• Journal of Korean Neurosurgical Society
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• 제54권1호
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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.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1995년도 춘계학술대회
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• pp.38-40
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• 1995

There have reports suggested that cerebral blood flow (CBF) has decreased in patients with both senile dementia of the Alzheimer's type and multi-infarct dementia, which are characterized by marked cognitive impairments. In addition, recent studies have demonstrated that decrease of CBF precedes the onset of multi-infarct dementia. These findings further suggest that chronic reduction of CBF may play an important role in the formation and progression of cerebral vascular dementia. Although transient cerebral ischemia, based upon vascular “reperfusion”, is apparently not paralleling the clinical condition, the transient cerebral ischemia model is one of the major methods investigated and the other is the cerebral embolism operation. Cognitive impairment and neuronal damages have been fully studied using these transient and/or embolic ischemia models. There are, however, few investigations focused the attention on the influence of chronic decrease of CBF on cognitive processes. In the present study, we have chosen a chronic ischemic model which is produced by permanent occlusion of bilateral common carotid arteries (2VO) in rats to investigate the neuronal damage and cognitive deficits through radial maze performance. We investigated furtherly the effects of tetramethylpyrazine (TMP), a constituent isolated from Ligusticum Chuanxiong on such a model.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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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.

• 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.

• Biomolecules & Therapeutics
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• 제25권2호
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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.

• 동국한의학연구소논문집
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• 제11권
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• pp.58-65
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• 2008

Objectives : BHT has been commonly used to treatment of brain disorders in Oriental clinic in Korea. The purpose of this study was to determine the inhibitory effect of modified BHT-C extract on the transient forcal cerebral ischemia in rats. Method : We prepared ischemic rats by the transient middle cerebral artery occlution(MCAO; 90 min occlusion and 144 h reperfusion) in rat brains. BHT-C extract (100 and 200 mg/kg, i.p.) was administered every day after the onset of MCAO until 6 day. Result : BHT-C extract increased survival rate of ischemic rats compared with vehicle-treated rats. BHT-C extract treated rats (100 and 200 mg/kg) were shown a significant reduction in infarct volume compared with vehicle-treated rats. Conclusions : These results suggest that BHT-C extract may contribute to its protective effects in brain ischemia through the reduction of brain infarction.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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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)

• 대한간호학회지
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• 제34권1호
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• pp.150-159
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• 2004

Purpose: The purpose of this study was to determine the effect of DHEA on hindlimb muscles(soleus, plantaris and gastrocnemius) in a focal brain ischemia model rat. Method: Twenty-seven male Sprague-Dawley rats were randomly divided into three groups: CINS(cerebral ischemia + normal saline), CIDH(cerebral ischemia + DHEA), or SHNS(sham + normal saline). Both the CINS and CIDH groups underwent a transient right middle cerebral artery occlusion operation. In the SHNS group, a sham operation was done. 0.34mmol/kg DHEA was administered daily by an intraperitoneal injection for 7days. Results: The muscle weight, muscle fiber cross-sectional area of the Type I muscle fiber of soleus and Type II muscle fiber of plantaris and gastrocnemius, myofibrillar protein content of gastrocnemius, and muscle strength in the CINS group decreased compared with the SHNS group. The muscle weight, muscle fiber cross-sectional area of the Type II muscle fiber of plantaris and gastrocnemius, myofibrillar protein content of soleus, and muscle strength in the CIDH group increased compared with the CINS group. Conclusion: It was identified that muscle atrophy could be induced during 7 days after a cerebral infarction, and DHEA administration during the early stages of a cerebral infarction might attenuate muscle atrophy.

• 동의생리병리학회지
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• 제18권1호
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• pp.236-242
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• 2004

Cerebral ischemia resulting from transient or permanent occlusion of cerebral arteries leads to neuronal cell death and eventually causes neurological impairments. Bee venom has been used for the treatment inflammatory disease. In the present study, the effects of bee venom on apoptosis and cell proliferation in the hippocampal dentate gyrus following transient global ischemia in gerbils were investigated using immunohistochemistry for cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), caspase-3, and 5-bromo-2'-deoxyuridine (BrdU). It was shown that apoptotic cell death and cell proliferation in the hippocampal dentate gyrus were significantly increased following transient global ischemia in gerbils and that treatment of bee venom suppressed the ischemia-induced increase in apoptosis and cell proliferation in the dentate gyrus. The present results also showed that 1 mg/kg bee-venom treatment suppressed the ischemia-induced increasing apoptosis, cell proliferation, and COX-2 expression in the dentate gyrus. It is possible that the suppression of cell proliferation is due to the reduction of apoptotic cell death by treatment of bee venom. In the present study, bee venom was shown to prosses anti-apoptotic effect in ischemic brain disease, and this protective effect of bee venom against ischemia-induced neuronal cell death is closely associated with suppression on caspase-3 expression.

• 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.