• The Journal of Korean Medicine
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• v.27 no.3 s.67
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• pp.107-131
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• 2006

Background and Aims: Dansamtongmek-tang (DSTMT) and Dansamsengmek-san (DSSMS) have been used for many years as therapeutic agents for the acute stage of cerebrovascular disease, hypertension and hyperlipidemia in Oriental medicine, but the effects of DSTMT and DSSMS on hyperlipidemia and safety for cell damage are not yet well-known. This study was done to investigate the effects of DSTMT and DSSMS on hyperlipidemia. Methods: In vivo test: after administering DSTMT and DSSMS to SHR and ICR occurred hyperlipidemia for 3 weeks, we analyzed body weight, cholesterol levels. TG, HDL-chol, LDL-chol, LDH in plasma, brain, liver and kidney tissue, and DNA by RT-PCR. In vitro test: after administering DSTMT and DSSMS to human hepatocellular carcinoma in hypoxia, we observed cell cohesion by light microscope, analyzed the inflow of Ca2+ by confocal laser scanning microscope and DNA by RT-PCR. Results: DSTMT significantly decreased the levels of triglyceride and increased the levels of HDL-cholesterol in SHR, and significantly decreased the levels of LDL-cholesterol and body weight and increased the levels of HDL-cholesterol in ICR. DSSMS significantly decreased body weight, total cholesterol levels, LDL-cholesterol, LDH and cardiac risk factor (CRE) in SHR and significantly decreased the levels of total cholesterol, triglyceride, LDL-cholesterol, LDH and CRF in ICR. DSTMT had an effect on protecting cells from damage by inhibiting production of p53 mRNA, and in DSSMS, by inhibiting production of p53 mRNA and p21 mRNA after hypoxia. DSTMT effectively blocked off Ca2+ at low density, but DSSMS effectively blocked off Ca2+ at high density. Both DSTMT and DSSMS had an effect on inhibiting lipid metabolism by blocking off production of apo B mRNA. Conclusions: These results suggest that DSTMT and DSSMS might be usefully applied for treatment of hyperlipidemia and suppression of brain damage.

• The Journal of Internal Korean Medicine
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• v.24 no.1
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• pp.11-20
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• 2003

Objective : Experimental studies have been done to elucidate the effect of kangwhalyupung-tang(KWYPT) on neuronal cell damage induced by brain ischemia. Method : The cytotoxic effect of ischemia was measured in the MTS assay cultures. MTS assay, INT assay, neurofilament(NF) enzymeimmuno assay(EIA). And the KWYPT on ischemia-induced neurotoxicity were examined by in vitro assays. Results : 1. The KWYPT protected effectively neuronal cell-death resulted from brain ischemia induced by the treatment of $95%N_2/5%CO_2$ for 10 min in those dependent fashion. 2. The KWYPT effectively increased the amount of NF resulting from brain ischemia, induced by the treatment of $95%N_2/5%CO_2$ for 15 min in those dependent fashions. Conclusions : KWYPT protects the brain ischemia-induced neurotoxicity through the increase of cell viability and of neurofilament in dose-dependent manner.

• The Journal of Korean Medicine
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• v.21 no.2
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• pp.68-78
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• 2000

