• Journal of Korean Neurosurgical Society
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• v.40 no.3
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• pp.180-185
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• 2006

Objective : Middle cerebral artery occlusion[MCAO] has widely been used to produce ischemic brain lesions. The lesions induced by MCAO tend to be variable in size because of the variance in the collateral blood supply found in the mouse brain. To establish a less invasive and reproducible focal ischemia model in mice, we modified the technique used for rat photo thrombosis model. Methods : Male C57BL/6 mice were subjected to focal cerebral ischemia by photothrombosis of cortical microvessels. Cerebral infarction was produced by intraperitoneal injection of Rose Bengal, a photosensitive dye and by focal illumination through the skull. Motor impairment was assessed by the accelerating rotarod and staircase tests. The brain was perfusion-fixed for histological determination of infarct volume four weeks after stroke. Results : The lesion was located in the frontal and parietal cortex and the underlying white matter was partly affected. A relatively constant infarct volume was achieved one month after photothrombosis. The presence of the photothrombotic lesion was associated with severe impairment of the motor performance measured by the rotarod and staircase tests. Conclusion : Photothrombotic infarction in mice is highly reproducible in size and location. This procedure can provide a simple method to produce cerebral infarction in a unilateral motor cortex lesion. In addition, it can provide a suitable model for study of potential neuroprotective and therapeutic agents in human stroke.

• The Journal of Internal Korean Medicine
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• v.37 no.5
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• pp.733-740
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• 2016

Objective: To evaluate the effects of integrative treatment with conventional and Korean medicine on cerebral infarction due to presumed paradoxical embolism through a patent foramen ovale. Methods: We applied acupuncture, herbal medication, western medication, and physical therapy routinely every day and applied fluid therapy provided as needed. The NIHSS, K-MBI, MRS, MMT, and MMSE-K score were determined to assess any improvement in symptoms. Results: Scores appeared to be improved for the NIHSS (9 to 5), K-MBI (94 to 100), MRS (2 to 1), MMT (2+, 4 to 4, 4), MMSE-K (24 to 26). No side effects were observed during the treatment. Conclusions: This study demonstrates that integrative treatment with conventional and Korean medicine may be an effective option for treating cerebral infarction due to a presumed paradoxical embolism through a patent foramen ovale.

• Journal of Korean Neurosurgical Society
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• v.50 no.4
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• pp.370-376
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• 2011

Objective : Posttraumatic cerebral infarction (PTCI), an infarction in well-defined arterial distributions after head trauma, is a known complication in patients with severe head trauma. The primary aims of this study were to evaluate the clinical and radiographic characteristics of PTCI, and to assess the effect on outcome of decompressive hemicraniectomy (DHC) in patients with PTCI. Methods : We present a retrospective analysis of 20 patients with PTCI who were treated between January 2003 and August 2005. Twelve patients among them showed malignant PTCI, which is defined as PTCI including the territory of Middle Cerebral Artery (MCA). Medical records and radiologic imaging studies of patients were reviewed. Results : Infarction of posterior cerebral artery distribution was the most common site of PTCI. Fourteen patients underwent DHC an average of 16 hours after trauma. The overall mortality rate was 75%. Glasgow outcome scale (GOS) of survivors showed that one patient was remained in a persistent vegetative state, two patients were severely disabled and only two patients were moderately disabled at the time of discharge. Despite aggressive treatments, all patients with malignant PTCI had died. Malignant PTCI was the indicator of poor clinical outcome. Furthermore, Glasgow coma scale (GCS) at the admission was the most valuable prognostic factor. Significant correlation was observed between a GCS less than 5 on admission and high mortality (p<0.05). Conclusion : In patients who developed non-malignant PTCI and GCS higher than 5 after head injury, early DHC and duroplasty should be considered, before occurrence of irreversible ischemic brain damage. High mortality rate was observed in patients with malignant PTCI or PTCI with a GCS of 3-5 at the admission. A large prospective randomized controlled study will be required to justify for aggressive treatments including DHC and medical treatment in these patients.

