• 대한의생명과학회지
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• 제11권2호
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• pp.201-209
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• 2005

This study aimed to investigate the cerebroprotective effect of nociceptin on transient focal cerebral ischemia in Sprague-Dawley rats by determining the changes in regional cerebral blood flow (rCBF) and the infarct size. Right middle cerebral artery (MCA) was occluded for 2 hours, and thereafter was followed by reperfusion by an intraluminal monofilament technique. An open cranial window was made on the right parietal bone for determination of continuous changes in rCBF by laser-Doppler flowmetry. The infarct size was morphometrically determined using the 2,3,5-triphenyltetrazolium chloride technique. In normal rats, nociceptin ($0.01\~100\;nmol/kg$, Lv.) increased rCBF and decreased cerebral arterial resistance in a dose-dependent manner. Systemic arterial blood pressure was little affected by nociceptin at the doses of 0.01 and 0.1nmol/kg, but dose-dependently reduced at the doses of 1 nmol/kg or more. In transient cerebral ischemic rats, nociceptin ($0.01\~0.1$ nmol/kg, i.p.) significantly attenuated the postischemic cerebral hyperemia, and progressively increased rCBF. The improving effect of nociceptin on the postischemic rCBF response was markedly blocked by pretreatment with $[Nphe^1]nociceptin(1-13)NH_2$ (1 nmol/kg, i.p.), a selective nociceptin receptor antagonist, but not by naloxone ($3{\mu}mol/kg$, i.p.), a selective opioid receptor antagonist. The cerebral infarct size was significantly reduced by nociceptin ($0.01\~0.1$ nmol/kg) administered i.p. 5 min after MCA occlusion in transient cerebral ischemia of 2-hour MCA occlusion and 22-hour reperfusiion. It is suggested that nociceptin improves the postischemic cerebral hemodynamics and thereby has a cerebroprotective effect in transient focal cerebral ischemia.

• 동국한의학연구소논문집
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• 제11권
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• pp.58-65
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• 2008

Objectives : BHT has been commonly used to treatment of brain disorders in Oriental clinic in Korea. The purpose of this study was to determine the inhibitory effect of modified BHT-C extract on the transient forcal cerebral ischemia in rats. Method : We prepared ischemic rats by the transient middle cerebral artery occlution(MCAO; 90 min occlusion and 144 h reperfusion) in rat brains. BHT-C extract (100 and 200 mg/kg, i.p.) was administered every day after the onset of MCAO until 6 day. Result : BHT-C extract increased survival rate of ischemic rats compared with vehicle-treated rats. BHT-C extract treated rats (100 and 200 mg/kg) were shown a significant reduction in infarct volume compared with vehicle-treated rats. Conclusions : These results suggest that BHT-C extract may contribute to its protective effects in brain ischemia through the reduction of brain infarction.

• Preventive Nutrition and Food Science
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• 제16권3호
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• pp.217-223
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• 2011

Ischemic stroke constitutes about 80% of all stroke incidences. It is characterized by brain cell death in a region where cerebral arteries supplying blood are occluded. Under these ischemic conditions, apoptosis is responsible for the cell death, at least in part. Goat's-beard (Aruncus dioicus var. kamtschaticus) is a perennial plant that grows naturally in the alpine regions of Korea. In the present study, we first determined whether water extract of goat's-beard (HY1646) and some of its fractions prepared by partitioning with organic solvents could improve the viability of human hepatocellular carcinoma cells (HepG2) cultured under hypoxic condition by blocking apoptotic pathways. Based on the in vitro findings, we subsequently investigated whether HY1646 and the ethyl acetate fraction (EA) selected from cell culture-based screening could attenuate brain injury in a rat middle cerebral artery occlusion (MCAO) model of ischemia (2 hr), followed by 22 hours of reperfusion. The cell number was sustained close to that initially plated in the presence of HY1646 even after 24 hr of cell culture under hypoxic condition (3% $O_2$), at which time the cell number reached almost zero in the absence of HY1646. This improvement in cell viability was attributed to the delay in apoptosis, identified by the formation of DNA ladder in gel electrophoresis. Of fractions soluble in hexane, ethyl acetate (EA) and butanol, EA was chosen for the animal experiments because EA demonstrated the best cell viability at the lowest concentration (10 ${\mu}g$/mL). HY1646 (200 mg/kg) and EA (10 and 20 mg/kg) significantly reduced infarct size, an index of brain injury, by 16.6, 40.0 and 61.0%, respectively, as assessed by 2,3,5-triphenyl tetrazolium chloride staining. The findings suggest that prophylactic intake of goat's beard might be beneficial for preventing ischemic stroke.

