• Journal of Ginseng Research
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• 제46권4호
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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.

• 대한본초학회지
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• 제32권1호
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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.

• 농업생명과학연구
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• 제46권6호
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• pp.137-146
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• 2012

본 연구는 중간대뇌동맥을 폐쇄한 대뇌허혈성 손상모델에서 ferulic acid에 의해 조절되는 HO-1과 HO-2의 발현에 관하여 조사하였다. 흰쥐(Sprague-Dawley, 수컷)에 ferulic acid (100 mg/kg) 또는 vehicle을 중간대뇌동맥폐쇄술(MCAO) 후 정맥으로 주사하였고 중간대뇌동맥폐쇄술(MCAO)을 실시한 24시간 후 대뇌피질의 조직을 적출하였다. Hematoxylin과 eosin 염색을 통하여 MCAO로 유도된 뇌 손상시 ferulic acid의 보호효과를 확인하였다. MCAO을 시행한 대뇌피질에서는 응축된 핵과 신경세포의 괴사 소견을 보였으나, ferulic acid 투여군에서는 이들 신경세포의 병변을 현저히 완화시켰다. HO-1과 HO-2의 RNA와 단백질 발현의 변화를 reverse-transcription PCR과 Western blot으로 분석하였다. HO-1 발현은 MCAO 후 vehicle 투여군에서 현저히 감소하였으나, MCAO 후 ferulic acid를 투여한 실험군에서는 이들 감소의 완화를 보였으며, MCAO를 시행하지 않은 실험군의 수준으로 유지되었다. 그러나, HO-2의 발현은 MCAO 후 vehicle 투여군과 ferulic acid 투여군에서 유의적인 차이는 관찰되지 않았고 MCAO를 시행하지 않은 실험군의 수준으로 유지되었다. 따라서, 본 연구의 결과는 허혈성 뇌 손상시 ferulic acid는 HO-1 발현을 조절하였으나, HO-2의 발현에는 영향을 미치지 못함을 확인하였다. 결론적으로, 허혈성 뇌손상시 ferulic acid는 HO-1의 발현을 조절하여 신경세포를 보호하는 역할을 수행한다는 사실을 확인하였다.

• Journal of Chest Surgery
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• 제30권8호
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• pp.752-759
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• 1997

복합 심장질환이나 대동맥궁 수술시 뇌손상을 보호하기 위하여 오래전부터 초저체온하 완전순환정지법 을 이용하고 있다. 수술후 뇌손상을 예방하기 위하여 여러 방법들을 이용하여 왔으며, 1994년이후 저자들은 뇌대사를 감시하기 위한 방법으로 수술중 뇌파감시를 하고 있다. 저자들은 심장수술실에 사용이 편리한 뇌 파 압축 스펙트럼 정렬(compressed spectral array; CSA) 시스템을 개발하여 이를 대동맥수술시 초저체온 및 설 전순환차단하에 뇌파감시에 적용하여 이의 유용성을 검증하고, 초저체온하 뇌파를 연속감시하여 뇌파가 소 실되고 다시 나타나는 온도를 확인하여 순환정지의 안전한 온도와 시간을 연구하였다. 급성 대동맥박리증 3 례와 대동맥궁 대동맥류 3례(2례는 가성)의 대동맥질환 환자를 연구대상으로 하였다. 직장과 식도체온을 연 속 감시하였으며,마취후 뇌파를 연속감시하였다. 대상환자들중 3례는 초저체온하 완전순환차단하에 수술을 하였으며, 3례는 초저체온하 선택적 뇌관류하에(500 700Ml분) 수술을 하였다. 환자의 체온을 하강하여 뇌 파가 소실된 후 약 3분 후에 순환정지나 선택적 뇌관류를 하였다. 뇌파가 소실된 체온은 직장\ulcorner온이 $16.1^{\circ}C-22.1^{\circ}C(평균:$ $18.4\pm2.0),$ 식도체온이 $12.7^{\circ}C~16.4^{\circ}C(평균:$ $14.7\pm1.6)였다.$ 완전순환차단 환자의 경우 뇌 허혈 시간은 각각 30, 36, 및 56분이었으며, 뇌관류 환자의 경우 각각 41, 56, 92분이었다. 수술중 뇌파가 다시 나 타난 시간 및 체온은(증례 3~6) 5~23분후에 직장체온이 $14.1^{\circ}C~20.3^{\circ}C,$ 식도체온이 $11.7^{\circ}C~15.4^{\circ}C에서$ 나타났다. 수술후 뇌손상의 증상은 없었으며,수술과 관련된 사망은 없었다. 이상의 결과로 식도체온이 $16^{\circ}C이하에서도$ 뇌파가 23분이내에 다시 나타난 것으로 보아 식도체온이 $15^{\circ}C이하는$ 되어야 약 30분간의 완전순환 차단에 안전하리라 생각되었으며, 대동맥 수술시 CSA를 이용한 뇌파감시는 전기뇌활동을 감시하는데 유용 한 방법으로 생각되었다.

