• The Korean Journal of Physiology and Pharmacology
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• 제9권6호
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• pp.327-332
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• 2005

The preventive effects of gene transfer of human copper/zinc superoxide dismutase (Cu/ZnSOD) on the development of cerebral vasospasm after subarachnoid hemorrhage (SAH) were examined usin a rat model of SAH. An experimental SAH was produced by injecting autologous arterial blood twice into the cisterna magna, and the changes in the diameter of the middle cerebral artery (MCA) were measured. Rats subjected to SAH exhibited a decreased diameter with an increased wall thickness of MCA that were significantly ameliorated by pretreatment with diphenyleneiodonium (DPI, $10{\mu}M$), an inhibitor of NAD(P)H oxidase. Furthermore, application of recombinant adenovirus ($100{\mu}l$ of $1{\times}10^{10}$ pfu/ml, intracisternally), which encodes human Cu/ZnSOD, 3 days before SAH prevented the development of SAH-induced vasospasm. Our findings demonstrate that SAH-induced cerebral vasospasm is closely related with NAD(P)H oxidase-derived reactive oxygen species, and these alterations can be prevented by the recombinant adenovirus-mediated transfer of human Cu/ZnSOD gene to the cerebral vasculature.

• 한국식생활문화학회지
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• 제25권2호
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• pp.232-239
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• 2010

This study was designed to investigate the effects of green tea extract on aluminum-induced damage to phospholipid content in old rat cerebral tissue. The aim of this study was to investigate the possibility that aluminum is the cause of Alzheimer's disease. Forty Sprague-Dawley old male rats weighing 350$\pm$10 g were divided into four groups, consisting of a control group (CON), 40 ppm aluminum sulfate group (Al-40), green tea water extract group (GTWE), and 40 ppm aluminum sulfate and green tea water extract groups (Al-40+GTWE) and kept on their respective diets for 12 weeks. In order to discover the influence of aluminum on cerebral tissue of old male rats, the serum aluminum concentration and phospholipid composition were compared between the aluminum-treated group and the normal group. The results showed that the serum aluminum concentration was higher in the aluminum sulfate-treated group than in the normal group. The cerebral tissue phospholipid concentration decreased significantly in the aluminum sulfate treated group as compared to the normal group. The results of this experiment show that increase of aluminum concentration in experimental animals causes the rise of serum aluminum and phospholipid concentrations, phenomena that are very similar to those shown in Alzheimer's disease., The results of this experiment, together with reports that aluminum is a cause of neurofibrillary tangles in cerebral tissue, therefore demonstrate the possibility that aluminum is the cause of Alzheimer's disease. Green tea water extract is also shown to be an effective therapeutic candidate for the treatment of Alzheimer's disease.

• Journal of Korean Neurosurgical Society
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• 제40권4호
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• pp.267-272
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• 2006

Objective : There have been recent reports that mesenchymal stromal cells that are harvested from adipose tissue are able to differentiate into neurons. In the present study, we administered adipose tissue derived stem cells in rats with cerebral infarction in order to determine whether those stem cells could enhance the recovery of motor function. Methods : Cerebral infarction was induced by intraluminal occlusion of middle cerebral artery in rats. The adipose tissue-derived mesenchymal stem cells were harvested from inguinal fat pad and proliferated for 2 weeks in DMEM media. Approximately $1{\times}10^6$ cells were injected intravenously or into subdural space of the peri-lesional area. The rotor rod test was performed at preoperative state[before MCA occlusion], and 1, 2, 3, 4, 6, 8 and 10 weeks after the cell therapy. Results : The motor functions that were assessed by rotor rod test at 1 week of the cell therapy were nearly zero among the experimental groups. However, there was apparent motor function recovery after 2 weeks and 4 weeks of cell injection in intravenously treated rats and peri-lesionaly treated rats, respectively, while there was no significant improvement till 8 weeks in vehicle treated rats. Conclusion : These results demonstrate that the adipose derived stem cell treatment improves motor function recovery in rats with cerebral infarction.