• Progress in Medical Physics
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• v.21 no.4
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• pp.348-353
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• 2010

The purpose of this study was to explore the potentials of a clinical 3T MRI in mouse brains and technical adaptation and optimization. T1-weighted images (T1WI), T2-weighted images (T2WI), FLAIR (Fluid Attenuated Inversion Recovery) images, Gadolinium enhanced T1-weighted images (Gd-T1WI), Diffusion weighted images (DWI) were acquired in brain of 2 mice (weight 20~25 g) with cerebral infarction by occlusion of right middle cerebral artery, 1 hour, 24 hours, 72 hours after infarction and 1 normal mouse brain using clinical 3T MRI scanner. We analyzed differentiation of striatum, ventricle, cerebral cortex, and possibility of detection of acute cerebral infarction. We could differentiate the striatum, ventricle, cerebral cortex on T2WI and on DWI, FLAIR, T1WI, the differentiation of each anatomy of brain was not definite, but acute cerebral infarction was detected on DWI of 1 hour, 24 hours, 72 hours after infarction and on T2WI, FLAIR of 24 hours, 72 hours after infarction. Clinical 3T MRI can be used in differentiation of anatomy of mouse brains and DWI can be helpul in detection of acute cerebral infarction in acute phase. With technical adaptation and optimization clinical 3T MRI can be useful tool for provide preclinical and clinical small animal studies.

• Journal of Acupuncture Research
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• v.27 no.4
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• pp.29-38
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• 2010

Objectives : The purpose of the study is to determine the neuroprotective effect of modified Boyanghwano-tang(mBHT), a traditional Korean medicine, on the transient focal cerebral ischemia in rats. Methods : Focal ischemia and reperfusion were induced by middle cerebral artery occlusion(MCAO) for 90 min, followed by 144 h reperfusion in rats. mBHT(200mg/kg body weight, p.o.) was administrated in rats once a day during reperfusion. At the end of treatment, brain infarction was measured by TTC staining, and histological change was observed by H&E staining. The expressions of Bax, Bcl-2 and cytochrome c in ischemic brains were determined by immunofluorescent analysis. Results : mBHT significantly reduced the cerebral infarct volumes of the MCAO rats. mBHT also attenuated the neuronal cell death and the expressions of pro-apoptotic molecules, bax and cytochrome c in ischemic brains. Further, mBHT significantly increased the survival time of ischemeic rats and the expression of anti-apoptotic molecule, Bcl-2 in ischemic brains. Conclusions : Our results suggest that mBHT is neuroprotective and may prove to be useful adjunct in the treatment of ischemic stroke.

• Biomolecules & Therapeutics
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• v.32 no.3
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• pp.319-328
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• 2024

Lysophosphatidic acid receptor 1 (LPA₁) plays a critical role in brain injury following a transient brain ischemic stroke. However, its role in permanent brain ischemic stroke remains unknown. To address this, we investigated whether LPA₁ could contribute to brain injury of mice challenged by permanent middle cerebral artery occlusion (pMCAO). A selective LPA₁ antagonist (AM152) was used as a pharmacological tool for this investigation. When AM152 was given to pMCAO-challenged mice one hour after occlusion, pMCAO-induced brain damage such as brain infarction, functional neurological deficits, apoptosis, and blood-brain barrier disruption was significantly attenuated. Histological analyses demonstrated that AM152 administration attenuated microglial activation and proliferation in injured brain after pMCAO challenge. AM152 administration also attenuated abnormal neuroinflammatory responses by decreasing expression levels of pro-inflammatory cytokines while increasing expression levels of anti-inflammatory cytokines in the injured brain. As underlying effector pathways, NF-κB, MAPKs (ERK1/2, p38, and JNKs), and PI3K/Akt were found to be involved in LPA₁-dependent pathogenesis. Collectively, these results demonstrate that LPA₁ can contribute to brain injury by permanent ischemic stroke, along with relevant pathogenic events in an injured brain.

• Biomedical Science Letters
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• v.11 no.3
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• pp.307-310
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• 2005

Cerebral ischemia results in neuronal changes in remote areas that have fiber connections with the ischemic area. The aim of this study was to investigate the nigral changes by examining the correlation between the apparent diffusion coefficient (ADC) and the tissue structure. Sprague-Dawley rats were subjected to middle cerebral artery occlusion. Four days after the occlusion, when T2-weighted images revealed the presence of an area of high signal intensity in the ipsilateral substantia nigra, and the ADCs were calculated and imaged. Histopathologic examination by both light and electron microscopy was performed on day 4 after surgery. This finding was consistent with the high signal intensity seen on T2-weighted and diffusion-weighted images, as well as with the ADC reduction, but we did not expect to observe uniform ADC reduction attributable mainly to astrocytic swelling in the perivascular end-feet.