• 대한한의학방제학회지
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• 제22권1호
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• pp.13-32
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• 2014

Objectives : Until now the study of Cnidii Rhizoma, hemorrhage, brain waves, such as ischemic brain injury, analgesic, effect overcome of the stress from pregnancy melanin formation and inhibiting effects skin whitening have been published regarding this article. Cnidii Rhizoma demonstrates its different abilities depending on the characteristics. This paper reported that effect of Cnidii Rhizoma in Dongeuibogam blended prescriptions as main medicine. In addition, by analyzing data, we studied about utilizing of Cnidii Rhizoma. Methods : Cnidii Rhizoma in Dongeuibogam Prescriptions as the main ingredient was built with database of 202 prescriptions. Thus analyzed data was summarized in detail.(Table-1) If there is no difference in the title of the prescription but in other case the configuration information is different, formulations 1 and 2 were divided by the table. Results : The following results were reached through investigations on the prescriptions usikng Cnidii Rhizoma as a key component. 1. Prescriptions taking Cnidii Rhizoma as a monarch drug are utilized for 40 therapeutic purposes. In particular, 12.3% of prescriptions appear in the chapter of head, and 10.8% of those appear in the chapter of women, and 9.4% of eye, 8.9% of child, 6.4% of wind disease respectively. 2. Prescriptions utilizing Cnidii Rhizoma as the main ingredient are used in the treatment of headache, dizziness and pregnancy hemorrhage fetal movement, premature birth and they are also used for treating 131 different types of disease. 3. The dosage of Cnidii Rhizoma in formulas is from 2pun(about 0.75g) to 5don(nearly 18.75g), however 1don(nearly 3.75g) has been taken the most for clinical application. 4. We find out that according to herbs or prescriptions, Cnidii Rhizoma has a variety of functions such as ascending & descending of energy. Samultang is the most useful base prescription which used the Cnidii Rhizoma as the main component. Conclusion : These results suggest that, Cnidii Rhizoma once-amount use (don nearly 3.75g) 4g in head, gynecology, ophthalmology, pediatrics and paralysis disease associated with oriental medicine resource development can be considered to be widely used These results suggest that Cnidii Rhizoma was used most with 1 don(4g) and can be widely used for the resource development to the disease such as brain, gynecology, ophthalmologhy, pediatrics and wind-associated symptoms.

• 동의생리병리학회지
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• 제22권4호
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• pp.993-999
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• 2008

Ischemic brain injury such as cerebral infarction is characterized by acute local inflammatory response mediated by cytokines. The mechanism of cytokines involved in cerebral infarction progression are uncompletely revealed yet. We investigated to find out the relationship between single nucleotide polymorphism (SNP) of interleukin 4 receptor(IL4R) and Oriental Medicine therapy efficacy in patients with cerebral infarction for 2 weeks. Oriental Korean Medicine therapies (herbal medicine and acupuncture) were applied daily and motor functions of patients were assessed using the modified cerebral vascular accident (MCVA) scores. Genotyping for IL4R polymorphism was done by pyrosequencing analysis. In IL4R genotypes and the frequency of alleles, there was no significant difference between cerebral infarction patients (n=124) and controls group (n=175). And there was also no significant difference among good and bad responders in cerebral infarction patients. In this study the IL4R genotype might not be the risk factor or a good predictive genetic marker for good and bad responders in cerebral infarction patients in Korean. Further studies including different cytokine genes will be necessary for the exact genetic markers.

• 국제물리치료학회지
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• 제2권1호
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• pp.193-200
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• 2011

This study is intended to examine the tDCS and Montoya stair task(MST) on sensorimotor recovery and glial scar expression in MCAo induced stroke model of rat. To achieve this goal, this study selected 80 SD rats of 8 weeks. The experiment groups were divided them into four groups, and assigned 20 rats to each group. Group I was a experimental control group; GroupII was a tDCS application group after MCAo; Group III was a MST application group after MCAo; Group IV was a tDCS and MST application group after MCAo. In each group, neurological function test measurement, motor behavior test, montoya stair task test, immunohistochemistric finding of GFAP expression finding were analyzed. In motor behavior test, the outcome of group I was significantly difference than the other group, especially from 14days. In montoya stair task test, the outcome of group I was significantly lower than the other group especially, group II were significantly different on 14days and group IV was most significantly difference than the other group. In immunohistochemistric finding, group II, III, IV were decrease GFAP expression on depend on time stream. These results throughout the MCAo due to focal ischemic brain injury rat model four weeks tDCS and MST was applied, when the neurobehavioural, upper extremity function and ability, histopathologic data suggest that sensorimotor function recovery and a positive influence on glial scar decrease and confirmed that.

