• The Journal of Internal Korean Medicine
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• v.30 no.4
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• pp.674-684
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• 2009

Objectives : In conditions of brain infarction, irreversible axon damage occurs in the central nerve system (CNS), because gliosis becomes a physical and a mechanical barrier to axonal regeneration. Reactive gliosis induced by ischemic injury such as middle cerebral artery occlusion is involved with up-regulation of GFAP and CD81. This study was undertaken to examine the effect of the Gongjin-dan (GJD) on CD81 and GFAP expression and its pathway in the rat brain following middle cerebral artery occlusion (MCAO). Methods : In order to study ischemic injuries on the brain, infarction was induced by MCAO using insertion of a single nylon thread, through the internal carotid artery, into a middle cerebral artery. Cresyl violet staining, cerebral infarction size measurement, immunohistochemistry and microscopic examination were used to detect the expression of CD81 and GFAP and the effect on the infarct size and pyramidal cell death in the brain of the rat with cerebral infarction induced by MCAO. Also, c-Fos and ERK expression were measured to investigate the signaling pathway after GJD administration in MCAO rats. Results : Measuring the size of cerebral infarction induced by MCAO in the rat after injection of GJD showed the size had decreased. GJD administration showed pyramidal cell death protection in the hippocampus in the MCAO rat. GJD administration decreased GF AP expression in the MCAO rat. GJD administration decreased CD81 expression in the MCAO rat. GJD administration induced up-regulation of c-FOS expression compared with MCAO. GJD administration induced down-regulation of ERK expression compared with MCAO. Conclusion : We observed that GJD could suppress the reactive gliosis, which disturbs the axonal regeneration in the brain of a rat with cerebral infarction after MCAO by controlling the expression of CD81 and GFAP. The effect may be modulated by the regulation of c-Fos and ERK. These results suggest that GJD can be a candidate to regenerate CNS injury.

• Journal of Acupuncture Research
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• v.36 no.4
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• pp.220-229
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• 2019

Background: The therapeutic potential of Bee Venom Pharmacopuncture (BVP) on acute ischemic cerebral infraction was determined in mice in vivo and in vitro. Methods: Analysis of acute ischemic cerebral infraction was performed using 7 week old male ICR mice (n = 20) and microglial BV-2 cells. Bee venom ($5{\mu}g/kg$) was injected into the caudal vein of middle cerebral artery occlusion (MCAo) mice (1 hour after reperfusion, 3 hours after MCAo probe insertion), and also used to treat LPS-stimulated microglial BV-2 cells (1, 2, $5{\mu}g/mL$). Markers of inflammation were monitored. Results: NO declined statistically significantly in BVP treated MCAo mice compared to the untreated MCAo group (p < 0.05). Compared to the MCAo group, the BVP-treated MCAo group showed a decreased production volume of malondialdehyde, but an increased glutathione/oxidized glutathione ratio. Compared to the untreated MCAo group, the BVP treated MCAo group showed a statistically significant decline in TNF and $IL-1{\beta}$ levels (p < 0.05). BVP inhibited the levels of p65, p50, $p-I{\kappa}B-{\alpha}$, and levels of p-ERK1/2, p-JNK2, p-P38 declined. Conclusion: BVP is effective at dampening the inflammatory response in vivo and in vitro and may supplement rt-PA treatment.

• Journal of Korean Neurosurgical Society
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• v.42 no.5
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• pp.413-415
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• 2007

A 26-year-old man was admitted to our department due to intermittent left hemiparesis for 3 months. Magnetic resonance Image showed subacute infarction in the right precentral gyrus. Digital subtraction angiography and magnetic resonance angiography revealed an aneurysmal protrusion at the right middle cerebral artery (MCA) bifurcation. It was difficult to differentiate the aneurysm from the occlusion of the middle trunk of the MCA trifurcation. Brain single photon emission computerized tomography showed a decrease in perfusion in the right posterior frontal lobe without vascular reserve. Therefore, we planned a superficial temporal artery MCA anastomosis with an exploration of the right MCA bifurcation. Intraoperatively, the aneurysmal opacification on preoperative angiography proved to be the proximal stump of the occluded middle trunk of the MCA trifurcation. An aneurysmal protrusion at the MCA bifurcation does not always indicate an aneurysm. In diagnosing protruding vascular lesions at the MCA bifurcation, the possibility of a vascular stump should be considered according to their angioanatomical appearance and the history of the patient.