• Journal of Korean Neurosurgical Society
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• v.41 no.1
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• pp.30-38
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• 2007

Objective : To elucidate the role of aquaporin-4[AQP4] in cerebral edema formation, we studied the expression and subcellular localization of AQP4 in astrocytes after focal cerebral ischemia. Methods : Cerebral ischemia were induced by permanent middle cerebral artery[MCA] occlusion in rats and estimated by the discoloration after triphenyltetrazolium chloride[TTC] immersion. Change of AQP4 expression were evaluated using western blot. Localization of AQP4 was assessed by confocal microscopy and its interaction with ${\alpha}-syntrophin$ was analyzed by immunoprecipitation. Results : After right MCA occlusion, the size of infarct and number of apoptotic cells increased with time. The ratio of GluR1/GluR2 expression also increased during ischemia. The polarized localization of AQP4 in the endfeet of astrocytes contacting with ventricles, vessels and pia mater was changed into the diffuse distribution in cytoplasm. The interactions of AQP4 and Kir with ${\alpha}-syntrophin$, an adaptor of dystrophin complex, were disrupted by cerebral ischemia. Conclusion : The deranged spatial buffering function of astrocytes due to mislocalized AQP4/Kir4.1 channel as well as increased assembly of $Ca^{2+}$ permeable AMPA receptors might contribute to the development of edema formation and the excitotoxic neuronal cell death during ischemia.

• The Journal of Internal Korean Medicine
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• v.22 no.3
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• pp.341-351
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• 2001

Object: Acori graminei rhizoma(AGR) extract is clinically used to treat the cerebral ischemia in Korea. The present study was undertaken to study the neuroprotective effect of AGR extract in middle cerebral artery occlusion(MCAO) rats. Methods: Changes of extracellular levels of glutamate, aspartate, GABA, glycine, taurine, tyrosine, alanine in striatum were collected at 20 minutes interval by in vivo microdialysis and then analyzed by HPLC(high performance liquid chromatography) in rats subjected to permanent focal cerebral ischemia induced by 2 hours of MCAO. AGR extract was orally administrated before MCAO. Different animals were used for measurement of cerebral infarction volume induced by 24 hours of MCAO with TTC staining and image analysis. Result : The infarction volume was decreased and focal cerebral ischemia - induced increase of extracellular glutamate, aspartate, and tyrosine were inhibited after the treatment of AGR extract. On the other hand, the increase of glycine and alanine not but GABA and taurine were enhenced after the treatment of AGR extract. Conclusion: These results suggest that AGR extract can playa role in protecting against cerebral ischemia by regulating extracellular levels of excitatory and inhibitory amino acid neurotransmitters.

• The Korea Journal of Herbology
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• v.27 no.2
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• pp.61-67
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• 2012

Objective : Angelica Gigas Nakai is a popular oriental medicine used for the treatment of vascular diseases. The aim of this study is to investigate neuroprotective effect of the water extract of Anelicae Gigantis Radix Palva (AG) in transient middle cerebral artery occlusion (tMCAO)-induced ischemic rats via the regulation of angiogenesis-related molecules. Methods : Sprague-Dawley rats were intraperitoneally administrated with AG water extract at doses of 10, 25, 50 mg/kg body weight after tMCAO (90 min occlusion). reperfusion for 24 hr infarction volumes were measured by 2,3,5-tetrazolium chloride (TTC) staining. Brain tissues were observed neuronal cell injuries by nissl staining, and also brain-blood barrier (BBB) permeability change by evans blue. Expression of vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1) and Tie-2 receptor protein in brain tissues was determined by western blot. Results : AG water extract significantly reduced infarction volume in ischemic brains of rats, degradation of neuronal cell, BBB permeability and expression of VEGF protein dose-dependently. Ang-1 protein was increased dose-dependantly, not significantly. Conclusion : This study suggests that AG water extract shows neuroprotective effect by preventing BBB breakdown, with regulating angiogenesis factor VEGF and Ang-1.