• 동의생리병리학회지
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• 제27권2호
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• pp.173-182
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• 2013

This Study was designed to investigate the effects of Sibjeondaebo-tang (SDT) and Gamy-Sibjeondaebo-tang (GST, Sibjeondaebo-tang adding Cervi Pantotrichum Cornu) on the improvement in 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. And, It was to investigate the effects of the SDT and GST with the change of histologic examination through the BDNF in the hippocampus CA1. In changes of cerebral hemodynamics, SDT and GST significantly increased rCBF in a dose-dependent manner but decreased MABP in normal rats. In mechanism of cerebral hemodynamics, Increase of GST-induced rCBF was significantly inhibited by pretreatment with methylene blue (0.01 mg/kg, i.p.), an inhibitor of guanylate cyclase, and Decrease of GST-induced MABP was significantly increased by pretreatment with methylene. These results suggested that the action of GST was mediated by guantlate cyclase pathway. In cerebral ischemics, the rCBF was stably improved by SDT (10 mg/kg, i.p.) significantly and stably increased by GST (10 mg/kg, i.p.) during the period of cerebral reperfusion, which contrast with the findings of rapid and marked increase in Control group. These results suggested that GST had anti-ischemic action in cerebral ischemic state. In histological examination through TTC stain, Sample A group and Sample B group decreased discoloration in the cortical part at $28^{th}$ day after MCAO induction. In immunohistochemistric response of BDNF, Sample A group and Sample B group increased respondent effect at $28^{th}$ day after MCAO induction. These results suggest that GST can Increase rCBF in normal state, as well as improve the stability of rCBF in cerebral ischemic state. Furthermore, methylene blue inhibitor study suggested the mechanism of blood flow enhancement by GST may be mediated by guanylate cyclase pathway.

• Journal of Korean Neurosurgical Society
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• 제51권2호
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• pp.75-80
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• 2012

Objective : To optimize the recanalization of acute cerebral stroke that were not effectively resolved by conventional intraarterial thrombolysis (IAT), we designed a double device technique to allow for rapid and effective reopening. In this article, we describe the feasibility and efficacy of this technique. Methods : From January 2008 to September 2009, twenty patients with acute cerebral arterial occlusion (middle cerebral artery : n=12; internal carotid artery terminus : n=5; basilar artery : n=3) were treated by the double device technique. This technique was applied when conventional thrombolytic methods using drug, microwires, microcatheters and balloons did not result in recanalization. In the double device technique, two devices are simultaneously placed at the lesion (for example, one microcatheter and one balloon or two microcatheters). Chemicomechanical or mechanicomechanical thrombolysis was performed simultaneously using various combinations of two devices. Recanalization rates, procedural time, complications, and clinical outcomes were analyzed. Results : The initial median National Institute of Health Stroke Scale (NIHSS) was 16 (range 5-26). The double device technique was applied after conventional IAT methods failed. Recanalization was achieved in 18 patients (90%). Among them, 55% (11 cases) were complete (thrombolysis in cerebral infarction 2B, 3). The median thrombolytic procedural time including the conventional technique was $135{\pm}83.7$ minutes (range 75-427). Major symptomatic hemorrhages (neurological deterioration ${\geq}4$ points in NIHSS) developed in two patients (10%). Good long term outcomes (modified Rankin Scale ${\leq}2$ at 90 days) occurred in 25% (n=5) of the cases. Mortality within 90 days developed in two cases (10%). Conclusion : The double device technique is a feasible and effective technical option for large vessel occlusion refractory to conventional thrombolysis.

• 동의생리병리학회지
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• 제17권5호
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• pp.1194-1201
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• 2003

Jaeumgenby-tang(JGT) have been used in oriental medicine for many centries 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 headarch, vertigo by calming the liver and suppressing hyperactivity of the liver-yang (陽). I investigated whether injection of JGT adding AFㆍGR extract(JTG) affects cerebral hemodynamics [regional cerebral blood f1ow(rCBF), pial arterial diameter(PAD) in cerebral ischemia rats by MCA occlusion method, and I designed to make manifest whether JTG is mediated by adrenergic β-receptor, cyclooxygenase or guanylate cyclase. The changes of rCBF was determinated by laser-doppler flowmetry(LDF), and the changes of PAD was determinated by video microscope and width analyzer. The results were as follows in cerebral ischemic rats; The changes of rCBF and PAD were increased stabilizly by treatment with JTG(10 ㎎/kg, i.v.) during the period of cerebral reperfusion, and pretreatment with propranolol and indomethacin were increased JTG induced increase of rCBF and PAD during the period of cerebral reperfusion. Pretreatment methylene blue was decreased JTG induced increase of rCBF and PAD during the period of cerebral reperfusion. In conclusion, JTG causes a diverse response of rCBF and PAD, and action of JTG is mediated by adrenergic β-receptor and cyclooxygenase. I suggest that JTG has an anti-ischemic effect through the improvement of crebral hemodynamics.

