• Journal of Oriental Neuropsychiatry
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• v.22 no.4
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• pp.201-218
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• 2011

Objectives : The aim of this study was to investigate the effects of Guibi-Tang(GBT) on focal brain ischemic injury induced by intraluminal filament insertion in rats. Methods : The ischemia was induced by intraluminal filament insertion into middle cerebral artery. Sprague-Dawley rats were divided into five groups, normal group(n=8); control group was ischemia induced and no treatment(n=8); GBT 1X group was ischemia induced and administrated 42.2 mg/ml/kg of Guibi-Tang orally(n=8); GBT 3X group was ischemia induced and administrated 126.6 mg/ml/kg of Guibi-Tang orally(n=8); GBT 6X group was ischemia induced and administrated 253.2 mg/ml/kg of Guibi-Tang orally(n=8) for 21 days. mGluR5, Bax, Bcl-2 and cytochrome C were investigated to observe the effects of Guibi-Tang on apoptosis. The effects of Guibi-Tang on neuroprotective/apoptotic agents in cresyl violet, choline acetyltranferase(ChAT) with ischemic injury were investigated. Results : The intensity of mGluR5 mRNA in the hippocampal CA1 was increased in normal and GBT(Guibi-Tang) 1X groups compared with the control group. The intensity of Bax mRNA in the hippocampal CA1 was decreased in normal and GBT 1X groups compared with the control group. However it was increased unexpectedly in GBT 3X group. The intensity of Bcl-2 mRNA in the hippocampal CA1 was increased in normal and GBT 1X groups compared with the control group. The intensity of Bax/Bcl-2 ratio in the hippocampal CA1 was decreased in normal and GBT 1X groups compared with the control group. The intensity of cytochrome C protein in the hippocampal CA1 was decreased in normal, GBT 1X and GBT 6X groups compared with the control group. The density of neurons stained by cresyl violet and ChAT was increased in normal and GBT 1X groups compared with the control group. Conclusions : These results suggest that Guibi-Tang may have protective effect on vascular dementia.

• Journal of Sasang Constitutional Medicine
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• v.11 no.2
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• pp.267-281
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• 1999

1. Purpose : The purpose of this study was to determine the effects of Taeyeumjoweetang on the cerebral neurons injured by glucose oxidase(GO). 2. Methods : I observed cell viability in mouse cerebral neurons exposed to glucose oxidase by NR assay and MTT assay and determined lipid peroxidation in mouse cerebral neurons exposed to glucose oxidase. After administration of Taeyeumjoweetang water extracts, I observed significant changes of cell viability, lipid peroxidation in mouse cerebral neurons exposed to glucose oxidase. 3. Results : GO induced cell degeneration such as the decrease of cell viability was measured by MTT and NR assay in the cultured mouse cerebral cortical neurons. Taeyeumjoweetang was effective in the increase of total protein of neurons inhibited by GO. Taeyeumjoweetang was effective in the decrease of lipid peroxidation of neurons produced by GO.

• Journal of Yeungnam Medical Science
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• v.13 no.2
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• pp.159-172
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• 1996

