• 한국약용작물학회지
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• 제22권1호
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• pp.46-52
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• 2014

In traditional Korean and Chinese medicine, safflower (Carthamus tinctorius L.) for the treatment of central nervous system-related symptoms such as tremor, seizure, stroke and epilepsy. We investigated the effects of safflower could influence cerebral ischemia-induced neuronal and cognitive impairments. Administration of safflower for 1 day (200 mg/kg body weight, p.o.) increased the survival of hippocampal CA1 pyramidal neurons after transient global brain ischemia. And neurological functions measured as short term memory. Post-treatment with safflower for 2 times decreased the induction/reduction - induced production of neuronal cell loss from global cerebral ischemia. Safflower markedly decreased neuronal cell death and also caused a decrease in the content of thiobarbituric acid-reacting substances (TBARS) ($55.2{\pm}9.4{\mu}mol\;mg^{-1}$) and significant improvement of activities of glutathione (GSH) ($27.2{\pm}5.0{\mu}mol\;mg^{-1}$) in hippocampus. We conclude that treatment with safflower attenuated learning and memory deficits, and neuronal cell loss induced by global cerebral ischemia. These results suggest that safflower may be a potential candidate for the treatment of vascular dementia.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2003년도 Annual Meeting of KSAP : International Symposium on Pharmaceutical and Biomedical Sciences on Obesity
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• pp.62-62
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• 2003

It is now convincing that free radical generation is involved in the pathophy siological mechanisms of ischemic stroke, particularly in ischemia-reperfusion injury. The present study, therefore, examined neuroprotective effect of aloesin isolated from Aloe vera, which was known to have antioxidative activity, in a rat model of transient focal cerebral ischemia. Transient focal cerebral ischemia was induced by occlusion of middle cerebral artery for 2 hr with a silicone-coated 4-0 nylon monofilament in male Sprague-Dawley rats under isoflurane anesthesia Aloesin (1, 3, 10, 30 and 50 mg/kg/injection) was administered intravenously 3 times at 0.5, 2 and 4 hr after onset of ischemia. Neurological score was measured 24 hr after onset of ischemia immediately before sacrifice. Seven serial coronal slices of the brain were stained with 2,3,5-triphenyltetrazolium chloride and infarct size was measured using a computerized image analyzer. Treatment with the close of 1 or 50 mg/kg did not significantly reduce infarct volume compared with the saline vehicle-treated control group. However, treatments with the closes of 3 and 10 mg/kg significantly reduced both infarct volume and edema by approximately 47% compared with the control group, producing remarkable behavioral recovery effect. Treatment with the close of 30 mg/kg also significantly reduced infarct volume to a lesser extent by approximately 33% compared with the control group, but produced similar degree of behavioral recovery effect. In addition, general pharmacological studies showed that aloesin was a quite safe compound. The results suggest that aloesin can serve as a lead chemical for the development of neuroprotective agents by providing neuroprotection against focal ischemic neuronal injury.

• 대한한의학회지
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• 제30권2호
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• pp.1-16
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• 2009

Objectives: This study investigated the effect of Yukmijihwangtang on cerebral ischemia-induced learning and memory impairment by middle cerebral artery (MCA) occlusion in rats. Methods: The ability of learning and memory of rats was measured using the eight-arm radial maze and the passive avoidance test, and profile of cholinergic neuron was assessed in the medial septum and hippocampus region by immuno-histochemistry. Results: 1. No differences were found between groups in the number of correct choices in acquisition performance during the eight-arm radial maze task. 2. No differences were found between groups on day 1 in the error rate in acquisition performance, which is defined as the number of enters into the same arm more than once within five minutes. After 5 to 6 days of test, the number of errors was significantly reduced in the Yukmijihwangtang group (forebrain ischemia group with Yukmijihwangtang treatment), compared with the ischemia group. 3. The memory processes significantly improved in the Yukmijihwangtang group according to results of the passive avoidance test. 4. The appearance of AchE (acetylcholinesterase) in the CA1 region of hippocampus significantly decreased in the ischemia group, compared with the sham group (untreated group). The appearance of AchE in the same region significantly increased in the Yukmijihwangtang group, compared with the ischemia group. 5. The appearance of ChAT (choline acetyltransferase) in the CA1 region of the hippocampus and medial septum decreased in the ischemia group, compared with the sham group. The appearance of ChAT in the same region significantly increased in the Yukmijihwangtang group, compared with the ischemia group Conclusions: This study provides evidence that Yukmijihwangtang is effective for reviving the ability of learning and memory and damaged neurons in rats with experimental cerebral ischemia.

