• 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.

• 동의생리병리학회지
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• 제22권2호
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• pp.321-327
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• 2008

This study evaluated neuroprotective effects of Yanggyuksanhwa-tang (YST) on global cerebral ischemia of diabetic rats. On primary experiment, diabetic condition in rats was induced by streptozotocin injection. Secondarily, global cerebral ischemia was induced by bilateral occlusion of the common carotid artery with hypotension (BCAO) under the diabetic condition. Then neuroprotective effect of YST was observed with changes of neuronal c-Fos and Bax expressions, and GFAP expression in the brain tissues by using immunohistochemistry. YST treatment was resulted significant decrease of c-Fos expression in CA1 hippocampus induced by BCAO on diabetic rats. YST treatment was resulted significant decrease of Bax expression in CA1 hippocampus induced by BCAO on diabetic rats. YST treatment was resulted significant decrease of c-Fos expression in cerebral cortex and caudoputamen induced by BCAO on diabetic rats. YST treatment was resulted significant decrease of GFAP expression in cerebral cortex induced by BCAO on diabetic rats. These results suggest that YST has effects on neuroprotection against cerebral ischemic damage under diabetic condition. And it is supposed that neuroprotective effect of YST reveals by anti-apoptosis mechanism.

• 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.

• Journal of Korean Neurosurgical Society
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• 제58권6호
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• pp.508-512
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• 2015

Background : Cerebral ischemia is as a result of insufficient cerebral blood flow for cerebral metabolic functions. Resveratrol is a natural phytoalexin that can be extracted from grape's skin and had potent role in treating the cerebral ischemia. Apoptosis, a genetically programmed cellular event which occurs after ischemia and leads to biochemical and morphological changes in cells. There are some useful markers for apoptosis like Bcl-2, bax, and p53. The last reports, researchers verify the apoptosis with early markers like Annexin V. Methods : We preferred in this experimental study a model of global cerebral infarction which was induced by bilateral common carotid artery occlusion method. Rats were randomly divided into 4 groups : sham, ischemia-reperfusion (I/R), I/R plus 20 mg/kg resveratrol and I/R plus 40 mg/kg resveratrol. Statistical analysis was performed using Sigmastat 3.5 ve IBM SPSS Statistics 20. We considered a result significant when p<0.001. Results : After administration of resveratrol, Bcl-2 and Annexin levels were significantly increased (p<0.001). Depending on the dose of resveratrol, Bcl2 levels increased, p53 levels decreased but Annexin V did not effected. P53 levels were significantly increased in ishemia group, so apoptosis is higher compared to other groups. Conclusion : In the acute period, Annexin V levels misleading us because the apoptotic cell counts could not reach a certain level. Therefore we should support our results with bcl-2 and p53.

• Preventive Nutrition and Food Science
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• 제19권3호
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• pp.145-155
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• 2014

Vascular dementia is characterized by white matter lesions involving the demyelination and activation of astrocytes and microglia. In a previous study, we showed that the supernatant of a laboratory-scale, hot water extract of ground whole wheat (TALE) attenuated white matter injury and astrocytic activation in a rat model of bilateral common carotid artery occlusion (BCCAO). In the present study, we made several modifications to the hot water extraction process to remove starch and enable large-scale production. We used wheat bran (WB), which contains less starch, instead of ground whole wheat. In addition, we removed starch granules with a decanter before hot water extraction. The final product, wheat bran extract (WBE), contained 2.42% arabinose, a surrogate marker of arabinoxylan, which is an active constituent of WBE. Supplementation of the rat model of BCCAO with WBE (400 mg/kg/day) for 33 days attenuated white matter injury, which was assessed by Luxol Fast Blue staining, in the corpus callosum (cc) and optic tract (opt) regions. Attenuation of white matter injury in the opt region was accompanied by improvement of the pupillary light reflex. Immunochemical staining revealed that supplementation with WBE reduced astrocytic activation in the cc and opt regions and reduced microglial activation in the opt region. These findings indicate that supplementation with WBE is effective at attenuating white matter injury accompanied by the inhibition of astrocytic and microglial activation. Therefore, extracts from WB, a cheap by-product of wheat milling, can be developed as a nutraceutical to prevent vascular dementia, a disease for which there is no approved pharmaceutical treatment.

• 대한한방내과학회지
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• 제25권4호
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• pp.105-116
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• 2004

Objective : In this study, we used the aged bilateral common carotid artery occlusion (BCAO) rats were used to measure the effect of Bupleuri Radix (Si-Ho) on the brain ischemic injury, because aging is an important factor in storke, Method : The brian ischemic injury was induced by temporary closing of carotids on both sides in a low blood pressure state. Bupleuri Radix (Si-Ho) was orally administered in 18-month-old BCAO rats. Result : The Ischemic Damaged Hippocampus and HSP expression were analyzed by the immunohistochemical staining and the result were as follows: 1. The low numbers of pyramid cells in the hippocampus CA1 area for the ischemically injured experimental group rose to numbers simillar to those of the control group. 2. The thin neuronal cell layer in the hippocampus CA1 area for the ischemically injured experimental group returned to thickness simillar to those of the control group. 3. The normalized optical density of HSP70 expression was suppressed in CA2, DG and CA1 expression was significantly suppressed in the experimental group compared to the control group. Conclusion : These results suggested that Bupleuri Radix (Si-Ho) has a neuroprotective effect by reducing neural cell injury in the initial ischemic state.

