• Journal of Korean Neurosurgical Society
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• v.64 no.5
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• pp.693-704
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• 2021

Objective : Endovascular mechanical thrombectomy (MT) has been regarded as one of the standard treatments for acute ischemic stroke caused by large vessel occlusion. Despite the wide use of stent retrievers for MT, arterial intimal damage caused when deployed stent is pulled has been a certain disadvantage. We hypothesized that statin could protect and stabilize vessel damage after endovascular MT using a stent retriever. In this animal study, we observed the protective effects of the statins towards MT-induced vessel wall injury. Methods : Twenty-eight carotid arteries of fourteen rabbits were used in the experiments with MT using stent retriever. We divided the rabbits into four groups as follows : group 1, negative control; group 2, positive control; group 3, statin before MT; and group 4, statin after MT. After MT procedures, we harvested the carotid arteries and performed histomorphological and immunohistochemical analyses. Results : In histomorphological analysis with hematoxylin and eosin and Masson's trichrome stain, significant intimal thickening (p<0.05) was observed in the positive control (group 2), compared to in the negative control (group 1). Intimal thickening was improved in the statin-administered groups (groups 3 and 4 vs. group 2, p<0.05). We also observed that statin administration after MT (group 4) resulted in a more effective decrease in intimal thickness than statin administration before MT (group 3) (p<0.05). We performed immunohistochemical analysis with the antibodies for tumor necrosis factor-alpha (TNF-α), cluster of differentiation (CD)11b, and CD163. In contrast to the negative control (group 1), the stained percentage areas of all immunological markers were markedly increased in the positive control (group 2) (p<0.05). Based on statin administration, the percentage area of TNF-α staining was significantly reduced (p<0.05) in group 3, compared to the positive control group (group 2). However, significant differences were not observed for CD11b and CD163 staining. In group 4, no significant differences were observed for TNF-α, CD11b, and CD163 staining (p≥0.05). The differences in the percentage areas of the different markers between the statin-administered groups (groups 3 and 4) were also not revealed. Conclusion : We presented that statin administration before and after MT exerted protective effects towards vessel wall injury. The efficacy of statins was greater post-administration than pre-administration. Thus, statin administration in routine prescriptions in the peri-procedural period is strongly advised.

• Biomolecules & Therapeutics
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• v.8 no.2
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• pp.160-166
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• 2000

The present study examined influence of various ischemic duration on extent of focal ischemic brain injury induced by middle cerebral artery occlusion (MCAO) in rats. The MCAO was produced by insertion of a 17 mm silicone-coated 4-0 nylon surgical thread to the origin of MCA through the internal carotid artery for 30, 60, 90, 120 min (transient) or 24 hr (permanent) in male Sprague-Dawley rats under isoflurane anesthesia. Reperfusion in transient MCAO models was achieved by pulling the thread out of the internal carotid artery. Only rats showing neurological deficits characterized by left hemiparesis and/or circling to the left, were included in cerebral ischemic groups. The rats were sacrificed 24 hr after MCAO and seven serial coronal slices of the brain were stained with 2,3,5-triphenyltetrazolium chloride. Infarct size was measured using a computerized image analyzer. Ischemic damage was common in the frontoparietal cortex (somatosensory area) and the lateral segment of the striatum while damage to the medial segment of the striatum depended on the duration of the occlusion. In the 30-min MCAO grouts, however, infarcted region was primarily confined to the striatum and it was difficult to clearly delineate the region since there was mixed population of live and dead cells in the nucleus. Infarct volume was generally increased depending on the duration of MCAO, showing the most severe damage in the permanent MCAO group. However, there was no significant difference in infarct size between the 90-min and 120-min MCAO groups. % Edema also tended to increase depending on the duration of MCAO. The results suggest that the various focal ischemic rat models established in the present study can be used to evaluate in vivo neuroprotective activities of candidate compounds or to elucidate pathophysiological mechanisms of ischemic neuronal cell death.