• 한방재활의학과학회지
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• 제18권4호
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• pp.1-11
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• 2008

목적 : 뇌허혈은 일시적 혹은, 영구적 뇌동맥 폐색에 의한 뇌혈류의 감소로 유발되며, 허혈 부위에서는 복잡한 병태 생리적 과정을 통하여 신경 세포사가 초래되어 비가역적인 신경학적 손상을 일으킨다. 본 연구에서는 모래쥐를 대상으로 일시적인 전뇌허혈을 유발 시킨 후 해마 치상회에서 허혈로 인한 세포사멸을 관찰하고, 현삼(玄蔘)의 투여가 허혈로 유발된 해마 치상회에서 세포사멸에 미치는 영향과 단기 기억에 미치는 효과를 규명하고자 실험하였다. 연구방법 : 세포사멸은 DNA 분절을 나타내는 terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) 염색법과 단백분해 과정의 마지막 단계에 발현되는 caspase-3에 대한 면역조직화학법을 이용하였고, 단기기억은 step-down avoidance task를 실시하여 평가하였다. 결과 : 본 실험의 결과 일시적인 전뇌허혈은 해마 치상회의 세포사멸을 유의하게 증가시켰으며 단기기억을 감소시켰다. 현삼의 투여는 허혈로 증가된 해마 치상회의 세포사멸을 유의하게 억제하였고, 허혈로 인한 단기 기억의 감소를 유의하게 억제시켰다. 결론 : 본 실험을 통하여 현삼은 뇌허혈로 증가된 세포사멸을 억제하고 단기 기억을 향상시킴을 알 수 있었고, 따라서 현삼은 뇌허혈로 인한 뇌손상을 보호할 수 있는 효과가 있음을 제시하는 바이다.

• Molecules and Cells
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• 제20권3호
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• pp.354-360
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• 2005

Neuronal damage subsequent to transient cerebral ischemia is a multifactorial process involving several overlapping mechanisms. Gangliosides, sialic acid-conjugated glycosphingolipids, reduce the severity of acute brain damage in vitro. However their in vivo effects on the cerebral cortex damaged by ischemic infarct are unknown. To assess the possible protective role of gangliosides we examined their expression in the cerebral cortex damaged by ischemic infarct in the rat. Ischemia was induced by middle cerebral artery (MCA) occlusion, and the resulting damage was observed by staining with 2, 3, 5-triphenylterazolium chloride (TTC). High-performance thin-layer chromatography (HPTLC) showed that gangliosides GM3 and GM1 increased in the damaged cerebral cortex, and immunofluorescence microscopy also revealed a significant change in expression of GM1. In addition, in situ hybridization demonstrated an increase in the mRNA for ganglioside GM3 synthase. These results suggest that gangliosides GM1 and GM3 may be synthesized in vivo to protect the cerebral cortex from ischemic damage.

• Biomolecules & Therapeutics
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• 제25권4호
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• pp.383-389
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• 2017

Dexmedetomidine is an ${\alpha}2$-adrenergic receptor agonist that exhibits a protective effect on ischemia-reperfusion injury of the heart, kidney, and other organs. In the present study, we examined the neuroprotective action and potential mechanisms of dexmedetomidine against ischemia-reperfusion induced cerebral injury. Transient focal cerebral ischemia-reperfusion injury was induced in Sprague-Dawley rats by middle cerebral artery occlusion. After the ischemic insult, animals then received intravenous dexmedetomidine of $1{\mu}g/kg$ load dose, followed by $0.05{\mu}g/kg/min$ infusion for 2 h. After 24 h of reperfusion, neurological function, brain edema, and the morphology of the hippocampal CA1 region were evaluated. The levels and mRNA expressions of interleukin-$1{\beta}$, interleukin-6 and tumor nevrosis factor-${\alpha}$ as well as the protein expression of inducible nitric oxide synthase, cyclooxygenase-2, nuclear factor-${\kappa}Bp65$, inhibitor of ${\kappa}B{\alpha}$ and phosphorylated of ${\kappa}B{\alpha}$ in hippocampus were assessed. We found that dexmedetomidine reduced focal cerebral ischemia-reperfusion injury in rats by inhibiting the expression and release of inflammatory cytokines and mediators. Inhibition of the nuclear factor-${\kappa}B$ pathway may be a mechanism underlying the neuroprotective action of dexmedetomidine against focal cerebral I/R injury.

• 생약학회지
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• 제34권4호통권135호
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• pp.335-338
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• 2003

It is thought that highly reactive oxygen species generated after strokes plays a key role in damaging the brain. We examined free radical scavenging activity and neuroprotective effects of several medicinal herbs in a rat model of transient ischemia. Free radical scavenging property of medicinal herbs was examined in vitro using 1,1-diphenyl-2-picrylhydrazyl stable free radical. Transient ischemia was induced by intraluminal occlusion of the right middle cerebral artery for 120 min, followed by reperfusion for 22 hr in rats. Aqueous extracts of 8 medicinal herbs (200 mg/kg) were orally administered twice to transient ischemic rat prior to reperfusion and 2 hr after reperfusion. Total infarction volume in the hemisphere ipsilateral to the ischemia-reperfusion was significantly decreased in 7 groups treated with Sophora flavescens, Lycopus lucidus, Sanguisorba officinalis, Caesalpinia sappan, Albizia julibrissin, Rubia akane, Psoralea corylifolia, or Prunella vulgaris. However, neuroprotective effects of these medicinal herbs were not correlated with their antioxidative activities. These results suggest that these medicinal herbs exert neuroprotection via antioxidative as well as unknown mechanism.