• 동의생리병리학회지
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• 제18권2호
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• pp.419-426
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• 2004

This experimental study was designed to investigate the effects of Yukgunja-tang(YGJT) on the inhibition of cerebral ischemia in rats. And We measured regional cerebral blood f1ow(rCBF) and pial arterial diameter(PAD) in cerebral ischemic rats, and cytokines production in serum Of cerebral ischemic rats. The results were as follows; Both rCBF and PAD were significantly and stably increased by YGJT(10 mg/kg, i.p.) during the period of cerebral reperfusion, which contrasted with the findings of rapid and marked increase in control group. In cytokine production of serum by drawing from femoral arterial blood after middle cerebral arterial occlusion(MCAO) 1 hr, IL-1β and TGF-β production of sample group were similar to that of control group, but sample group was decreased TNF-α production compared with control group, and was significantly increased IL-10 production in compared with control group. In cytokine production of serum by drawing from femoral arterial blood after reperfusion 1 hr, sample group was significantly decreased IL-1β and TNF-α production compared with control group, but TGF-β production of sample group was similar to that of control group, and sample group was significantly increased IL-10 production compared with control group. In cytokine production of serum by drawing from femoral arterial blood after reperfusion 4 hrs, sample group was significantly decreased IL-1β production compared with control group, and sample group was decreased TNF-α production in compared with control group, but TGF-β production of sample group was similar to that of control group, and sample group was increased IL-10 production compared with control group. This results were suggested that YGJT has inhibitive effect on the brain damage by inhibited IL-1β production and TNF-α production, but accelerated IL-10 production. We thought that YGJT should have an anti-ischemic effect through the improvement of cerebral hemodynamics and inhibitive effect on the brain damage.

• Journal of Ginseng Research
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• 제40권2호
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• pp.196-202
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• 2016

Background: Ginsenoside Rd (GSRd), a main component of the root of Panax ginseng, exhibits anti-inflammation functions and decreases infarct size in many injuries and ischemia diseases such as focal cerebral ischemia. M1 Macrophages are regarded as one of the key inflammatory cells having functions for disease progression. Methods: To investigate the effect of GSRd on renal ischemia/reperfusion injury (IRI) and macrophage functional status, and their regulatory role on mouse polarized macrophages in vitro, GSRd (10-100 mg/kg) and vehicle were applied to mice 30 min before renal IRI modeling. Renal functions were reflected by blood serum creatinine and blood urea nitrogen level and histopathological examination. M1 polarized macrophages infiltration was identified by flow cytometry analysis and immunofluorescence staining with $CD11b^+$, $iNOS^+$/interleukin-12/tumor necrosis factor-${\alpha}$ labeling. For the in vitro study, GSRd ($10-100{\mu}g/mL$) and vehicle were added in the culture medium of M1 macrophages to assess their regulatory function on polarization phenotype. Results: In vivo data showed a protective role of GSRd at 50 mg/kg on Day 3. Serum level of serum creatinine and blood urea nitrogen significantly dropped compared with other groups. Reduced renal tissue damage and M1 macrophage infiltration showed on hematoxylin-eosin staining and flow cytometry and immunofluorescence staining confirmed this improvement. With GSRd administration, in vitro cultured M1 macrophages secreted less inflammatory cytokines such as interleukin-12 and tumor necrosis factor-${\alpha}$. Furthermore, macrophage polarization-related pancake-like morphology gradually changed along with increasing concentration of GSRd in the medium. Conclusion: These findings demonstrate that GSRd possess a protective function against renal ischemia/reperfusion injury via downregulating M1 macrophage polarization.

