• The Korean Journal of Physiology and Pharmacology
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• 제5권3호
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• pp.205-212
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• 2001

It has been proposed that nitirc oxide is involved in the pathogenesis of cerebral ischemia-reperfusion. Because superoxide production is also enhanced during reperfusion, the cytotoxic oxidant peroxynitrite could be formed, but it is not known if this occurs following global forebrain ischemia-reperfusion. We examined whether peroxynitrite generation is increased in the vulnerable regions after forebrain ischemia-reperfusion. Transient forebrain ischemia was produced in the conscious rat by four-vessel occlusion. Rats were subjected to 10 or 15 min of forebrain ischemia. Immunohistochemical method was used to detect 3-nitrotyrosine, a marker of peroxynitrite production. 3-Nitrotyrosine immunoreactivity was enhanced in the hippocampal CA1 area 3 days after reperfusion. Furthermore, in rats subjected to ischemia for 15 min, this change was also observed in the lateral striatal region and the lateral septal nucleus $2{\sim}3$ days after reperfusion. The cresyl violet staining of adjacent sections showed that neuronal cell death was induced in parallel with the nitrotyrosine immunoreactivity in the hippocampal CA1 area and the lateral striatal region. Our findings suggest that oxygen free radical accumulation and consequent peroxynitrite production play a role in neuronal death caused by cerebral ischemia-reperfusion.

• The Korean Journal of Physiology and Pharmacology
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• 제20권2호
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• pp.185-192
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• 2016

Ampicillin, a ${\beta}$-lactam antibiotic, dose-dependently protects neurons against ischemic brain injury. The present study was performed to investigate the neuroprotective mechanism of ampicillin in a mouse model of transient global forebrain ischemia. Male C57BL/6 mice were anesthetized with halothane and subjected to bilateral common carotid artery occlusion for 40 min. Before transient forebrain ischemia, ampicillin (200 mg/kg, intraperitoneally [i.p.]) or penicillin G (6,000 U/kg or 20,000 U/kg, i.p.) was administered daily for 5 days. The pretreatment with ampicillin but not with penicillin G significantly attenuated neuronal damage in the hippocampal CA1 subfield. Mechanistically, the increased activity of matrix metalloproteinases (MMPs) following forebrain ischemia was also attenuated by ampicillin treatment. In addition, the ampicillin treatment reversed increased immunoreactivities to glial fibrillary acidic protein and isolectin B4, markers of astrocytes and microglia, respectively. Furthermore, the ampicillin treatment significantly increased the level of glutamate transporter-1, and dihydrokainic acid (DHK, 10 mg/kg, i.p.), an inhibitor of glutamate transporter-1 (GLT-1), reversed the neuroprotective effect of ampicillin. Taken together, these data indicate that ampicillin provides neuroprotection against ischemia-reperfusion brain injury, possibly through inducing the GLT-1 protein and inhibiting the activity of MMP in the mouse hippocampus.

• 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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• 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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• 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 1995년도 춘계학술대회
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• pp.35-36
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• 1995

To gain insight into the etiological mechanism of dementia and to develop clinically effective congnitive enhancers, it is required to prepare animal models with symptoms and mechanism resemble to that in human. Dementia is mainly classified into two types : senile type of Alzheimer's disease (STAD) and cerebral ischemia-induced one. As animal models of cerebral ischemia, a couple of types in rats have been introduced : one is the occlusion of bilateral carotid arteries-induced forebrain/global ischemia and the other is the occlusion of middle cerebral arteries-induced focal/regional ischemia.

• 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.

• 국제물리치료학회지
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• 제2권2호
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• pp.281-287
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• 2011

This research was attempted to seek for a positive approach within the framework of physical therapy instead of the drug treatment in the past, with regard to the ischemic brain injury in the early stage. Accordingly, the aim of this research is to observe the change of HSP27 and HSP70, the genes that are expressed in the early stage of brain injury and to investigate the effects of needle electrode electrical stimulation(NEES), upon applying NEES after ischemia. The experimental method is to give rise to global ischemia and apply NEES to 27 SD-Pat rats with the particulars of being eight-week-old, male, around 300g, and adapted to laboratory environment for more than a week, and divide them into three groups, that is, GV20 NEES group(n=9), L14 NEES group(n=9), no applied NEES global ischemia(GI) group(n=9), and then observe their changes of HSP27 and HSP70 at the time lapse of 6, 9 hr and 12 hr after ischemia, using immunohistochemistry methods. Upon observing through the immunohistochemistry method, it was noticed that there was a significant difference between the GV20 NEES group and the L14 NEES group as for HSP27 and there were significant differences among all groups as for HSP70(p<.05). Accordingly, it is supposed that the application of NEES after the outbreak of cerebral ischemia delay the apoptosis in the early ischemic part of forebrain or protect neurons against apoptosis.

• 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.

• 동의신경정신과학회지
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• 제21권1호
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• pp.59-69
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• 2010

Objectives: The study aims to look into how the application of EA(Electro-acupuncture) in the initial step of ischemic brain injury affects the changes in Bax and Caspase-3 expression among forebrain apoptosis. Methods: It caused GI by using common carotid artery occlusion and conducted the test by dividing into the no applied EA group after 6 hours and 12 hours, the LI 4 EA group that applied EA to LI4, and GV 20 EA group that was applied to GV 20. After that, the following results were obtained by comparing Bax and Caspase-3 expression, which were apoptosis-related factors, with its application time through immunohistochemical staining after extracting brain of each group. Results: According to each group's Bax expression by the application time, the order of expression increase after 6 hours is shown to be the no applied EA group, LI 4 group, and GV 20 group. The stimulation after 12 hours was most lowly expressed in the GV 20 group, and the no applied EA group and LI 4 group showed similar level. Conclusions: EA stimulation in the initial step after ischemia seems to affect positively Bax and Caspase-3 expression that are index of forebrain apoptosis.