대기오염물질이면서 동시에 생체내 화학반응의 산물이기도 한 nitric oxide(NO)는 그 생체내 분포가 광범위하고 생리적 역할이 다양하여, 최근의 생명과학 분야에서 가장 크게 주목받는 몇가지 연구대상 중 하나이다. 세포에서의 NO 산생은 nitric oxide synthase (NOS)에 의해 촉매되는데, 이들은 brain form (bNOS, neuronal; nNOS, NOS I), inducible form (iNOS), 및 endothelial form(eNOS)로 구분되는데, 이중 bNOS(nNOS)와 eNOS는 inducible form에 대비되는 constitutive form(cNOS)에 해당하므로 각각 ncNOS 와 ecNOS로도 불리운다. NOS는 아미노산인 L-arginine을 산소와 결합시켜 L-citrulline으로 변환시키면서 NO를 유리하고, 이 NO는 세포내의 guanylate cyclase를 활성화하여 cyclic GMP를 생산하거나, superoxide(O2-) 및 수소이온과 차례로 결합하여 반응성이 매우 높은 수산화기(-OH)를 발생시켜 세포독작용을 유발하기도 한다. 정상상태에서 뇌혈관내피세포의 ecNOS로 부터 유리된 NO는 혈관을 확장시켜 신경세포에 대한 산소공급을 원활히 유지해 주지만, 순환장애를 일으켰을 때는 뇌조직내의 iNOS로부터 대량의 NO가 유출되어 신경세포의 손상을 가져온다. 호흡기에서는 NO가 기도평활근을 이완시키고 폐혈류를 개선하므로, 미숙아나 성인의 호흡장애시에 소량의 NO를 흡입시키면 oxygenation을 호전시킬 수 있다. 그러나 대기오염이나 흡연 등으로 대량의 NO를 흡입할 경우 치명적인 폐부종이나 methemoglobin혈종을 일으킬 수 있다. 순환계에서는 cNOS가 혈관을 확장시켜 조직의 혈류를 유지하는데 일익을 담당한다. 세균내 독소(lipopolysaccharide; LPS)나 각종 명역조절물질들이 혈관내피세포와 혈관평활근세포로 부터 과다한 NO를 유리시키면 혈압이 급격히 떨어져 순환허탈상태에 빠지게 된다. 심장에서는 관상혈관 내피세포의 eNOS가 심근의 혈류를 유지해 주지만 허혈이나 세균내독소 또는 면역조절물질 등에 의하여 심근세포나 침윤된 대식세포의 iNOS로 부터 과량의 NO가 유리되면 심근세포의 손상이 초래된다. 신장에서는 내피세포의 cNOS에 의하여 사구체여과가 조절되고 있는데, 세균내독소나 면역 조절물질 등에 의하여 사구체관막세포(mesangial cell)등의 iNOS로 부터 과량의 NO가 유리되면 신조직과 사구체의 손상을 초래한다. 위와 같이 대부분의 장기에서 ecNOS는 조직의 혈류를 유지하는 역할을 하며, iNOS는 애초 세균 등 침입자에 대한 세포독작용이 그 존재 목적이라고 풀이할 수 있겠으나 일종의 부작용으로 자체조직의 손상을 초래하게 되는 것으로 본다. 따라서 NO와 관련된 각종 병변의 치료를 위해서는 NOS의 비선택성 억제제인 arginine 유도체 보다는 iNOS에 대한 선택적 억제제인 S-methylisothiourea(SMT), aminoethylisothiourea(AETU), aminoguanidine (AMG), agmatine, L-canavanine, transforming growth factor b1(TGF-b1) 등의 사용을 검토해 보는 것이 타당할 것으로 사료된다.

• Journal of Korean Neurosurgical Society
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• v.30 no.1
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• pp.12-19
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• 2001

Objective : Albumin is a very useful drug for the improving of cerebral blood volume and the oncotic effect in cerebral ischemia or cerebral vasospasm. The purpose of this study was to examine the morphological and neurological effect of albumin therapy on reperfusion injury following transient focal cerebral ischemia. Materials and Methods : 18 Male Sprague-Dawley rats weighing 270-320g were used. The ischemia model was produced by 2-hour period of transient middle cerebral artery occlusion with a poly-L-lysin coated intraluminal suture. The agent(20% human serum albumin[HSA]) or control solution(NaCl 0.9%) was administered intravenously at a dosage of 1% of body weight immediate after reperfusion following a 2-hour period occlusion. Neurological function was evaluated by the postural reflex and the forlimb placing test during occlusion(at 60 min) and daily for 3 days thereafter. The brain was perfusion-fixed, and infarct volumes and brain edema were measured. Results : The HSA significantly improved the neurological score in treated group. The rats of albumin treatment group showed significantly reduced total infarct volume(by 34%) and brain edema(by 81%) compared with salinetreated rats. Conclusion : HSA showed a substantial effect on the transient focal cerebral ischemia and reperfusion injury model. These results may indicate its usefulness in treating reperfusion injury patients after thrombolysis treatment for the thrombo-embolic major cerebral artery occlusions.