• 동의신경정신과학회지
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• 제18권1호
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• pp.185-196
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• 2007

Objective : This experimental Study was designed to investigate the effects of FOENICULI FRUCTUS(FF) on the change of inhibition lactate dehydrogenase(LDH) activity in neuronal cells and cytokines production in serum of cerebral ischemic rats. Method : FOENICULI FRUCTUS(FF)freeze dry powder and FF on the LDH activity in neuronal cells. Changes of FF on the physiological parameters(PaO2, PaCO2, MABP and HR) in crerbral ischemic rats. Effects of FF on the IL-1beta production, $TNF-{\alpha}$ production, $TGF-{\beta}$ production, and IL-10 in serum of cerebral ischemic rats. MCAO :. cytokines production of serum by drawing from femoral arterial blood after MCAO 1 hr. Reperfusion : cytokines production of serum by drawing from femoral arterial blood after reperfusion 1 hr. Results and Conclusion : 1. FF did not inhibit lactate dehydrogenase(LDH) activity in neuronal cells. 2. In serum by drawing from femoral arterial blood after middle cerebral arterial occlusion(MCAO) 1 hr and reperfusion 1 hr, sample group was significantly decreased $IL-l{\beta}$ production compared with control group 3. In serum by drawing from femoral arterial blood after MCAO 1 hr and reperfusion 1 hr, sample group was significantly decreased $TNF-{\alpha}$ production compared with control group. 4. In serum by drawing from femoral arterial blood after MCAO 1 hr and reperfusion 1 hr, sample group was significantly increased $TGF-{\beta}$ production compared with control group. 5. In serum by drawing from femoral arterial blood after reperfusion 1 hr, sample group was significantly increased IL-10 production compared with control group. This results were suggested that FF had inhibitive effect on the brain damage by inhibited LDH activity, $IL-l{\beta}$ and $TNF-{\alpha}$production, but accelerated $TGF-{\beta}$ production and IL-10 production.

• 동의생리병리학회지
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• 제17권1호
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• pp.64-70
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• 2003

Jaeumgenby-tang(JGT) have been used in oriental medicine for many centuries as a therapeutic agent of vertigo caused by deficiency of qi(氣) and blood(血). Effect of Aurantii Fructus(AF) take off the phlegm by promoting the circulation of qi, Gastrodae Rhizoma(GR) has effects treating for headache, vertigo by calming the liver and suppressing hyperactivity of the liver-yang(陽). And, I designed to investigate whether injection of JGT adding AFㆍGR extract(JGTAG) affects cytotoxicity in vitro, cerebral hemodynamics [regional cerebral blood flow(rCBF), pial arterial diameter(PAD), mean arterial blood pressure(MABP)] in normal and cerebral ischemia rats by MCA occlusion method. The changes of rCBF and MABP were determinated by laser-doppler flowmetry(LDF), and the change of PAD was determinated by video microscope and width analyzer. The results were as follows in normal rats; JGTAG was not cytotoxicity in brain cells. And JGTAG was significantly increased rCBF, PAD and MABP. This results suggest that JGTAG increased significantly rCBF by dilating PAD. And the results were as follows in cerebral ischemic rats; The changes of rCBF and PAD were increased stably by treatment with JGTAG(10mg/kg, i.v.) during the period of cerebral reperfusion, and pretreatment with propranolol and indomethacin were increased JGT AG induced increase of rCBF and PAD during the period of cerebral reperfusion. We suggest that JGTAG has an anti-ischemic effect through the improvement of cerebral hemodynamics.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1995년도 춘계학술대회
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• pp.38-40
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• 1995