• The Journal of Korean Medicine
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• v.21 no.2
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• pp.68-78
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• 2000

Objective : This research was performed to investigate protective effects of Sophora subprostrata, against ischemic brain damage after a middle cerebral artery(MCA) occlusion. The effect was estimated using histological test, neurobehavioural test, and biochemical test. Methods : Rats(Sprague-Dawley) were divided into four groups: Sham operated group, MCA occluded group, Sophora subprostrata administrated group after MCA occlusion, and Normal group. The MCA was occluded by intraluminal method. Sophora subprostrata was administrated orally twice(l and 4 hours) after middle cerebral artery occlusion. The neurobeavioural test was performed at 3 hours, 6 hours, 9 hours and 24 hours after the surgery by posture reflex test and swimming behavioural test. All groups were sacrificed at 24 hours after the surgery. The brain tissue was stained with 2% triphenyl tetrazolium chioride(TTC) or 1 % cresyl violet solution, to examine effect of Sophora subprostrata on ischemic brain tissue. The blood samples were obtained from the heart of rats. Tumor necrosis factor-a level was measured from sera using Enzyme-Linked Immunoabsorbent Assay(ELISA). Results : The results showed that (1) Sophora subprostrata reduced infarct size and total infarct volume by 54.8% compared to the control group, (2) that neuronal death, which was shown by decrease in cell number and size, was attenuated significantly in the boundary area of the infarction, (3) that serum $TNF-{\alpha}$ㆍlevel was reduced significantly, and finally, there was significant recovery of motor deficit at 3 hours after MCA occluded by Swimming behavioural test. Conclusions :In conclusion, Sophora subprostrata has protective effects against ischemic brain damage at the early stage of ischemia.

• Journal of Veterinary Clinics
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• v.33 no.1
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• pp.10-15
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• 2016

The purpose of this study was to establish reproducible ischemic infarction model using allogenic blood clot in beagle dogs and identify induced ischemic lesion after middle cerebral artery occlusion using magnetic resonance imaging (MRI) and histopathologic findings. Twenty eight male beagle dogs with no evidence of neurologic disease were experimented. Allogenic embolus was made using a healthy beagle dog. After internal carotid artery (ICA) was exposure, 16G catheter was introduced through the ICA. The dog was administered 0.3 ml blood clot for 15 seconds followed by 3 ml of saline for 15 seconds. MRI scans were performed with 1.5T to evaluate ischemic lesion at 7 days after middle cerebral artery occlusion procedure. Evaluation parameters of MRI include location, distribution, infarction type, margin, shape, mass effect and intensity of T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), fluid attenuated inversion recovery (FLAIR) sequence, diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC). On MRI, all dogs (28/28) showed focal or multifocal lesion including telencephalon and thalamus lesions, especially caudate nucleus (24/28). These lesions had well-defined margin from adjacent brain parenchyma, none or mild mass effect and various shape. Most of dogs appeared hyperintensity on T1WI, T2WI, FLAIR, and DWI/ADC, corresponding to chronic infarction. These lesions were histopathologically confirmed atrophic changes and unstained lesion. In conclusion, MRI is the useful method to provide information about ischemic infarction in dogs and the best reproducible ischemic infarction model was developed by using allogenic blood clot.

• 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.