• Natural Product Sciences
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• v.26 no.1
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• pp.71-78
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• 2020

The plant Dendropanax morbifera Léveille is effective folk medicines for the treatment of several conditions, such as infectious diseases, skin diseases, and other illnesses. Although the inhibitory effects of D. morbifera on the proliferation and migration of vascular smooth muscle cells (VSMCs) have been shown in our previous study, its effects in vivo remain to be elucidated. In this study, we aimed to investigate the protective effects of the extracts from D. morbifera (EDM) on neointimal hyperplasia of rat carotid artery and explore the underlying mechanisms. We observed that the ratio of intima to media thickness (I/M) was significantly decreased in the EDM-treated groups by ~80% compared to that of the control. The expression of Ki-67 and proliferating cell nuclear antigen was decreased by ~70% in the EDM-treated groups compared to that of the control. In addition, matrix metalloproteinase (MMP)2 and MMP9 significantly reduced in the neointimal layer of the EDM-treated groups. Moreover, the decreased levels of contractile phenotypic markers of VSMCs, such as α-smooth muscle actin, myocardin, and smooth muscle-myosin heavy chain, were successfully restored by EDM treatment. Furthermore, the levels of synthetic phenotypic markers, cellular retinal binding protein 1 and connexin 43 were also restored to normal levels. These results suggest that EDM inhibits vascular neointimal hyperplasia induced by balloon injury in rats via phenotypic modulation of VSMCs. Therefore, EDM may be a potential drug candidate for the prevention of restenosis.

• Preventive Nutrition and Food Science
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• v.19 no.3
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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.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.6
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• pp.485-491
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• 2013

The present study was designed to investigate the putative effect of neurosteroid modulation on global ischaemia-reperfusion-induced cerebral injury in mice. Bilateral carotid artery occlusion followed by reperfusion, produced a significant rise in cerebral infarct size along with impairment of grip strength and motor coordination in Swiss albino mice. Administration of carbamazepine (16 mg/kg, i.p.) before global cerebral ischaemia significantly attenuated cerebral infarct size and improved the motor performance. However, administration of indomethacin (100 mg/kg, i.p.) attenuated the neuroprotective effect of carbamazepine. Mexiletine (50 mg/kg, i.p.) did not produce significant neuroprotective effect. It may be concluded that the neuroprotective effect of carbamazepine may be due to increase in synthesis of neurosteroids perhaps by activating enzyme ($3{\alpha}$ HSD) as indomethacin attenuated the neuroprotective effect of carbamazepine. The sodium channel blocking effect of carbamazepine may not be involved in neuroprotection as mexiletine, a sodium channel blocker, did not produce significant neuroprotective effect.

• Journal of Society of Preventive Korean Medicine
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• v.12 no.3
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• pp.67-80
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• 2008

The pathobiologic process of arterial stenosis following balloon angioplasty continues to be an enigmatic problem in clinical settings. This study investigates the ability of demethoxycurcumin, a curcuminoid isolated from Radix Curcumae, to attenuate balloon injury-induced neointima(NI) formation in the rat carotid artery. It was found that demethoxycurcumin induced inducible heme oxygenase(HO-1) expression and inhibited dose-dependently cellular proliferation in rat vascular smooth muscle cells. Perivascular application of demethoxycurcumin immediately following injury significantly reduced NI area and NI thickness 2 weeks post-injury. Interestingly, treatment with tin-protoporphyrin IX, a HO inhibitor, reversed the effects of demethoxycurcumin on NI formation. These results implicate demethoxycurcumin as a potent new therapeutic agent that is capable of reducing post-angioplasty arterial stenosis through induction of the HO-1 expression.

• Korean Journal of Plant Resources
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• v.26 no.6
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• pp.678-685
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• 2013

The objective of this study was to examine the effect of 7 traditional Korean formulations (7TKFs) on intimal thickening of rat carotid artery injured by balloon catheter in vivo and on the proliferation of human smooth muscle cells (HASMCs) and secretion of matrix metalloproteinase-2 (MMP-2) in vitro. 7TKFs (400 mg/kg) were administered orally for 4 weeks from the day of balloon injury in the rats. HASMC proliferation was assessed by 3-(4,5-dimethylthiazol-2)-2,5-diphenyltetrazolium bromide (MTT) assay while enzymatic action of MMP-2 was carried out by gelatin zymography. Among 7TKFs, Samhwang-sasim-tang (SST), Banha-sasim-tang (BST) and Kegi-honghwa-tang (KHT) significantly reduced the intimal thickening by suppressing HASMC proliferation and MMP-2 expression in both extracellular and intracellular levels. Thus, the results suggest that SST, BST and KHT can be considered as a therapeutic value in the prevention of atherosclerosis because restenosis after PTCA (percutaneous transluminal coronary angioplasty) is supposed to be 'accelerated atherosclerosis'.