• Investigative Magnetic Resonance Imaging
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• v.6 no.1
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• pp.64-72
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• 2002

Purpose : To introduce and demonstrate the advantages of the new hybrid two-dimensional (2D) proton spectroscopic imaging (SI) over the single voxel spectroscopy (SVS) and conventional 2D SI in the clinical application of spectroscopy for pediatric cerebral disease. Materials and Methods : Eighty-one hybrid 2D proton spectroscopic imaging was performed in 79 children (36 normal infants and children, 10 with hypoxic-ischemic injury, 20 with toxic-metabolic encephalopathy, seven with brain tumor, three with meningoencephalitis, one with neurofibromatosis, one with Sturge-Weber syndrome and one with lissencephaly) ranging in age from the third day of life to 15 years. In adult volunteers (n=5), all three techniques including hybrid 2D proton SI, SVS using PRESS sequence, and conventional 2D proton SI were performed. Both hybrid 2D proton SI and SVS using PRESS sequence were performed in clinical cases (n=). All measurements were performed with a 1.5-T scanner using standard head quadrature coil. The 16$\times$16 phase encoding steps were set on variable field of view (FOV) depending on the size of the brain. The hybrid volume of interest inside FOV was set as $75{\times}75{\times}15{\;}\textrm{mm}^3$ or smaller to get rid of unwanted fat signal. Point-resolved spectroscopy (TR/TE=1,500 msec/135 or 270msec) was employed with standard chemical shift selective saturation (CHESSI pulses for water suppression. The acquisition time and spectral quality of hybrid 2D proton SI were compared with those of SVS and conventional 2D proton SI. Results : The hybrid 2D proton SI was successfully conducted upon all patients.

• 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.

• Journal of Chest Surgery
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• v.42 no.4
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• pp.441-446
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• 2009

Background: Side clamping of ascending aorta during proximal graft anastomosis in coronary bypassing surgery in-creases the risk of direct aortic injury as well as embolization of intimal atheroma. Heartstring proximal sealing system (Guidant Corporation, Santa Clara, Calif), developed to avoid aortic side clamping, may minimize risks of such complications. The aim of the current study is to compare the surgical outcomes of the two proximal anastomosis techniquesi.e., Heartstring system versus aortic side clamping in off pump coronary bypassing' surgery (OPCAB). Material and Method: From January 2003 to August 2008, 499 patients underwent OPCAB. Of them, proximal graft anastomosis was performed using Heartstring system in 182 patients (Group I) and conventional manual anastomosis in 317 patients (Group II). The two groups were compared for postoperative major complications and mortality. Result: Two groups showed similar characteristics in terms of preoperative demographic data, left ventricular ejection fraction, renal function and history of diabetes, hypertension and smoking. Although there was no inter-group difference in the history of cerebral ischemia (p=0.48), preoperative brain magnetic resonance angiography revealed greater incidence of severe carotid artery stenosis (>75% of lumen) in the Group I than in the. Group II (44.5% in the Group I and 30.0% in the Group II, p=0.003). There were no inter-group differences in postoperative mortality (p=0.40) and complications (p=0.47) including neurologic events (3 in the Group land 2 in the Group II, p=0.258). Whereas neurologic events all comprised transient ischemic attacks in the Group I, they comprised multiple embolic strokes in the Group II. One patient in the Group II experienced aortic dissection during proximal anastomosis which resulted in ascending aortic replacement. Conclusion: Although proximal anastomosis using Heartstring system did not show statistically significant benefit over aortic side clamping, the. absence of embolic stroke maybe a definite benefit which may be better defined through further studies over a larger cohort.

• Herbal Formula Science
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• v.14 no.1
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• pp.105-119
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• 2006

Objectives & Methods : This present study was performed to investigate the effect of Hwadamtongrak-Tang extract (HTT) on the regulation of cerebral hemodynamics in terms of regional cerebral blood flow (rCBF) and mean arterial blood pressure (MABP)] in normal and cerebral ischemic rats. Also the effects of HTT on changes in local blood flow, inhibition of LD H activity in neuronal cells, and levels of cytokine production in the serum were determined in the ischemic rat model. The major findings are summarized below. Results : 1. HTT significantly increased rCBF in a dose-dependent manner, but MABP was not changed by HTT treatment. These results suggest that HTT may increase rCBF by dilating cerebral arterial diameter. 2. HTT-induced increase in rCBF was blocked by pretreatment with cyclooxygenase inhibitor indomethacin (IDN, 1 mg/kg, i.p.) and MABP was significantly increased by ID N. 3. Pretreatment of methylene blue $(MTB,\;10\;{\mu}g/kg,\;i.p.)$, an inhibitor of guanylate cyclase, significantly decreased both rCBP and MABP in HTT-treated rats. 4. HTT treatment significantly increased rCBP to a stable level during the period of cerebral reperfusion. 5. HTT significantly inhibited LD H activity in neuronal cells, suggesting a neuroprotection by HTT. 6. Serum interleukin $(IL)-1{\beta}$ and tumor necrosis factor $(TNF)-{\alpha}$ levels were significantly decreased in the femoral artery 1 hr after middle cerebral arterial occlusion in HTT-treated rats. IL-10 levels in the serum were significantly increased by HTT treatment whereas transforming growth factor $(TGF)-{\beta}$ levels were similar between HTT-treated and control groups. 7. Serum interleukin $(IL)-1{\beta}$ and tumor necrosis factor $(TNF)-{\alpha}$ levels were significantly decreased in the femoral artery 1 hr after reperfusion in HTT-treated rats. Serum IL-10 levels were significantly decreased in HTT-treated rats compared with the control group, and no significant changes in $(TGF)-{\beta}$ in the serum were observed by HTT treatment. Conclusions: The present data suggest that HTT may have an anti-ischemic effect via the improvement of cerebral hemodynamics and thus protect the brain from ischemic damage.

