• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.6
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• pp.1777-1783
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• 2004

This study was conducted to determine the effects Wonjiseokchangpo-san on brain damage in transient focal cerebral ischemia. Rats were used for testing in the following three models: Morris Water Maze, Eight-Arm Radial Maze, and Histochemistry. In the Morris Water Maze Model, the Wonjiseokchangpo-san group showed significant decrease in the 3rd and 6th training session compared with the ischemia group. A retention test, in the Morris Water Maze Model, was performed on the 7th day without the escape platform. The Wonjiseokchangpo-san group showed significant increase compared to the ischemia group. In the Eight-Arm radial Maze model, the Wonjiseokchangpo-san group showed significant decrease in the error rate compared to the ischemia group. In the density of hippocampal CA1 cell of the cresyl violet-stained section, the Wonjiseokahangpo-san group showed significant increase compared to the ischemia group. These results suggest that Wonjiseokchangpo-san may have a significant protective effect on brain damage and cognitive dysfunction in transient focal cerebral ischemia.

• The Journal of Korean Medicine
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• v.26 no.2 s.62
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• pp.52-62
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• 2005

Objectives: This study was conducted to determine the effects of Geupunggibodan on brain damage in transient focal cerebral ischemia in rats. Methods: Rats were used for testing in the following three models: Morris water maze, eight-ann radial maze, and histochemistry. Results: In the Morris water maze model, the Geupunggibodan group showed significant decrease in the 3rd, 4th and 6th training sessions compared with the ischemia, group. A retention test in the Morris water maze model was performed on the 7th day without the escape platform. The Geupunggibodan group showed significant increase compared to the ischemia group. In the eight-ann radial maze model, the Geupunggibodan group showed significant decrease in the error rate compared to the ischemia group. In the density of hippocampal CA1 cell of the cresyl violet-stained section, the Geupunggibodan group showed significant increase compared to the ischemia group. Conclusions: These results suggest that Geupunggibodan may have a significant protective effect on brain damage and cognitive dysfunction in transient focal cerebral ischemia.

• Biomedical Science Letters
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• v.11 no.2
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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.

• 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.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.303.1-303.1
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• 2002

Recent studies have suggested that the cerebral ischemia induced the neuronal cell death by mediating multiple mechanisms with necrosis and/or apoptosis. The present study examined neuroprotective mechanism of aloesin against transient focal cerebral ischemia. Aloesin. main component of aloe possesses various biological activates such as wound healing. anti-gastric ulcer. and chemopreventive activity. Transient focal cerebral ischemia was induced by 120 min MCAO. (omitted)

• Journal of Korean Neurosurgical Society
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• v.54 no.1
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• pp.1-7
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• 2013

Objective : This study was undertaken in the belief that the atypical antipsychotic drug quetiapine could prevent apoptosis in the penumbra region following ischemia, taking into account findings that show 5-hydroxytryptamine-2 receptor blockers can prevent apoptosis. Methods : We created 5 groups, each containing 6 animals. Nothing was done on the K-I group used for comparisons with the other groups to make sure adequate ischemia had been achieved. The K-II group was sacrificed on the 1st day after transient focal cerebral ischemia and the K-III group on the 3rd day. The D-I group was administered quetiapine following ischemia and sacrificed on the 1st day while the D-II group was administered quetiapine every day following the ischemia and sacrificed on the 3rd day. The samples were stained with the immunochemical TUNEL method and the number of apoptotic cells were counted. Results : There was a significant difference between the first and third day control groups (K-II/K-III : p=0.004) and this indicates that apoptotic cell death increases with time. This increase was not encountered in the drug groups (D-I/D-II : p=1.00). Statistical analysis of immunohistochemical data revealed that quetiapine decreased the apoptotic cell death that normally increased with time. Conclusion : Quetiapine is already in clinical use and is a safe drug, in contrast to many substances that are used to prevent ischemia and are not normally used clinically. Our results and the literature data indicate that quetiapine could help both as a neuronal protector and to resolve neuropsychiatric problems caused by the ischemia in cerebral ischemia cases.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.215-215
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• 1996

The present study examined chronic effects of transient focal cerebral ischemia on the substantia nigra, a remote exofocal area, using immunohistochenmical and receptor autoradiographic techniques. Transient focal cerebral ischemia was induced by middle cerebral artery (MCA) occlusion for 60 or 90 min followed by reperfusion using silicone-coated 4-0 nylon monofilament in male Wistar rats. After 1- or 2-week reperfusion following transient MCA occlusion, there were partial losses of tyrosine hydroxylase-immunoreactive dopaminergic neurons, incieases in glial fibrillary acidic protein-immunoreactive cells (gliosis), decreases in [$^3$H]YM-09151-2 binding for dopamine D$_2$ receptors, and marked atrophy in the ipsilateral substantia nigra. The precise mechanism(s) of exofocal damage to the substantia nigra is remained to be elucidated.

• Biomolecules & Therapeutics
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• v.25 no.2
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• pp.149-157
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• 2017

The interleukin-1 receptor antagonist (IL-1RA) is a potential stroke treatment candidate. Intranasal delivery is a novel method thereby a therapeutic protein can be penetrated into the brain parenchyma by bypassing the blood-brain barrier. Thus, this study tested whether intranasal IL-1RA can provide neuroprotection and brain penetration in transient cerebral ischemia. In male Sprague-Dawley rats, focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 1 h. The rats simultaneously received 50 mg/kg human IL-1RA through the intranasal (IN group) or intraperitoneal route (IP group). The other rats were given 0.5 mL/kg normal saline (EC group). Neurobehavioral function, infarct size, and the concentration of the administered human IL-1RA in the brain tissue were assessed. In addition, the cellular distribution of intranasal IL-1RA in the brain and its effect on proinflammatory cytokines expression were evaluated. Intranasal IL-1RA improved neurological deficit and reduced infarct size until 7 days after MCAO (p<0.05). The concentrations of the human IL-1RA in the brain tissue 24 h after MCAO were significantly greater in the IN group than in the IP group (p<0.05). The human IL-1RA was confirmed to be co-localized with neuron and microglia. Furthermore, the IN group had lower expression of $interleukin-1{\beta}$ and tumor necrosis $factor-{\alpha}$ at 6 h after MCAO than the EC group (p<0.05). These results suggest that intranasal IL-1RA can reach the brain parenchyma more efficiently and provide superior neuroprotection in the transient focal cerebral ischemia.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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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.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.305.1-305.1
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• 2002

The temporal profiles of the changes of dopaminergic cell and microglial activation induced by transient cerebral ischemia was investigated in the substantia nigral region which lay outside ischemic areas of rat brain after middle cerebral artery occlusion (MCAO). Transient cerebral ischemia was induced by intraluminal occlusion of the right middle cerebral artery for 2 hand reperfusion was continued for 1, 2. 3. 7. 10. 14. 30, 60. and 120 days. Activated microglial cells were visualized with immunohistochmistry using OX-43 antibody. (omitted)