• The Korean Journal of Physiology and Pharmacology
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• 제13권3호
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• pp.257-263
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• 2009

This study aimed to investigate whether selective serotonin reuptake inhibitors (SSRIs) attenuate brain injury and facilitate recovery following photothrombotic cortical ischemia in mice. Male ICR mice were anesthetized and systemically administered Rose Bengal. Permanent focal ischemia was induced in the medial frontal and somatosensory cortices by irradiating the skull with cold light laser. The animals were treated with fluoxetine or sertraline once a day for 14 d starting 1 h after ischemic insult. Treatment with fluoxetine and sertraline significantly reduced the infarct size. The Evans blue extravasation indices of the fluoxetine- and sertraline-treated groups were significantly lower than that of the vehicle group. Treatment with fluoxetine and sertraline shifted the lower limit of the mean arterial blood pressure for cerebral blood flow autoregulation toward normal, and significantly increased the expression of heme oxygenase-1 (HO-1) and hypoxia-inducible factor-1 ${\alpha}$ (HIF-1 ${\alpha}$) proteins in the ischemic region. These results suggest that SSRIs, such as fluoxetine and sertraline, facilitate recovery following photothrombotic cortical ischemia via enhancement of HO-1 and HIF-1 ${\alpha}$ proteins expression, thereby providing a benefit in therapy of cerebral ischemia.

• Laboraroty Animal Research
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• 제33권3호
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• pp.244-250
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• 2017

${\alpha}$-Synuclein is abundantly expressed in neuronal tissue, plays an essential role in the pathogenesis of neurodegenerative disorders, and exerts a neuroprotective effect against oxidative stress. Cerebral ischemia causes severe neurological disorders and neuronal dysfunction. In this study, we examined ${\alpha}$-synuclein expression in middle cerebral artery occlusion (MCAO)-induced cerebral ischemic injury and neuronal cells damaged by glutamate treatment. MCAO surgical operation was performed on male Sprague-Dawley rats, and brain samples were isolated 24 hours after MCAO. We confirmed neurological behavior deficit, infarction area, and histopathological changes following MCAO injury. A proteomic approach and Western blot analysis demonstrated a decrease in ${\alpha}$-synuclein in the cerebral cortices after MCAO injury. Moreover, glutamate treatment induced neuronal cell death and decreased ${\alpha}$-synuclein expression in a hippocampal-derived cell line in a dose-dependent manner. It is known that ${\alpha}$-synuclein regulates neuronal survival, and low levels of ${\alpha}$-synuclein expression result in cytotoxicity. Thus, these results suggest that cerebral ischemic injury leads to a reduction in ${\alpha}$-synuclein and consequently causes serious brain damage.

• The Korean Journal of Physiology and Pharmacology
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• 제15권2호
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• pp.115-122
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• 2011

The aim of this study was to investigate whether matrix metalloproteinase (MMP) inhibitors attenuate neuroinflammation in an ischemic brain following photothrombotic cortical ischemia in mice. Male C57BL/6 mice were anesthetized, and Rose Bengal was systemically administered. Permanent focal ischemia was induced in the medial frontal and somatosensory cortices by irradiating the skull with cold white light. MMP inhibitors, such as doxycycline, minocycline, and batimastat, significantly reduced the cerebral infarct size, and the expressions of monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and indoleamine 2,3-dioxygenase (IDO). However, they had no effect on the expressions of heme oxygenase-1 and neuroglobin in the ischemic cortex. These results suggest that MMP inhibitors attenuate ischemic brain injury by decreasing the expression levels of MCP-1, TNF-${\alpha}$, and IDO, thereby providing a therapeutic benefit against cerebral ischemia.

• 대한핵의학회지
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• 제35권6호
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• pp.343-351
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• 2001

Cerebral post-ischemic hyperperfusion has been observed at the acute and subacute periods of ischemic stroke. In the animal stroke model, early post-ischemic hyperperfusion is the mark of recanalization of the occluded artery with reperfusion. In the PET studios of both humans and experimental animals, early post-ischemic hyperperfusion is not a key factor in the development of tissue infarction and indicates the spontaneous reperfusion of the ischemic brain tissue without late infarction or with small infarction. But late post-ischemic hyperperfusion shows the worse prognosis with reperfusion injury associated with brain tissue necrosis. Early post-ischemic hyperperfusion defined by PET and SPECT may be useful in predicting the prognosis of ischemic stroke and the effect of thrombolytic therapy.

