• The Journal of Internal Korean Medicine
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• v.21 no.1
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• pp.116-125
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• 2000

Objectives : The aim of this study is to investigate that Sunghyangjeongki-San which has been frequently medicated in the early stage of stroke can protect against ischemic damage in rat brain Methods : Extracellular levels of amino acids(glutamate, aspartate, GABA, glycine, taurine, tyrosine, alanine), organic acids(pyruvate, lactate), and cerebral infarction volume were measured at the striatum of rats subjected to permanant focal cerebral ischemia induced by 2 hours of middle cerebral artery occiusion(MCAO). Rats were orally administered with Sunghyangjeongki-San at 30mins before MCAO and the microdialysate was collected by intracerebral microdialysis three times before MCAO and six times after MCAO at 20mins interval and analyzed by HPLC. After a microdialysis study, the brain was sliced and stained with cresyl violet buffer for the measurement of cerebral infarcted area and volume by image analyzer system Results : The concentrations of glutamate, aspartate, and tyrosine known as excitatory neurotransmitters were significantly decreased in Sunghyangjeongki-San group compared with control group, The concentrations of GABA, glycine, taurine and alanine known as inhibitory neurotransmitters were significantly increased in Sunghyangjeongki-San group compared with control group. The concentrations of pyruvate and lactate showed little significant change in Sunghyangjeongki-San group compared with control group. The measurement of cerebral infarcted area and volume by image analyzer system were significantly decreased in Sunghyangjeongki-San group compared with control group. Conclusions : Sunghyangjeongki-San can affect on protecting against cerebral ischemia by regulating extracellular levels of excitatory and inhibitory amino acid neurotransmitters and improve the conditions of the patients in the early stage of stroke.

• 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.

• 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.

• Proceedings of the Korean Society of Developmental Biology Conference
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• 2003.10a
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• pp.69-69
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• 2003

Neuroprotective strategies have been appeared to be effective in a variety of stroke models. One of the major focuses has been related to the activities of estrogen. $17\beta$-estradiol valerate(EV) has been reported to exert neuroprotective effects when administered before an ischemic insult. The purpose of this study was to determine whether EV can protect against brain injury via estrogen receptor. Chronic and acute pretreatment can reduce the ischemic damage of focal cerebral ischemia in OVX rat, indicating that EV may be a new therapeutic class of drugs to prevent neuronal damage associated with cerebral ischemia. RNAs were extracted from the hippocampus of ovariectomized female rat with or without EV. Differential gene expression profiles were revealed(Bone morphogenetic protein type 1A receptor, Protein disulphide isomerase, cytochrome bc-1 complex core P, thiol-specific antioxidant protein). RT-PCR and in situ hybridization were used to validate the relative expression pattern obtained by the cDNA array. This Study was supported by the Korea Science and Engineering Foundation(KOSEF) through the Biohealth Products Research Center(BPRC), Inje University, Korea

• The Korea Journal of Herbology
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• v.29 no.6
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• pp.85-93
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• 2014

Objectives : We compared with the effects of different parts (root head, root body and hairy root) of Angelica gigas Nakai (Angelicae Gigantis Radix, AG) with on middle cerebral artery occlusion(MCAO)-induced ischemic rats, and on LPS-induced inflammatory response in BV2 microglia. Methods : The 30% ethanol and water extracts of different parts of AG were prepared. Each extract (50 and 100 mg/kg) was administrated intraperitoneally once in MCAO-induced ischemic rats. We measured infarction volumes by TTC staining, and investigated the expression of iNOS, Bax, Bcl-2 and caspase-3 by Western blot. BV2 cells were treated with each extract for 30 min, and then stimulated with LPS. The levels of NO was measured by Griess assay. The expression of iNOS, Cox-2 and proinflammatory cytokines ($TNF-{\alpha}$, $IL-1{\beta}$, and IL-6) were determined RT-PCR and Western blot. The phosphorylation of ERK1/2 and JNK MAPK was determined by Western blot. Results : Among different parts of AG, the 30% ethanol and water extracts of hairy root significantly decreased infarction volume in ischemic brains and inhibited the expression of iNOS, bax and caspase-3. The extracts of hairy root significantly inhibited LPS-induced production of NO, $TNF-{\alpha}$ and IL-6 in BV2 cells, and suppressed the expression of iNOS and COX-2. The hairy root extracts attenuated LPS-induced phosphorylation of ERK1/2 and JNK MAPK in BV2 cells. Conclusions : Our results indicate that the root hairy of AG has a good neuroprotective and anti-inflammatory effects in ischemic stroke compared to other parts.