• 한방재활의학과학회지
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• 제21권2호
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• pp.1-13
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• 2011

Objectives : We investigated the effect of Haein-tang(Hairen-tang) on short-term memory and apoptosis in dentate gyrus of the gerbils with transient global ischemia. Methods : For the induction of cerebral ischemia model in mice, common carotid arteries of gerbils were occluded with aneurysm clips for 5 min. One day after operation, Haein-tang(Hairen-tang) was administrated orally injected once a day for 15 consecutive days. Gerbils were randomly divided into four group(n=10 in each group): sham-operation group, ischemia-induction group, ischemia-induction and 50 mg/kg Haein-tang(Hairen-tang)-treated group, ischemia-induction and 100 mg/kg Haein-tang(Hairen-tang)-treated group, and ischemia-induction and 200 mg/kg Haein-tang(Hairen-tang)-treated group. The effect of Haein-tang(Hairen-tang) on memory function was investigated by using step-down avoidance task. Apoptosis was confirmed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) staining and immunohistochemistry for caspase-3. Western blot analysis for the expressions of Bax and Bcl-2 protein was also conducted. Results : 1. Haein-tang extract significantly enhanced short-term memory in step-down avoidance task and 100 mg/kg, 200 mg/kg Haein-tang-treated group. 2. Haein-tang extract significantly suppressed TUNEL-positive cells after transient global ischemia and 50 mg/kg, 100 mg/kg, 200 mg/kg Haein-tang-treated group. 3. Haein-tang extract significantly increased caspase-3 positive cells in the hippocampal dentate gyrus after transient global ischemia and 50 mg/kg, 100 mg/kg, 200 mg/kg Haein-tang-treated group. 4. Haein-tang extract significantly decreased Bax protein expressions in the hippocampus after transient global ischemia and 100 mg/kg, 200 mg/kg, Haein-tang-treated group. Haein-tang extract significantly increased Bcl-2 protein expressions in the hippocampal dentate gyrus after transient global ischemia and 50 mg/kg, 100 mg/kg, 200 mg/kg, Haein-tang-treated group. Haein-tang extract significantly decreased Ratio of Bax protein to Bcl-2 protein in the hippocampus after transient global ischemia and 100 mg/kg, 200 mg/kg Haein-tang-treated group. Conclusions : While Haein-tang(Hairen-tang) treatment improved short-term memory by suppressing on ischemia-induction apoptosis. In the present study, Haein-tang(Hairen-tang) shows protective effect on transient global ischemia.

• 동의생리병리학회지
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• 제25권2호
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• pp.300-305
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• 2011

The present study was investigated the neuroprotective effects of acupuncture at ST36 on learning and memory deficits after transient cerebral ischemia in a gerbil model. The animals were randomly divided into three groups (n=7 in each group): the sham operation group (SHAM), ischemia-induced and ST36 acupuncture group (ISC + ST36), and the ischemia-induced and Tail-acupuncture group (ISC + TAIL). For the acupuncture stimulation, stainless steel needles, 0.3 mm in diameter, were inserted bilaterally into the ST36 locus or the tail and stimulated for 1 min/day for 14 days. Using the Morris water maze test, the animals were tested on spatial learning and memory. In addition, the effects of acupuncture on memory storage and the choline acetyltransferase (ChAT) activity, in the hippocampal CA1 area, were investigated by ChAT immunohistochemistry. Transient cerebral ischemia produced impaired performance on the MWM test (DAY 5: p<0.01 and retention test: p<0.05) and severely decreased ChAT immunoreactivity in the CA1 hippocampal area compared to the SHAM group (p<0.05). However, improved learning and memory were observed (DAY 5: p<0.05 and retention test: p<0.01) as well as a significantly reduced loss of ChAT immunoactivity in the hippocampal CA1 region (p<0.001) after acupuncture stimulation at ST36 were observed. These results show that acupuncture at ST36 ameliorated the learning and memory deficits at least in part through the cholinergic system. The findings of this study provide potential data that acupuncture is useful for the treatment of some of the behavioral impairs of transient cerebral ischemia.

• The Korean Journal of Physiology and Pharmacology
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• 제1권6호
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• pp.665-672
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• 1997

This study aimed to investigate the mechanism of cerebroprotection of platelet-activating factor(PAF) antagonists in transient cerebral ischemia of rat. Right middle cerebral artery(MCA) of Sprague-Dawley rat was occluded for 2 hours using an intraluminal filament technique. After 22 hours of reperfusion, morphometrically detectable infarct was developed in the cortex and striatum identical to the territory of MCA. The infarct size was significantly reduced by PAF antagonists, BN 52021 and CV-6209, as well as an inducible nitric oxide synthase(iNOS) inhibitor aminoguanidine(1 mg/kg, i.p., respectively) administered 5 min after MCA occlusion. PAF antagonists significantly inhibited the enzymatic activities of both myeloperoxidase and iNOS in the cerebral hemisphere ipsilateral to ischemia, whereas aminoguanidine did not inhibit myeloperoxidase activity but significantly inhibited the iNOS activity. These results suggest that PAF antagonists exert a cerebroprotective effect against ischemic brain damage through inhibition of leukocyte infiltration and iNOS activity in the postischemic brain.