• 턱관절균형의학회지
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• 제9권1호
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• pp.4-11
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• 2019

Objectives: Although intraoral balancing appliance therapy has been used effective to several diseases, verification studies through cerebral diseases are poorly reported so far. Thus we investigated the effect of tooth-cut induced dental malocclusion against mouse model of ischemic stroke. Methods: Tooth-cut and 90 min middle cerebral artery occlusion (MCAO) were loaded to C57BL/6 male mice, and total infarct area, neurological deficit scores (NDS), histological change of hippocampal region were observed. Production levels of reactive oxygen species (ROS) and inducible nitric oxide synthase (iNOS) in cerebral tissue were also measured. Results: The longer the tooth-cut period, the greater the area of cerebral infarction caused by MCAO, and NDS began to increase as the tooth was cut, and the results were more negative when MCAO was loaded. Histological change of hippocampal cells was significant when tooth-cut was maintained for 7 days. Those damages were thought to depend on the generation of ROS and iNOS in brain tissue. Conclusions: Since tooth-cut increased total area of cerebral infarction due to MCAO in mice, it is able to be confirmed that anomaly of the temporomandibular occlusion can affect neurological diseases.

• International Journal of Stem Cells
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• 제15권1호
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• pp.95-103
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• 2022

Background and Objectives: In recent years, brain organoid technologies have been the most innovative advance in neural differentiation research. In line with this, we optimized a method to establish cerebral organoids from feeder-free cultured human pluripotent stem cells. In this study, we focused on the consistent and robust production of cerebral organoids comprising neural progenitor cells and neurons. We propose an optimal protocol for cerebral organoid generation that is applicable to both human embryonic stem cells and human induced pluripotent stem cells. Methods and Results: We investigated formation of neuroepithelium, neural tube, and neural folding by observing the morphology of embryoid bodies at each stage during the cerebral organoid differentiation process. Furthermore, we characterized the cerebral organoids via immunocytochemical staining of sectioned organoid samples, which were prepared using a Cryostat and Vibratome. Finally, we established a routine method to generate early cerebral organoids comprising a cortical layer and a neural progenitor zone. Conclusions: We developed an optimized methodology for the generation of cerebral organoids using hESCs and hiPSCs. Using this protocol, consistent and efficient cerebral organoids could be obtained from hiPSCs as well as hESCs. Further, the morphology of brain organoids could be analyzed through 2D monitoring via immunostaining and tissue sectioning, or through 3D monitoring by whole tissue staining after clarification.

• Journal of Korean Neurosurgical Society
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• 제30권9호
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• pp.1072-1078
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• 2001

Objectives : There is continuing controversy about the benefits of decompressive craniectomy in massive cerebral edema following space occupying hemispheric cerebral infarction. The aims of this study are to determine the effectiveness and to confirm the life-saving nature of decompressive craniectomy with dural augmentation for massive cerebral infarction. Patients and Methods : We present twelve patients with medically uncontrollable hemispheric cerebral infarction. All were treated with extensive craniectomy and duroplasty without resection of necrotic tissue. We evaluated various characteristics(size of hemispheric infarction, Glasgow Coma Scale, volume of low density and midline shift in CT) at three different periods(preoperative, immediate postoperative and 3-4weeks after operation) and evaluated effectiveness of hemicraniectomy for massive cerebral edema after large hemispheric infarction. Results : All patients have survived from surgery. Nine patients with nondominant hemispheric infarction showed significant functional recovery with minimal assistance, and remaining two patients with dominant hemispheric infarction and one patient with nondominant hemispheric infarction have functionally dependent. The volume of low density and midline shift in CT were significantly reduced after decompressive craniectomy. Conclusions : Our results indicate that decompressive craniectomy with dural augmentation without resection of necrotic tissue for massive cerebral hemispheric infarction not only reduce the mortality and infarction size but also significantly improve the outcome, especially for nondominant hemispheric infarction.