• Biomedical Science Letters
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• v.10 no.2
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• pp.115-120
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• 2004

To investigate the correlation between the magnetic resonance imaging (MRI) of cerebral fat embolism that is induced by injecting oleic acid into 10 cats, and a pathologic diagnosis. Using a microcatheter, 30 ${mu}ell$ of oleic acid was injected into the internal carotid artery of 10 cats. MR T2-weighted image (T2WI), diffusion-weighted image (DWI) and Gadolinium-enhanced T1-weighted image (Gd-enhanced T1WI) were obtained after 30 minutes and 2 hours of embolization. After 30 minutes of the embolization, lesions of very high signal intensity were detected by T2WI in 6 cats, and of slightly high signal intensity in 2 cats; in the remaining 2 cats, signal intensity was normal. DWI showed lesions of very high intensity in 9 cats and of slightly high intensity in one cat. According to the findings of light microscopic examination, infarcted lesions mainly involved the gray matter, but also some white matter. A magnetic resonance imaging diagnosis for cerebral fat embolism that was induced by oleic acid through the internal carotid artery in cats showed high signal intensity on the T2WI and the DWI within an initial 2 hours, and with a well enhancement on the Gd-enhanced T1WI. Considering cellular edema, cerebrovascular injury and extracellular space widening, we assumed pathologically that cytotoxic and vasogenic edema exists at the same time.

• Journal of Korean Neurosurgical Society
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• v.40 no.6
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• pp.455-458
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• 2006

The incidence of blindness after aneurysm surgery is very rare. We experienced a case of unilateral blindness after internal carotid artery[ICA] aneurysm wrapping. A 43-year-old male immediately developed ipsilateral ocular pain and visual loss in his left eye after the treatment of a lateral ICA aneurysm by wrapping with muscle pieces. He had also multiple aneurysms, which were multilobulated anterior communicating artery [A-com], middle cerebral artery[MCA] and posterior communicating artery [P-com] aneurysms. Coilings were done for a part of A-com artery aneurysm and P-com artery aneurysm on admission. The remaining A-com artery aneurysm was clipped and ICA aneurysm was wrapped with temporal muscle piece. A retrobulbar optic neuropathy might have resulted from either direct injury or damage to small dural vessels of the posterior optic nerve. Actually, the optico-carotid space was tight and the optic nerve was compressed by swollen muscle piece. Despite releasing of compression of the optic nerve on second day, his visual loss was irreversible.

• Journal of Korean Neurosurgical Society
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• v.49 no.5
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• pp.287-289
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• 2011

Thalamoperforating artery aneurysms are rarely reported in the literature. We report an extremely rare case of ruptured distal anterior thalamoperforating artery aneurysm which was treated by endovascular obliteration in a patient with occlusion of both the internal carotid arteries (ICAs) : A 72-year-old woman presented with severe headache and loss of consciousness. Initial level of consciousness at the time of admission was drowsy and the Glasgow Coma Scale score was 14. Brain computed tomography (CT) scan was performed which revealed intracerebral hemorrhage in right basal ganglia, subarachnoid hemorrhage, and intraventricular hemorrhage. The location of the aneurysm was identified as within the globus pallidus on CT angiogram. Conventional cerebral angiogram demonstrated occlusion of both the ICAs just distal to the fetal type of posterior communicating artery and the aneurysm was arising from right anterior thalamoperforating artery (ATPA). A microcatheter was navigated into ATPA and the ATPA proximal to aneurysm was embolized with 20% glue. Post-procedural ICA angiogram demonstrated no contrast filling of the aneurysm sac. The patient was discharged without any neurologic deficit. Endovascular treatment of ATPA aneurysm is probably a more feasible and safe treatment modality than surgical clipping because of the deep seated location of aneurysm and the possibility of brain retraction injury during surgical operation.