• 동의생리병리학회지
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• 제18권6호
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• pp.1643-1651
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• 2004

This experimental study was designed to investigate the effects of SIEGESBECKIAE HERBA extract (SHE) on the change of cerebral hemodynamics 〔regional cerebral blood flow (rCBF) and mean arterial blood pressure(MABP)〕 in normal condition and cerebral ischemic rats, and to determine the mechanism of action of SHE. This study was designed to investigate whether or not SHE inhibit lactate dehydrogenase (LDH) activity in neuronal cells and cytokines production in serum of cerebral ischemic rats. The results were as follows SHE increased rCBF significantly in a dose-dependent manner, but MABP was not changed by SHE in normal rats. The SHE-induced increase in rCBF was significantly inhibited by pretreatment with indomethacin (IDN), an inhibitor of cyclooxygenase but was increased by methylene blue (MTB), an inhibitor of guanylate cyclase. SHE inhibited lactate dehydrogenase (LDH) activity significantly in neuronal cells. rCBF was increased significantly and stably by SHE(10㎎/㎏, i.p.) during the period of cerebral reperfusion, which contrasted with the findings of rapid and marked increase in control group in ischemic rats. In serum by drawing from femoral arterial blood after middle cerebral arterial occlusion(MCAO) for 1hr and reperfusion for 1hr, the sample group was decreased IL-1β production significantly compared to that of the control group. In serum by drawing from femoral arterial blood after MCAO 1hr and reperfusion 1hr, sample group decreased TNF-α production significantly compared to that of the control grolilp. In serum by drawing from femoral arterial blood after reperfusion 1hr, sample group increased TGF-β production significantly compared to that of the control group. In serum by drawing from femoral arterial blood after MCAO for 1hr and reperfusion for 1hr, IL-10 production of the sample group was similar to that of control group. These results suggested that SHE had inhibitive effect on the brain damage by inhibited LDH activity, IL-1β and TNF-α production, but accelerated TGF-β production.

• 동의생리병리학회지
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• 제26권5호
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• pp.657-664
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• 2012

The aim of this study is to investigate the effects of onion vinegar on the cerebral blood flow by measuring the changes of regional cerebral blood flow (rCBF) and mean arterial blood pressure (MABP) and by observing the recovery of focal ischemic brain injury in rats. Rats are divided into thee groups depending on the medication; control group (no medication), 8.8-OV group (vinegar using 8.8 brix onion medication), 14.6-OV group (vinegar using 14.6 brix onion medication). The medication of onion vinegar significantly increased rCBF but decreased MABP. This result suggests that onion vinegar significantly increased rCBF by dilating arterial diameter. In addition, focal ischemic brain injury is induced in rats by middle cerebral arterial occlusion. The recovery from focal ischemic brain injury is more significantly improved in the groups using onion vinegar compared to the control group. The amount of recovery is measured by the GAP-43 and the medication of onion vinegar significantly increased GAP-43. This result suggests that onion vinegar is effective on the nerve regeneration. After the medication, the change of body weight, outcomes of renal and liver function test, and outcomes of CBC are analysed for safety examination. There are no statistical differences among control group and all experimental groups in the body weight, renal and liver function test, and CBC. In conclusion, these results suggest that onion vinegar can increase rCBF in normal state, and improve the stability of rCBF in ischemic state.

• 동의생리병리학회지
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• 제18권6호
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• pp.1714-1721
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• 2004

This experimental study was designed to investigate the mechanism of Palmul-Tang(PMT) on the changes of cerebral hemodynamics in rats. The changes of cerebral hemodynamics in normal rats were as follows ; The PMT-induced increase in regional cerebral blood flow was significantly inhibited by pretreatment with indomethacin(1㎎/㎏, i.p.), an inhibitor of cyclooxygenase, and was inhibited by methylene blue(10㎍/㎏, i.p.), an inhibitor of guanylate cyclase. The PMT-induced dilation in pial arterial diameter was significantly inhibited by pretreatment with indomethacin and methylene blue. The PMT-induced increase in mean arterial blood pressure was significantly inhibited by pretreatment with indomethacin but was increased by methylene blue. This results were suggested that the mechanism of PMT was mediated by cyclooxygenase. The changes of cytokine production in cerebral ischemic rats were as follows ; In cytokine production of serum by drawing from femoral arterial blood after middle cerebral arterial occlusion 1hr, sample group was decreased IL-1β and TNF-α production compared with control group, IL-10 production of sample group was similar to that of control group, but sample group was significantly increased TGF-β production compared with control group. In cytokine production of serum by drawing from femoral arterial blood after reperfusion 1hr, sample group was significantly decreased IL-1β production compared with control group and decreased TNF-α production compared with control group. IL-10 production of sample group was similar to that of control group, but sample group was significantly increased TGF-β 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, but IL-10 production of sample group was similar to that of control group. sample group was increased TNF-α and TGF-β production compared with control group. These results suggested that PMT had inhibitive effect on the brain damage by inhibiting IL-1β and TNF-α production, but by accelerating TGF-β production. The present author thought that PMT had an anti-ischemic effect through the improvement of cerebral hemodynamics and inhibitive effect on the brain damage.

