• The Korean Journal of Physiology and Pharmacology
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• 제10권4호
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• pp.167-172
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• 2006

In the present study, we developed a simple method to predict the neuronal cell death in the mouse hippocampus and striatum following transient global forebrain ischemia by evaluating both cerebral blood flow and the plasticity of the posterior communicating artery (PcomA). Male C57BL/6 mice were anesthetized with halothane and subjected to bilateral occlusion of the common carotid artery (BCCAO) for 30 min. The regional cerebral blood flow (rCBF) was measured by laser Doppler flowmetry. The plasticity of PcomA was visualized by intravascular perfusion of India ink solution. When animals had the residual cortical microperfusion less than 15% as well as the smaller PcomA whose diameter was less than one third compared with that of basilar artery, neuronal damage in the hippocampal subfields including CA1, CA2, and CA4, and in the striatum was consistently observed. Especially, when mice met these two criteria, marked neuronal damage was observed in CA2 subfield of the hippocampus. In contrast, after transient BCCAO, neuronal damage was consistently produced in the striatum, dependent more on the degree of rCBF reduction than on the plasticity of PcomA. The present study provided simple and highly reproducible criteria to induce the neuronal cell death in the vulnerable mice brain areas including the hippocampus and striatum after transient global forebrain ischemia.

• The Korean Journal of Physiology and Pharmacology
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• 제4권1호
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• pp.73-79
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• 2000

This study investigated whether propofol, an intravenous, non-barbiturate anesthetic, could reduce brain damage following global forebrain ischemia. Transient global ischemia was induced in gerbils by occlusion of bilateral carotid arteries for 3 min. Propofol (50 mg/kg) was administered intraperitoneally 30 min before, immediately after, and at 1 h, 2 h, 6 h after occlusion. Thereafter, propofol was administered twice daily for three days. Treated animals were processed in parallel with ischemic animals receiving 10% intralipid as a vehicle or with sham-operated controls. In histologic findings, counts of viable neurons were made in the pyramidal cell layer of the hippocampal CA1 area 4 days after ischemia. The number of viable neurons in the pyramidal cell layer of CA1 area was similar in animals treated with a vehicle or a subanesthetic dose of propofol. In terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling (TUNEL) assay, semiquantitative analysis of dark-brown neuronal cells was made in the hippocampal CA1 area. There was no significant difference in the degree of TUNEL staining in the hippocampal CA1 area between vehicle-treated and propofol-treated animals. These results show that subanesthetic dose of propofol does not reduce delayed neuronal cell death following transient global ischemia in Mongolian gerbils.

• The Korean Journal of Physiology and Pharmacology
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• 제12권6호
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• pp.287-291
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• 2008

Ampicillin, a $\beta$-lactam antibiotic, has been reported to induce astrocytic glutamate transporter-l which plays a crucial role in protecting neurons against glutamate excitotoxicity. We investigated the effect of ampicillin on neuronal damage in the mouse hippocampus and neostriatum following transient global forebrain ischemia. Male C57BL/6 mice were anesthetized with halothane and subjected to bilateral occlusion of the common carotid artery for 40 min. Ampicillin was administered post-ischemically (for 3 days) and/or pre-ischemically (for $3{\sim}5$ days until one day before the onset of ischemia). Pre- and post-ischemic treatment with ampicillin (50 mg/kg/day or 200 mg/kg/day) prevented ischemic neuronal death in the medial CAI area of the hippocampus as well as the neostriatum in a dose-dependent manner. In addition, ischemic neuronal damage was reduced by pre-ischemic treatment with ampicillin (200 mg/kg/day). In summary, our results suggest that ampicillin plays a functional role as a chemical preconditioning agent that protects hippocampal neurons from ischemic insult.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2000년도 춘계학술대회
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• pp.15-16
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• 2000

Transient forebrain ischemia results in delayed neuronal death in the CA1 region of the hippocampus after injury, which is, at least in part, a consequence of excessive generation of reactive oxygen species. Previous in vitro studies using cell cultures or brain slices have demonstrated that phospholipase D (PLD) in the nervous system is involved in the signaling mechanism in response to a variety of agonists. Several recent studies have shown that reactive oxygen species stimulate phospholipase D (PLD) activity in several kinds of cells. Therefore, this raises the possibility that PLD activity is enhanced in the ischemic brain. Meanwhile, osteopontin (OPN) was initially identified as a sialoglycoprotein in bone, but has since been found in various tissues. Although not much is known about its function, OPN seems to play an important role in inflammation and tissue repair. Recently, it was reported that OPN was upregulated in the activated microglia after focal brain ischemia, suggesting that OPN might play a role in wound healing after a focal stroke.