There have reports suggested that cerebral blood flow (CBF) has decreased in patients with both senile dementia of the Alzheimer's type and multi-infarct dementia, which are characterized by marked cognitive impairments. In addition, recent studies have demonstrated that decrease of CBF precedes the onset of multi-infarct dementia. These findings further suggest that chronic reduction of CBF may play an important role in the formation and progression of cerebral vascular dementia. Although transient cerebral ischemia, based upon vascular “reperfusion”, is apparently not paralleling the clinical condition, the transient cerebral ischemia model is one of the major methods investigated and the other is the cerebral embolism operation. Cognitive impairment and neuronal damages have been fully studied using these transient and/or embolic ischemia models. There are, however, few investigations focused the attention on the influence of chronic decrease of CBF on cognitive processes. In the present study, we have chosen a chronic ischemic model which is produced by permanent occlusion of bilateral common carotid arteries (2VO) in rats to investigate the neuronal damage and cognitive deficits through radial maze performance. We investigated furtherly the effects of tetramethylpyrazine (TMP), a constituent isolated from Ligusticum Chuanxiong on such a model.

• Journal of Korean Neurosurgical Society
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• 제46권1호
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• pp.31-37
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• 2009

Objective : This study was performed to elucidate the technical and patient-specific risk factors for postoperative ischemia in patients undergoing temporary arterial occlusion (TAO) during the surgical repair of their aneurysms. Methods : Eighty-nine consecutive patients in whom TAO was performed during surgical repair of an aneurysm were retrospectively analyzed. The demographics of the patients were analyzed with respect to age. Hunt and Hess grade on admission, Fisher grade of hemorrhage, aneurysm characteristics, timing of surgery, duration of temporary occlusion, and number of temporary occlusive episodes. Outcome was analyzed at the 3-month follow-up, along with the occurrence of symptomatic and radiological stroke. Results : In overall, twenty-seven patients (29.3%) had radiologic ischemia attributable to TAO and fifteen patients (16.3%) had symptomatic ischemia attributable to TAO. Older age and poor clinical grade were associated with poor clinical outcome. There was a significantly higher rate of symptomatic ischemia in patients who underwent early surgery (p=0.007). The incidence of ischemia was significantly higher in patients with TAO longer than 10 minutes (p=0.01). In addition, patients who underwent repeated TAO, which allowed reperfusion, had a lower incidence of ischemia than those who underwent single TAO lasting for more than 10 minutes (p=0.011). Conclusion : Duration of occlusion is the only variable that needs to be considered when assessing the risk of postoperative ischemic complication in patients who undergo temporary vascular occlusion. Attention must be paid to the patient's age, grade of hemorrhage, and the timing of surgery. In addition, patients undergoing dissection when brief periods of temporary occlusion are performed may benefit more from intermittent reperfusion than continuous clip application. With careful planning, the use of TAO is a safe technique when used for periods of less than 10 minutes.

• Journal of Magnetics
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• 제19권4호
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• pp.357-364
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• 2014

This study examined effect of a transcranial magnetic stimulation device with a commercial-frequency approach on the neuronal cell death caused ischemia. For a simple transcranial magnetic stimulation device, the experiment was conducted on an ischemia induced rat by transcranial magnetic stimulation of a commercial-frequency approach, controlling the firing angle using a Triac power device. The transcranial magnetic stimulation device was controlled at a voltage of 220 V 60 Hz and the trigger of the Triac gate was varied from $45^{\circ}$ up to $135^{\circ}$. Cerebral ischemia was caused by ligating the common carotid artery of male SD rats and reperfusion was performed again to blood after 5 minutes. Protein Expression was examined by Western blotting and the immune response cells reacting to the antibodies of Poly ADP ribose polymerase in the cerebral nerve cells. As a result, for the immune response cells of Poly ADP ribose polymerase related to necrosis, the transcranial magnetic stimulation device suppressed necrosis and had a protective effect on nerve cells. The effect was greatest within 12 hours after ischemia. Therefore, it is believed that in the case of brain damage caused by ischemia, the function of brain cells can be restored and the impairment can be improved by the application of transcranial magnetic stimulation.