• Clinical and Experimental Pediatrics
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• v.50 no.9
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• pp.882-890
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• 2007

Purpose : Preterm very low birth weight infant have high rate of adverse neurodevelopmental sequale. Recently, there have been lots of reports that human umbilical cord blood transplantation ameliorates functional deficits in animal models as hypoxic ischemic injury. This pilot study was undertaken to determine the clinical efficacy and safety of autologous umbilical cord blood cell transplantation for preventing neurodevelopmental sequale in perterm VLBW. Methods : Subjects were 26 preterm infants whose birth weight are less than 1,500 g and delivered under the intrauterine period 34 weeks. Autologous umbilical mononuclear cells (about $5.87{\times}10^7/kg$) were injected to neonate via the umbilical vein on the postnatal 24-48 hour. The therapeutic efficacy was assessed by numbers of nucleated RBC, urinary uric acid/creatinine ratio, concentration of neuron specific enolase (NSE), interleukin 6 (IL6), interleukin-$1{\beta}$ ($IL-1{\beta}$), and glial cell derived neurotrophic factor (GDNF) in serum and cerebrospinal fluid on day 1 and 7. Results : There were no significant differences in the numbers of the nucleated RBC, urinary uric acid/creatinine ratio, concentration of creatine kinase between the transplanted infants and controls. But the nucleated RBC is more likely to be rapidly discharged in the transplanted group. In the transplanted group, the concentrations of IL6, $IL-1{\beta}$, and GDNF were no significant difference between day 1 and 7, although GDNF seemed to be elevated. Serum NSE concentration was significantly elevated after transplantation, but not in CSF. Conclusion : It is suggested that autologous umbilical cord blood transplantation in preterm very low birth weight infant is safe to apply clinical practice. Long term follow up study should be needed to evaluate the potential therapeutic effect of umbilical cord blood transplantation for neuroprotection.

• Clinical and Experimental Pediatrics
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• v.48 no.12
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• pp.1330-1336
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• 2005

Purpose : It has been suggested that changes in cerebral blood flow by ventilator care could be a risk factor in periventricular leukomalacia(PVL) and severe periventricular-intraventricular hemorrhage(PV-IVH). The study aims to assess the relationship between perinatal clinical events, including ventilator care, and the development of PVL and severe PV-IVH; especially, whether ventilator care could be causers of PVL and severe PV-IVH as an individual risk factor. Methods : Among 255 very low birth weight infants who survived in the Fatima neonatal intensive care unit from January 1999 to December 2003, 15 infants with PVL and eight infants with severe PV-IVH were classified as a study group, while 231 infants were enrolled as a control group. The analysis was performed retrospectively with medical records. Results : Twenty four infants were diagnosed with PVL or severe PV-IVH. Asphyxia, recurrent apnea, sepsis, acidosis and ventilator care were significantly increased in the PVL goup. Asphyxia, recurrent apnea, RDS, acidosis and ventilator care were significantly increased in the severe PV-IVH group. Conclusion : Infants with PVL or severe PV-IVH may have multiple perinatal risk factors including asphyxia, recurrent apnea, sepsis, acidosis, RDS and ventilator care. Because most patients with ventilator care have multiple perinatal risk factors, ventilator care does not cause PVL and severe PV-IVH independently. Therefore, incidences of PVL and severe PV-IVH can be decreased by not only gentle ventilation, but also more professional antenatal care.