Objective : This research was performed to investigate protective effects of Sophora subprostrata, against ischemic brain damage after a middle cerebral artery(MCA) occlusion. The effect was estimated using histological test, neurobehavioural test, and biochemical test. Methods : Rats(Sprague-Dawley) were divided into four groups: Sham operated group, MCA occluded group, Sophora subprostrata administrated group after MCA occlusion, and Normal group. The MCA was occluded by intraluminal method. Sophora subprostrata was administrated orally twice(l and 4 hours) after middle cerebral artery occlusion. The neurobeavioural test was performed at 3 hours, 6 hours, 9 hours and 24 hours after the surgery by posture reflex test and swimming behavioural test. All groups were sacrificed at 24 hours after the surgery. The brain tissue was stained with 2% triphenyl tetrazolium chioride(TTC) or 1 % cresyl violet solution, to examine effect of Sophora subprostrata on ischemic brain tissue. The blood samples were obtained from the heart of rats. Tumor necrosis factor-a level was measured from sera using Enzyme-Linked Immunoabsorbent Assay(ELISA). Results : The results showed that (1) Sophora subprostrata reduced infarct size and total infarct volume by 54.8% compared to the control group, (2) that neuronal death, which was shown by decrease in cell number and size, was attenuated significantly in the boundary area of the infarction, (3) that serum $TNF-{\alpha}$ㆍlevel was reduced significantly, and finally, there was significant recovery of motor deficit at 3 hours after MCA occluded by Swimming behavioural test. Conclusions :In conclusion, Sophora subprostrata has protective effects against ischemic brain damage at the early stage of ischemia.

• The Korea Journal of Herbology
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• v.29 no.5
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• pp.23-30
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• 2014

Objectives : Dodam-tang has been reported to have a control effect against the hyperlipidemia and thrombosis. Based upon these previous reports, this study investigates the effects of Dodam-tang on the cerebral ischemic damage of the hyperlipidemic rats. Methods : Hyperlipidemia was induced by the beef tallow 30% diet for 14 days on Sprague-Dawley rats. Ischemic damage was induced by the middle cerebral artery occlusion (MCAO) for 2 hours with the intraluminal thread method. Then water extract of Dodam-tang was administered daily for 5 days. The effect of Dodam-tang was evaluated with the serum lipids, infarct volume and edema percentage, and immunohistochemical expressions of iNOS, MMP-9, and GFAP in the brain tissue. Results : The obtained results were as follows; Dodam-tang reduced significantly the infarct size in a TTC-stained 5th brain section of the hyperlipidemic MCAO rats. Dodam-tang suppressed the infarct volume of the hyperlipidemic MCAO rats, but not significant statistically. Dodam-tang suppressed the edema percentage of the hyperlipidemic MCAO rats significantly in the brain tissue. Dodam-tang suppressed significantly the iNOS expression in the cerebral penumbra and caudate putamen of the hyperlipidemic MCAO rats. Dodam-tang suppressed significantly the MMP-9 expression in the cerebral penumbra of the hyperlipidemic MCAO rats. Dodam-tang suppressed significantly the GFAP-expressed atrocytes in the cerebral penumbra of the hyperlipidemic MCAO rats. Conclusions : These results suggest that Dodam-tang suppresses the brain edema formation through the suppression of the iNOS, MMP-9 and GFAP, but the neuroprotective effect against the cerebral infarct are not distinct.

• Korean Journal of Veterinary Service
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• v.47 no.2
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• pp.101-105
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• 2024

Three dogs (7-year-old, neutered male Chihuahua; case 1, 1-year-old, spayed female mixed breed; case 2, 10-month-old, female Maltese; case 3) were referred to Jeju Veterinary Medicine Teaching Hospital for traumatic brain injury. All three patients exhibited abnormal neurological symptoms. The patients were diagnosed through medical history obtained from their caregivers and through computed tomography (CT) or magnetic resonance imaging (MRI) scans. Structural brain abnormalities were observed in two dogs through CT scans and in one dog through MRI. Decompression therapy with mannitol was administered to all three dogs. Case 1, which showed CT findings of pulmonary hemorrhage but no significant brain injury, and case 2, which had mild brain damage on CT imaging, showed improvement in neurological symptoms and gait abnormalities after decompression therapy. However, case 3, which showed suspected brain hemorrhage and brain edema on MRI, did not respond to decompression therapy and was euthanized one month later. Imaging evaluation through CT or MRI in dogs with traumatic brain injury can assist clinical veterinarians in assessing the prognosis of patients.