• Journal of Physiology & Pathology in Korean Medicine
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• v.27 no.4
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• pp.446-452
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• 2013

This study was designed to investigate the effects of Angelicae Gigantis and Cynanchum wilfordii Hemsley extract (AAC) on the changes of regional cerebral blood flow (rCBF) and mean arterial blood pressure (MABP) in normal rats, and in the rats with cerebral ischemia induced by middle cerebral artery occlusion, and further to determine the mechanisms. The results were as follows. AAC significantly increased rCBF but significantly decreased MABP in a dose-dependent manner in normal rats. The increase of AAC-induced rCBF was significantly inhibited by pretreatment with methylene blue (0.01 mg/kg, i.p.), an inhibitor of guanylate cyclase, and AAC-induced MABP was decreased by pretreatment with methylene blue. In cerebral ischemics, rCBF was stably improved by AAC (10 mg/kg, i.p.) during the period of cerebral reperfusion, which was contrasted with the findings of rapid and marked increase in the control group. These results suggest that AAC can increase rCBF in the normal state, as well as improve the stability of rCBF in cerebral ischemic state.

• The Journal of Internal Korean Medicine
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• v.22 no.3
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• pp.341-351
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• 2001

Object: Acori graminei rhizoma(AGR) extract is clinically used to treat the cerebral ischemia in Korea. The present study was undertaken to study the neuroprotective effect of AGR extract in middle cerebral artery occlusion(MCAO) rats. Methods: Changes of extracellular levels of glutamate, aspartate, GABA, glycine, taurine, tyrosine, alanine in striatum were collected at 20 minutes interval by in vivo microdialysis and then analyzed by HPLC(high performance liquid chromatography) in rats subjected to permanent focal cerebral ischemia induced by 2 hours of MCAO. AGR extract was orally administrated before MCAO. Different animals were used for measurement of cerebral infarction volume induced by 24 hours of MCAO with TTC staining and image analysis. Result : The infarction volume was decreased and focal cerebral ischemia - induced increase of extracellular glutamate, aspartate, and tyrosine were inhibited after the treatment of AGR extract. On the other hand, the increase of glycine and alanine not but GABA and taurine were enhenced after the treatment of AGR extract. Conclusion: These results suggest that AGR extract can playa role in protecting against cerebral ischemia by regulating extracellular levels of excitatory and inhibitory amino acid neurotransmitters.

• Parasites, Hosts and Diseases
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• v.58 no.4
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• pp.461-466
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• 2020

Toxoplasma gondii is an obligate intracellular protozoan parasite that can invade various organs in the host body, including the central nervous system. Chronic intracranial T. gondii is known to be associated with neuroprotection against neurodegenerative diseases through interaction with host brain cells in various ways. The present study investigated the neuroprotective effects of chronic T. gondii infection in mice with cerebral ischemia experimentally produced by middle cerebral artery occlusion (MCAO) surgery. The neurobehavioral effects of cerebral ischemia were assessed by measurement of Garcia score and Rotarod behavior tests. The volume of brain ischemia was measured by triphenyltetrazolium chloride staining. The expression levels of related genes and proteins were determined. After cerebral ischemia, corrected infarction volume was significantly reduced in T. gondii infected mice, and their neurobehavioral function was significantly better than that of the uninfection control group. Chronic T. gondii infection induced the expression of hypoxia-inducible factor 1-alpha (HIF-1α) in the brain before MCAO. T. gondii infection also increased the expression of vascular endothelial growth factor after the cerebral ischemia. It is suggested that chronic intracerebral infection of T. gondii may be a potential preconditioning strategy to reduce neural deficits associated with cerebral ischemia and induce brain ischemic tolerance through the regulation of HIF-1α expression.