• Clinical and Experimental Pediatrics
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• 제55권7호
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• pp.238-248
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• 2012

Purpose: Hypoxic-ischemic encephalopathy is an important cause of neonatal mortality, as this brain injury disrupts normal mitochondrial respiratory activity. Carnitine plays an essential role in mitochondrial fatty acid transport and modulates excess acyl coenzyme A levels. In this study, we investigated whether treatment of primary cultures of rat cortical neurons with L-carnitine was able to prevent neurotoxicity resulting from oxygen-glucose deprivation (OGD). Methods: Cortical neurons were prepared from Sprague-Dawley rat embryos. L-Carnitine was applied to cultures just prior to OGD and subsequent reoxygenation. The numbers of cells that stained with acridine orange (AO) and propidium iodide (PI) were counted, and lactate dehydrogenase (LDH) activity and reactive oxygen species (ROS) levels were measured. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and the terminal uridine deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay were performed to evaluate the effect of L-carnitine (1 ${\mu}M$, 10 ${\mu}M$, and 100 ${\mu}M$) on OGD-induced neurotoxicity. Results: Treatment of primary cultures of rat cortical neurons with L-carnitine significantly reduced cell necrosis and prevented apoptosis after OGD. L-Carnitine application significantly reduced the number of cells that died, as assessed by the PI/AO ratio, and also reduced ROS release in the OGD groups treated with 10 ${\mu}M$ and 100 ${\mu}M$ of L-carnitine compared with the untreated OGD group (P<0.05). The application of L-carnitine at 100 ${\mu}M$ significantly decreased cytotoxicity, LDH release, and inhibited apoptosis compared to the untreated OGD group (P<0.05). Conclusion: L-Carnitine has neuroprotective benefits against OGD in rat primary cortical neurons in vitro.

• 동의생리병리학회지
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• 제19권6호
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• pp.1666-1672
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• 2005

Oriental medicinal drugs have a broad spectrum of clinical use for the cure of nervous system diseases including brain ischemic damages or neuropathies. Yet, specific drugs or drug components used in the oriental medicine in relation to none fiber regeneration are not known. In the present study, possible growth promoting effects of oriental medicinal drugs were investigated in the injured sciatic nerve system in the rat. By immunofluorescence staining, we found that Jahageo (JHG, Hominis placenta) increased Induction levels of axonal growth associated protein GAP-43 in the rat sciatic none. Small growth promoting activity was found in Golsebo (GSB, Drynariae rhizoma) and Baikhasuo (BHSO, Polygoni multiflori radix) drugs. JHG also increased cell cycle protein Cdc2 levels in the injured area of the sciatic nerves. Immunofluorescence staining indicated that induced Cdc2 protein was mostly localized in the Schwann cells in the injury area, implying that JHG activity might be related to increased Schwann cell proliferation during axonal regeneration. Moreover, levels of phospho-extracellular signal-regulated (ERK) pathway in the injured neNes were elevated by JHG treatment while levels of total ERK were unaltered. In vivo measurement of axonal regeneration using retrograde tracer showed that JHG, GSB and BHSO significantly enhanced Dil-labeled regenerating motor neurons compared with saline control. The present data suggest that oriental medicinal drugs such as JHG, GSB, and BHSO may be a useful target for developing specific drugs of axonal regeneration.

• Journal of Ginseng Research
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• 제43권2호
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• pp.326-334
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• 2019

Background: The objective of our study was to analyze the neuroprotective effects of ginsenoside derivatives Rb1, Rb2, Rc, Rd, Rg1, and Rg3 against glutamate-mediated neurotoxicity in HT22 hippocampal mouse neuron cells. Methods: The neuroprotective effect of ginsenosides were evaluated by measuring cell viability. Protein expressions of mitogen-activated protein kinase (MAPK), Bcl2, Bax, and apoptosis-inducing factor (AIF) were determined by Western blot analysis. The occurrence of apoptotic and death cells was determined by flow cytometry. Cellular level of $Ca^{2+}$ and reactive oxygen species (ROS) levels were evaluated by image analysis using the fluorescent probes Fluor-3 and 2',7'-dichlorodihydrofluorescein diacetate, respectively. In vivo efficacy of neuroprotection was evaluated using the Mongolian gerbil of ischemic brain injury model. Result: Reduction of cell viability by glutamate (5 mM) was significantly suppressed by treatment with ginsenoside Rb2. Phosphorylation of MAPKs, Bax, and nuclear AIF was gradually increased by treatment with 5 mM of glutamate and decreased by co-treatment with Rb2. The occurrence of apoptotic cells was decreased by treatment with Rb2 ($25.7{\mu}M$). Cellular $Ca^{2+}$ and ROS levels were decreased in the presence of Rb2, and in vivo data indicated that Rb2 treatment (10 mg/kg) significantly diminished the number of degenerated neurons. Conclusion: Our results suggest that Rb2 possesses neuroprotective properties that suppress glutamate-induced neurotoxicity. The molecular mechanism of Rb2 is by suppressing the MAPKs activity and AIF translocation.