction. 2. The frequency of strokes was much the same between male and female cases and most cases were over 50 of age. 3. In the case of cerebral infarction the place of the most frequent occurrences was in the MCA territory, and as for cerebral hemorrhage, in the basal ganglia area. 4. The most ordinary preceding disease was hypertension. The next was diabetes mellitus. 5. Generally it is thought that CVA occurs frequently in winter. But on the contrary this study of observation confirmed that it occurs mostly in spring and summer. 6. The predisposing factors of cerebral infarction were usually initiated during the time of resting and sleeping and those of cerebral hemorrhage chiefly during the time of exercising. 7. As concerns the course of hospitalization, most patients passed through vestern medical hospitals or oriental medical hospitals. 8. For the patients the condition of whose consciousness was bad at the time of admission. the prognosis in most cases was bad. 9. The common symptoms were motor disability and verbal disturbance. 10. With regard to cerebral infarction, the average time to start physical theraphy was 6.4 days and with cerebral hemorrhage 9.7 days after stroke. 11. The duration of hospitalization was in most cases more than one month. 12. The main complication was urinary tract infection. 13. At the time of admission to hospital, the blood pressure in most cases was high, but it well controlled at the time of discharge. 14. Most cases were given simultaneous treatment in both ways of western and oriental medicine.

• Journal of Haehwa Medicine
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• v.9 no.1
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• pp.387-397
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• 2000

Background : Intravascular Laser Irrardiation of Blood(ILIB) is used in disorder of cerebral and peripheral blood circulation, dysfunction of brain, atherosclerosis etc., but there are little study about ILIB in oriental medicine. We wished to assess the efficacy of ILIB for the treatment of cerebral infarction. Method : The study group comprised 40 patients who arrived at hospital during 48 hours after attack. All patient were divided into two group. The control group was treated with Uhuangcheongsimhuan(牛黃淸心丸), Seonghyangjeonggisan(星香正氣散), acupuncture therapy only, while the ILIB group was treated with above therapy plus 5 days of irradiation of He-Ne Laser(1.8~2.5mW, 50min. per day). In rat model of middle cerebral artery(MCA) occlusion, the control group was not treated, while the ILIB group was treated with irradiation of He-Ne Laser(1.8~2.5mW, 24sec.). Result : 1. Symptom improve scores did not showed significant difference between control and ILIB group. 2. Vasoreactivity of carotid siphon did not showed significant difference between control and ILIB group. 3. Vasoreactivity of radial artery did not showed significant difference between control and ILIB group. 4. PT a-PTT did not showed significant changes between before and after treatment in both group. Fibrinogen significantly increased after treatment in ILIB group(p<0.05)), but it was in normal degree. 5. ILIB showed a significant decrease of brain ischemic area and edema in rat model of middle cerebral artery(MCA) occlusion. Conclusion : These findings suggest that additional treatment of ILIB is not more useful than traditional therapy only in acute cerebral infarction. But ILIB showed potential effect in rat model of MCA occlusion. So further investigation will be necessary.