• 대한간호학회지
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• 제49권3호
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• pp.317-328
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• 2019

Purpose: The purpose of this study was to identify the effect of ghrelin on memory impairment in a rat model of vascular dementia induced by chronic cerebral hypoperfusion. Methods: Randomized controlled groups and the posttest design were used. We established the representative animal model of vascular dementia caused by bilateral common carotid artery occlusion and administered $80{\mu}g/kg$ ghrelin intraperitoneally for 4 weeks. First, behavioral studies were performed to evaluate spatial memory. Second, we used molecular biology techniques to determine whether ghrelin ameliorates the damage to the structure and function of the white matter and hippocampus, which are crucial to learning and memory. Results: Ghrelin improved the spatial memory impairment in the Y-maze and Morris water maze test. In the white matter, demyelination and atrophy of the corpus callosum were significantly decreased in the ghrelin-treated group. In the hippocampus, ghrelin increased the length of hippocampal microvessels and reduced the microvessels pathology. Further, we confirmed angiogenesis enhancement through the fact that ghrelin treatment increased vascular endothelial growth factor (VEGF)-related protein levels, which are the most powerful mediators of angiogenesis in the hippocampus. Conclusion: We found that ghrelin affected the damaged myelin sheaths and microvessels by increasing angiogenesis, which then led to neuroprotection and improved memory function. We suggest that further studies continue to accumulate evidence of the effect of ghrelin. Further, we believe that the development of therapeutic interventions that increase ghrelin may contribute to memory improvement in patients with vascular dementia.

• 대한본초학회지
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• 제29권6호
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• pp.73-83
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• 2014

Objectives : This study was investigated the effects of the root of Polygala tenuifolia (POL) on learning and memory impairment induced by chronic cerebral hypoperfusion in rats. Methods : Chronic cerebral hypoperfusion was produced by permanent bilateral common carotid artery occlusion (pBCAO). POL was administered orally once a day (130 mg/kg of water-extract) for 28 days starting at 4 weeks after the pBCAO. The acquisition of learning and the retention of memory were tested on 9th week after the pBCAO using the Morris water maze. In addition, effects of POL on $A{\beta}$ generation and expressions of APP and BACE1 were observed in the hippocampus of rats. Results : POL significantly prolonged the swimming time spent in target quadrant and significantly reduced the swimming time spent in the quadrant far from the target. POL significantly increased the percentage of swim in the targer quadrant in the retention test, while POL was not effective on the escape latencies in the acquisition training trials. POL significantly reduced the levels of $A{\beta}_{(1-40)}$ and $A{\beta}_{(1-42)}$ in the cerebral cortex and the level of $A{\beta}_{(1-42)}$ in the hippocampus produced by chronic cerebral hypoperfusion. POL also significantly attenuated the up-regulation of APP and BACE1 expression in the hippocampus produced by chronic cerebral hypoperfusion. Conclusions : The results show that POL alleviated memory deficit and up-regulation of $A{\beta}$ and BACE1 expressions in the hippocampus. This result suggests that POL may exert ameliorating effect on memory deficit through inhibition of ${\beta}$-secretase activity and $A{\beta}$ generation.

• 대한본초학회지
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• 제31권1호
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• pp.7-15
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• 2016

Objectives : Polygalae Radix (POL) has an ameliorating effect on learning and memory impairment caused by cerebral hypoperfusion. In regard to POL's action mechanism, this study was carried out to investigate the effects of POL on oxidative damage and neuronal apoptosis induced by cerebral hypoperfusion in rats.Methods : The cerebral hypoperfusion was induced by permanent bilateral common carotid artery occlusion (pBCAO) in Sprague-Dawley rats. POL was administered orally once a day (130 mg/kg of water-extract) for 28 days starting at 4 weeks after the pBCAO. Superoxide dismutase (SOD) activities and malondialdehyde (MDA) levels in the brain tissue were measured using ELISA method. Expressions of 4-hydroxynonenal (4HNE) and 8-hydroxy-2'- deoxyguanosine (8-OHdG) were observed using immunohistochemistry. In addition, neuronal apoptosis was evaluated with Cresyl violet staining, TUNEL labeling, and immunohistochemistry against Bax and caspase-3.Results : POL treatment significantly increased SOD activities and significantly reduced MDA levels in the cerebral cortex. The up-regulations of 4HNE and 8-OHdG expression caused by pBCAO in the CA1 of hippocampus were significantly attenuated by POL treatment. POL treatment also restored the reduction of CA1 thickness and CA1 neurons caused by pBCAO and significantly attenuated the apoptotic markers including TUNEL-positive cells, Bax, and caspase-3 expression in the CA1 of hippocampus.Conclusions : The results show that POL attenuated the oxidative damage in brain tissue and neuronal apoptosis in the hippocampus caused by the cerebral hypoperfusion. It suggests that POL can be a beneficial medicinal herb to treat the brain diseases related to cerebral hypoperfusion.