• The Journal of Korean Medicine
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• v.25 no.1
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• pp.117-128
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• 2004

Objectives : This research was performed to investigate effect of Samul-tang-gamibang against focal cerebral ischemic damage after middle cerebral artery occlusion(MCAO). Methods : This research was used rats which were against focal cerebral ischemic damage by MCAO. It was used Zea Longa's theory and Belayev's methods to give rise to focal cerebral ischemic damage by MCAO. After 7days later, we drew out the brain and then had frozen and dyeing it and we had taken a picture to measure of the damaged area in each brain section. We determined the Neurological Index and tested the Foot-fault test and Roatated test to appraise the fall of motion ability result from cerebral ischemic damage. Results : The results of the experiment are as follows. 1. Samul-tang-gamibang reduced infarct size of sample group compared to control group at 7 day after MCAO. 2. Samul-tang-gamibang reduced infarct volume of sample group compared to control group at 7 day after MCAO. 3. Samul-tang-gamibang reduced foot-fault index of sample group compared to control group at 5,7 day after MCAO. Conclusions : Samul-tang-gamibang has protective effects against ischemic brain damage and had significant reduced infarct size and infarct volume of Rt-MCAO.

• The Journal of Korean Medicine
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• v.20 no.4
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• pp.82-92
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• 2000

The purpose of the present study was to explore the proper method for animal stroke model of Oriental medicine To this end, brain ischemia was induced by distal middle cerebral artery occlusion(dMCAO) and proximal middle cerebral artery occlusion(pMCAO) and evaluated with the method of Triphenyl Tetrazolium Chloride (TTC) staining and Swimming Behavior Test. Results demonstrated that first, infarct size and volume of pMCAO group were significantly bigger that those of dMCAO group. Second, analysis of swimming behavior test revealed that the percentage of left turning angles of pMCAO was significantly bigger than that of dMCAO. Third, during swimming behavior test, there were peculiar traces of small successive circles that represent motor dysfunction and conscious disturbance among dMCAO group. The results of the study thus indicate that non-invasive intraluminal method of pMCAO was the appropriate animal stroke model for Oriental medicine in the light of brain ischemia as hemiplesia and conscious disturbance.

• The Journal of Internal Korean Medicine
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• v.31 no.4
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• pp.763-774
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• 2010

Objectives : In condition of brain infarction, irreversible axon damage occurs in central nerve system(CNS), because gliosis becomes physical and mechanical barrier to axonal regeneration. Reactive gliosis induced by ischemic injury such as middle cerebral artery occlusion is involved with up-regulation of GFAP and CD81. The current study is to examine the effect of the Uncariae Ramulus et Uncus on CD81 and GFAP expression in the rat brain following middle cerebral artery occlusion. Methods : In order to study ischemic injuries on brain, infarction was induced by middle cerebral artery occlusion(MCAO) using insertion of a single nylon thread, through the internal carotid artery, into a middle cerebral artery. Cresyl violet staining, cerebral infarction size measurement, immunohistochemistry and microscopic examination were used to detect the expression of CD81 and GFAP and the effect on the infarct size and pyramidal cell death in the brain of the rat with cerebral infarction induced by MCAO. Results : The following results were obtained 1. Measuring the size of cerebral infartion induced by MCAO in the rat after injection of Uncariae Ramulus et Uncus showed the size was decreased. 2. Intravenous injection of Uncariae Ramulus et Uncus showed pyramidal cell death protection in the hippocampus in the MCAO rat. 3. Water extract injection of Uncariae Ramulus et Uncus decreased GFAP expression significantly in the MCAO rat. 4. Uncariae Ramulus et Uncus water extract decreased CD81 expression in the MCAO rat. 5. The administration of water extract of Uncariae Ramulus et Uncus induced up-regulation of c-Fos expression significantly compared with MCAO. 6. The admistration of water extract of Uncariae Ramulus et Uncus increased ERK expression significantly compared with MCAO. Conclusion : We observed that Uncariae Ramulus et Uncus could suppress the reactive gliosis, which disturbs the axonal regeneration in the brain of the rat with cerebral infaction after MCAO by controlling the expression of CD81 and GFAP. The effect may be modulated by the up-regulation of c-Fos and ERK. These results suggest that Uncariae Ramulus et Uncus can be a candidate to regenerate CNS injury.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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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.