• Journal of Ginseng Research
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• v.44 no.4
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• pp.593-602
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• 2020

Background: Heat stress orchestrates neurodegenerative disorders and results in the formation of reactive oxygen species that leads to cell death. Although the immunomodulatory effects of ginseng are well studied, the mechanism by which ginseng alleviates heat stress in the brain remains elusive. Methods: Rats were exposed to intermittent heat stress for 6 months, and brain samples were examined to elucidate survival and antiinflammatory effect after Korean Red Ginseng (KRG) treatment. Results: Intermittent long-term heat stress (ILTHS) upregulated the expression of cyclooxygenase 2 and inducible nitric oxide synthase, increasing infiltration of inflammatory cells (hematoxylin and eosin staining) and the level of proinflammatory cytokines [tumor necrosis factor α, interferon gamma (IFN-γ), interleukin (IL)-1β, IL-6], leading to cell death (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay) and elevated markers of oxidative stress damage (myeloperoxidase and malondialdehyde), resulting in the downregulation of antiapoptotic markers (Bcl-2 and Bcl-x_L) and expression of estrogen receptor beta and brain-derived neurotrophic factor, key factors in regulating neuronal cell survival. In contrast, KRG mitigated ILTHS-induced release of proinflammatory mediators, upregulated the mRNA level of the antiinflammatory cytokine IL-10, and increased myeloperoxidase and malondialdehyde levels. In addition, KRG significantly decreased the expression of the proapoptotic marker (Bax), did not affect caspase-3 expression, but increased the expression of antiapoptotic markers (Bcl-2 and Bcl-x_L). Furthermore, KRG significantly activated the expression of both estrogen receptor beta and brain-derived neurotrophic factor. Conclusion: ILTHS induced oxidative stress responses and inflammatory molecules, which can lead to impaired neurogenesis and ultimately neuronal death, whereas, KRG, being the antioxidant, inhibited neuronal damage and increased cell viability.

• Journal of Acupuncture Research
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• v.21 no.4
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• pp.207-215
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• 2004

Objective : In order to prove the effect of Hirudin Herbal-acupuncture this experimental studies were performed by using rats that had neuronal damage due to the Middle Cerebral Artery Occulsion(MCAO). Methods : Microdialysis probes were implanted into the coordinate of striatum of anesthetized rats which consist of sham-operated 8 rats, MCAO-operated 8 rats and Hirudin Herbal-acupuncture administrated 8 rats before MCAO operating. The Hirudin Herbal-acupuncture(0.5mg/kg) was administrated to rats 30 minutes before having an operation causing the MCAO. The surgical excision lead the cross resected brain to the acute ischemic state. The brain was sliced in 2mm thickness and stained with cresyl violet buffer for the measurement of cerebral infarcted area and volume. Results : Based on the result of the tissue inspection for the cerebral ischemic cell, Hirudin Herbal-acupuncture significantly protect neurocytes. Conclusion : We suggest Hirudin Herbal-acupuncture produces protective effects against the neuronal damage induced by MCAO. Therefore, Hirudin Herbal-acupuncture may prevent delayed neuronal death(DND) in selectively vulnerable focal areas of the brain effectively.

• Korean Journal of Acupuncture
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• v.21 no.3
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• pp.89-96
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• 2004

Objectives : In order to prove the effect of Phospholipase $A_2(PLA_2)$ Herbal-acupuncture, this experimental studies were performed by using rats that had neuronal damage due to the Middle Cerebral Artery Occulsion(MCAO). Methods : Microdialysis probes were implanted into the coordinate of striatum of anesthetized rats which consist of sham-operated 8 rats, MCAO-operated 8 rats and $PLA_2$ Herbal-acupuncture administrated 8 rats before MCAO operating. The $PLA_2$ Herbal-acupuncture(0.5mg/kg) was administrated to rats 30 minutes before having an operation causing the MCAO. The surgical excision lead the cross resected brain to the acute ischemic state. The brain was sliced in 2mm thickness and stained with cresyl violet buffer for the measurement of cerebral infarcted area and volume. Results : Based on the result of the tissue inspection for the cerebral ischemic cell, $PLA_2$ Herbal-acupuncture significantly protect neurocytes. Conclusions : We suggest $PLA_2$ Herbal-acupuncture produces protective effects against the neuronal damage induced by MCAO. Therefore, $PLA_2$ Herbal-acupuncture may prevent delayed neuronal death(DND) in selectively vulnerable focal areas of the brain effectively.