• 동의생리병리학회지
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• 제27권4호
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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.

• 동의생리병리학회지
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• 제21권5호
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• pp.1127-1134
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• 2007

The study was designed to investigate the mechanism of Patholoobi Caulis freeze dried powder (PCF) on the regional cerebral blood flow (rCBF) and mean arterial blood pressure (MABP) in normal rats and cytokines production ($IL-1{\beta}$, $TNF-{\alpha}$, IL-10, $TGF-{\beta}$) in cerebral ischemic rats. The results in normal rats were as follows ; Increase of PCF-induced rCBF was significantly inhibited by pretreatment with methylene blue (10 ${\mu}g/kg$, I.p.), an inhibitor of guanylate cyclase, and was inhibited by indomethacin (1 mg/kg, i.p.), an inhibitor of cyclooxygenase. Increase of PCF-induced MABP was decreased by pretreatment with methylene blue, but was increased by indomethacin. These results suggested that the mechanism of action PCF was mediated by cyclic 3',5'-guanosine monophosphate. The results in cerebral ischemic rats were as follows ; In cytokine production in serum from femoral arterial blood 1 hr after middle cerebral arterial occlusion, PCF (10 mg/kg. i.p.) significantly decreased $IL-1{\beta}$ and $TNF-{\alpha}$ production, and increased IL-10 production compared with control group. In cytokine production in serum from femoral arterial blood 1 hr 1 hr after reperfusion, PCF (10 mg/kg, i.p.) significantly decreased $IL-1{\beta}$ production, and incresed IL-10 production compared with control group. These results suggested that PCF was significantly and stably increased regional cerebral blood flow by inhibiting $IL-1{\beta}$ production, and by accelerating IL-10 production.

• 대한한의학방제학회지
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• 제14권1호
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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.

• Journal of Korean Neurosurgical Society
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• 제29권10호
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• pp.1289-1295
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• 2000

Purpose : Recent evidence suggests a possible role for leukocytes in brain injury following ischemia and reperfusion. This study examined the temporal profile of ischemic tissue damage and leukocyte response after transient middle cerebral artery occlusion(MCAO) with reperfusion in the mouse. Methods : Focal cerebral ischemia was made by temporary occluding of the stem of the proximal MCA. Two groups of the mouse were investigated : (1) sham operation(n＝10), and (2)those having the arterial occlusion released after 90 minute(n＝20). By 4 hours(n＝10) and 24 hours(n＝10) after the onset of ischemia-reperfusion, fluorescein videoimages were under-taken in the pial venules of the mouse using a closed cranial window technique. Rhodamine 6G was administered as a $80-100{\mu}l/min$ i.v. loading dose and a $30-40{\mu}l/min$ i.v. maintenance dose in saline to selectively label circulating leukocytes. Neuropathologic evaluation for brain injury was accomplished using the histochemical stain 2,3,5-triphen-yltetrazolium chloride(TTC) and hematoxylin and eosin(H & E) stain. Results : The mean number of adherent leukocytes to cerebral venules in the 90 minutes MCAO and 24 hours reperfusion group were $306{\pm}24$ compared with $72{\pm}8$ in the sham operation group. In the TTC staining method, the cortical infarct affecting 34.8% of hemispheric volume were created in all of animals (n＝10) undergoing 90 minute MCAO with 24 hours reperfusion, but the infarcted area were not found in the other(sham operation and 90 minute MCAO with 4 hours reperfusion)groups. In the H & E stain, the brain tissue following 90 minute MCAO with 4 hours reperfusion revealed only a pyknosis of the nuclei with shrunken cytoplasm, but infiltrated leukocytes were not observed. After 24 hours of reperfusion, a many leukocytes were infiltrated within parenchyma and blood vessles. Conclusions : These findings demonstrate the feasiblity of continous in vivo monitoring of leukocyte adherence in cerebral venules and suggest that reperfusion induced leukocyte adherence to venular endothelium may contribute to tissue injury following focal cerebral ischemia.