• The Korean Journal of Physiology and Pharmacology
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• 제26권1호
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• pp.47-57
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• 2022

Stiripentol is an anti-epileptic drug for the treating of refractory status epilepticus. It has been reported that stiripentol can attenuate seizure severity and reduce seizure-induced neuronal damage in animal models of epilepsy. The objective of the present study was to investigate effects of post-treatment with stiripentol on cognitive deficit and neuronal damage in the cornu ammonis 1 (CA1) region of the hippocampus proper following transient ischemia in the forebrain of gerbils. To evaluate ischemia-induced cognitive impairments, passive avoidance test and 8-arm radial maze test were performed. It was found that post-treatment with stiripentol at 20 mg/kg, but not 10 or 15 mg/kg, reduced ischemia-induced memory impairment. Transient ischemia-induced neuronal death in the CA1 region was also significantly attenuated only by 20 mg/kg stiripentol treatment after transient ischemia. In addition, 20 mg/kg stiripentol treatment significantly decreased ischemia-induced astrocyte damage and immunoglobulin G leakage. In brief, stiripentol treatment after transient ischemia ameliorated transient ischemia-induced cognitive impairment in gerbils, showing that pyramidal neurons were protected and astrocyte damage and blood brain barrier leakage were significantly attenuated in the hippocampus. Results of this study suggest stiripentol can be developed as a candidate of therapeutic drug for ischemic stroke.

• Natural Product Sciences
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• 제15권4호
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• pp.198-202
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• 2009

Based on the use of Acorus gramineus SOLAND (AG) for the treatment of stroke in traditional Korean medicine, the present study was carried out to evaluate neuroprotective effects of ${\alpha}$-asarone after transient global cerebral ischemia using rat 4-vessel occlusion (4VO) model in rats. ${\alpha}$-Asarone (5 mg/kg) administered intraperitoneally significantly protected CA1 neurons against 10 min transient forebrain ischemia as demonstrated by measuring the density of neuronal cells stained with Cresyl violet. ${\alpha}$-Asarone significantly reduced hippocampal neuronal cell death by 85.2% where as its isolated single compounds from AG compared with a vehicle-treated group.

• Molecules and Cells
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• 제22권1호
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• pp.8-12
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• 2006

Neuron-derived orphan receptor (NOR-1) is a member of the thyroid/steroid receptor superfamily that was originally identified in forebrain neuronal cells undergoing apoptosis. In addition to apoptotic stimuli, activation of several signal transduction pathways including direct neuronal depolarization regulates the expression of NOR-1. In this study we tested whether the expression of NOR-1 is changed following transient ischemic injury in the adult rat brain. NOR-1 mRNA increased rapidly in the dentate gyrus of the hippocampal formation and piriform cortex 3 h after transient global ischemia and returned to basal level at 6 h. On the other hand, oxygen-glucose deprivation of cultured cerebral cortical neurons did not alter the expression of NOR-1. These results suggest that expression of NOR-1 is differentially regulated in different brain regions in response to globally applied brain ischemia, but that hypoxia is not sufficient to induce its expression.

• The Korean Journal of Physiology and Pharmacology
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• 제26권3호
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• pp.227-227
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• 2022

• The Korean Journal of Physiology and Pharmacology
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• 제2권3호
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• pp.279-286
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• 1998

It has been well documented that transient forebrain global ischemia causes selective neuronal degeneration in hippocampal CA1 pyramidal neurons with a delay of a few days. The mechanism of this delayed hippocampal CA1 pyramidal neuronal death (DND) is still controversial. To delineate the mechanisms of the DND, the effects of treatment with MK-801, an NMDA receptor antagonist, kynurenic acid, a NMDA/non-NMDA receptor antagonist, and/or cycloheximide, a protein synthesis inhibitor, on the DND were investigated in male Wistar rats. To examine the participation of apoptotic neuronal death in the DND, TUNEL staining was performed in ischemic brain section. Global ischemia was induced by 4-vessel occlusion for 20 min. All animals in this study showed the DND 3 and 7 days after the ischemic insult. The DND that occured 3 days and 7 days after the ischemia were not affected by pretreatment with MK-801 (1 mg/kg), but markedly attenuated by the pretreatment with kynurenic acid (500 mg/kg). Treatment with cycloheximide (1 mg/kg) also markedly inhibited the DND. The magnitudes of attenuation by the two drugs were similar. The magnitude of attenuation by co-treatments with kynurenic acid and cycloheximide was not greater than that with any single treatment. TUNEL staining was negative in the sections obtained 1 or 2 days after the ischemic insults, but it was positive at hippocampal CA1 pyramidal cells in sections collected 3 days after the ischemia. These results suggested that the DND should be mediated by the activation of non-NMDA receptor, not by the activation of NMDA receptor and that the activation of AMPA receptor should induce the apoptotic process in the DND.

• 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.