• Korean Journal of Acupuncture
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• v.19 no.2
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• pp.63-78
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• 2002

Kupunggibodan(KU), Gamisamul-tang(GA) and Whangryunhaedok-tang(WH) are clinically the most popular prescriptions as an herbal medicine in the treatment of ischemia. In order to compare and evaluate their protective effects on the ischema-induced cognitive deficits by middle cerebral artery occlusion (MCAO), we examined its ability to improve ischemia-induced cell loss and impairements of learning and memory in the Morris water maze and eight-arm radial arm maze. Focal cerebral ischemia produced a marked cell loss, decrease in acetylcholinesterase(AchE) reactivity in the hippocampus, and learning and memory deficits in two behavioral tasks. Pretreatment with WH (100 mg/kg, p.o.) produced a substantial increase in acquisition in the Morris water maze. Pretreatment with KU increased the perfomance of the resention test in the Morris water maze. WH, KU and GA caused a significant improvement in choice accuracy in radial arm maze test. WH was superior to KU and GA in perfomance of the radial arm maze test. Consistent with behavioral data, staining with cresyl violet showed that pretreatments with WH, but not KU and GA significantly recovered the ischemia-induced cell loss in the hippcampal CA1 area. In addition, pretreatments with WH and KU recovered the ischemia-induced reduction of AchE reactivity in the hippocampal CA1 area. These results demonstrated that KU, GA and WH have protective effects against ischimea-induced learning and memory impairments and that the efficacy was the order of WH>KU>GA in tratment of ischemia induced memory deficits. The present studies provide an evidence of KU, GA and WH as putative treatment of vascular dementia. Supported by a fund from the Ministry of Health and Welfare(HMP-00-OO-04-0004), and the Brain Korea 21 Project from Korean Ministry of Education, Korea.

• The Korea Journal of Herbology
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• v.32 no.1
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• pp.25-31
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• 2017

Objectives : Mori Radicis Cortex (MRC), the root epidermis of Morus alba L., has been traditionally used to treat lung-related diseases in Korean Medicine. The common of MRC is Mulberry bark Morus bark, and it's pharmaceutical properties and taste are known as sweet and cold, and it promotes urination and reduce edema by reducing heat from the lungs and soothe asthma. In the present study, anti-apoptotic mechanism of MRC in middle cerebral artery occlusion (MCAO) model in mice. Methods : Two-hundred grams of MRC was extracted with methanol at room temperature for 5 days, and this was repeated one time. After filtration, the methanol was removed using vacuum evaporator, then stored at $-20^{\circ}C$ until use. C57BL/6 male mice were housed in an environment with controlled humidity, temperature, and light cycle. In order to determine beneficial effects of MRC on ischemia induced brain damage, infarct volume, neurological deficit scores, activities of several apoptosis-related proteins such as caspase-8, -9, Bcl-xL in MCAO-induced brains of mice were analyzed. Mice in MRC-treated groups were orally administered 30, 100, or 300 mg/kg of body weight for three consecutive days before commencing the MCAO procedure. Results : Pre-treatment of MRC significantly reduced infarct volume in MCAO subjected mice applied with 300 mg/kg of MRC methanol extract, and MRC effectively inhibited Bcl-xL reduction and caspase-9 activation caused by MCAO-induced brain damage. Conclusions : MRC showed neuro-protective effects by regulating apoptosis-related protein signals, and it can be a potential candidate for the therapy of ischemia-induced brain damage.