• Journal of Ginseng Research
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• v.44 no.1
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• pp.79-85
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• 2020

Background: Helicobacter pylori increases reactive oxygen species (ROS) and induces oxidative DNA damage and apoptosis in gastric epithelial cells. DNA damage activates DNA damage response (DDR) which includes ataxia-telangiectasia-mutated (ATM) activation. ATM increases alternative reading frame (ARF) but decreases mouse double minute 2 (Mdm2). Because p53 interacts with Mdm2, H. pylori-induced loss of Mdm2 stabilizes p53 and induces apoptosis. Previous study showed that Korean Red Ginseng extract (KRG) reduces ROS and prevents cell death in H. pylori-infected gastric epithelial cells. Methods: We determined whether KRG inhibits apoptosis by suppressing DDRs and apoptotic indices in H. pylori-infected gastric epithelial AGS cells. The infected cells were treated with or without KRG or an ATM kinase inhibitor KU-55933. ROS levels, apoptotic indices (cell death, DNA fragmentation, Bax/Bcl-2 ratio, caspase-3 activity) and DDRs (activation and levels of ATM, checkpoint kinase 2, Mdm2, ARF, and p53) were determined. Results: H. pylori induced apoptosis by increasing apoptotic indices and ROS levels. H. pylori activated DDRs (increased p-ATM, p-checkpoint kinase 2, ARF, p-p53, and p53, but decreased Mdm2) in gastric epithelial cells. KRG reduced ROS and inhibited increase in apoptotic indices and DDRs in H. pylori-infected gastric epithelial cells. KU-55933 suppressed DDRs and apoptosis in H. pylori-infected gastric epithelial cells, similar to KRG. Conclusion: KRG suppressed ATM-mediated DDRs and apoptosis by reducing ROS in H. pylori-infected gastric epithelial cells. Supplementation with KRG may prevent the oxidative stress-mediated gastric impairment associated with H. pylori infection.

• Biomolecules & Therapeutics
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• v.20 no.4
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• pp.357-370
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• 2012

Radiation therapy, the most commonly used for the treatment of brain tumors, has been shown to be of major significance in tumor control and survival rate of brain tumor patients. About 200,000 patients with brain tumor are treated with either partial large field or whole brain radiation every year in the United States. The use of radiation therapy for treatment of brain tumors, however, may lead to devastating functional deficits in brain several months to years after treatment. In particular, whole brain radiation therapy results in a significant reduction in learning and memory in brain tumor patients as long-term consequences of treatment. Although a number of in vitro and in vivo studies have demonstrated the pathogenesis of radiation-mediated brain injury, the cellular and molecular mechanisms by which radiation induces damage to normal tissue in brain remain largely unknown. Therefore, this review focuses on the pathophysiological mechanisms of whole brain radiation-induced cognitive impairment and the identification of novel therapeutic targets. Specifically, we review the current knowledge about the effects of whole brain radiation on pro-oxidative and pro-inflammatory pathways, matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs) system and extracellular matrix (ECM), and physiological angiogenesis in brain. These studies may provide a foundation for defining a new cellular and molecular basis related to the etiology of cognitive impairment that occurs among patients in response to whole brain radiation therapy. It may also lead to new opportunities for therapeutic interventions for brain tumor patients who are undergoing whole brain radiation therapy.