• The Journal of Korean Medicine
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• v.30 no.6
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• pp.53-68
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• 2009

Objectives: This study demonstrates the neurological effects of Bojungikki-tang and Bojungikki-tang-gamibang on the focal cerebral ischemia of rats with ischemic damage caused by middle cerebral artery occlusion (MCAO). Methods: Rats were treated with Bojungikki-tang and Bojungikki-tang-gamibang extracts for about five days after MCAO, and the size and volume of cerebral infarction and the ratio of cerebral edema were observed. From the immunohistochemical view, significant changes of outbreak of Bax, Bcl-2, c-Fos, HSP72, and iNOS were observed in the brain tissues. Results: Bojungikki-tang repressed only brain edema and iNOS revelation led by focal cerebral ischemia, when considering significance. In contrast, Bojungikki-tang-gamibang demonstrated significant suppression of cerebral infarction, brain edema, Bax, c-Fos, HSP72, and iNOS induced by focal cerebral ischemia. Conclusions: Bojungikki-tang is considered functional treatment for cerebral ischemic damage; it can be effective to relieve secondary brain edema and immune response. Bojungikki-tang-gamibang can have a direct function to alleviate brain infarct and to control the natural death of nerve cells which cerebral ischemic damage brings about.

• The Korean Journal of Pain
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• v.20 no.2
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• pp.83-91
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• 2007

Background: Cerebral blood vessels are innervated by sympathetic nerves that originate in the superior cervical ganglia (SCG). This study was conducted to determine the effect of an SCG block on brain injury caused by focal cerebral ischemia/reperfusion in a rat model. Methods: Male Sprague-Dawley rats (270-320 g) were randomly assigned to one of three groups (lidocaine, ropivacaine, and control). After brain injury induced by middle cerebral artery (MCA) occlusion/reperfusion, the animals were administered an SCG bloc that consisted of $30{\mu}l$ of 2% lidocaine or 0.75% ropivacaine, with the exception of animals in the control group, which received no treatment. Twenty four hours after brain injury was induced, neurologic scores were assessed and brain samples were collected. The infarct and edema ratios were measured, and DNA fragmented cells were counted in the frontoparietal cortex and the caudoputamen. Results: No significant differences in neurologic scores or edema ratios were observed among the three groups. However, the infarct ratio was significantly lower in the ropivacaine group than in the control group (P < 0.05), and the number of necrotic cells in the caudoputamen of the ropivacaine group was significantly lower than in the control group (P < 0.01). Additionally, the number of necrotic and apoptotic cells in theropivacaine group were significantly lower than inthe control group in both the caudoputamen and the frontoparietal cortex (P < 0.05). Conclusions: Brain injury induced by focal cerebral ischemia/reperfusion was reduced by an SCG block using local anesthetics. This finding suggests that a cervical sympathetic block could be considered as another treatment option for the treatment of cerebral vascular diseases.

• Journal of Korean Neurosurgical Society
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• v.44 no.3
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• pp.159-162
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• 2008

Stenting is a useful alternative treatment modality in carotid artery stenosis patients who are too high-risk to undergo carotid endarterectomy (CEA). We report a case of contralateral cerebral infarction after stenting for extracranial carotid stenosis. A 78-year-old woman was admitted to the hospital with left-sided weakness. Based on magnetic resonance imaging (MRI) of the brain and conventional angiography, she was diagnosed with an acute watershed infarct of the right hemisphere secondary to severe carotid stenosis. Stenting was performed for treatment of the right carotid artery stenosis after a one-week cerebral angiogram was completed. Thirty minutes after stent placement, the patient exhibited a generalized seizure. Four hours later, brain MRI revealed left hemispheric cerebral infarction. Complex aorta-like arch elongation, tortuosity, calcification, and acute angulation at the origin of the supra-aortic arteries may increase the risk of procedural complications. In our case, we suggest that difficult carotid artery catheterization, with aggressive maneuvering during stenting, likely injured the tortuous, atherosclerotic aortic arch, and led to infarction of the contralateral cerebral hemisphere by thromboemboli formed on the wall of the atherosclerotic aorta.

• The Korea Journal of Herbology
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• v.23 no.2
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• pp.159-168
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• 2008

Objectives : The present study has been undertaken to investigate the effects of Dipsaci Radix on Muscle Fiber Atrophy and MyoD Expression in Gastrocnemius of MCAO Rats Methods : In order to investigate effects of Dipsaci radix on the skeletal muscle atrophy following stroke, cerebral infarct was induced by the middle cerebral artery occlusion (MCAO) in the rats. Water extract of Dipsaci radix (184.4 mg/100 g) was treated for 4 weeks, once a day orally, after the MCAO. Effects were evaluated with muscle fiber type composition and cross-sectioned area of muscle fibers in gastrocnemius of the unaffected & affected hind limbs. And MyoD protein expression in gastrocnemius was demonstrated with immunohistochemistry and western blotting. Results : Obtained results were as follows; 1. Infarct volume was not attenuated by Dipsaci radix treatment in the MCAO rats. 2. At the affected-side hind limb of the MCAO rats, the increase of type-I fibers and the decrease of type-II fibers were induced by Dipsaci radix treatment. 3. At the affected-side hind limb of the MCAO rats, decreases of cross-sectioned areas of type-I and type-II fibers were attenuated by Dipsaci radix treatment. 4. At the affected-side hind limb of the MCAO rats, MyoD positive cells were increased by Dipsaci radix treatment. 5. At the affected-side hind limb of the MCAO rats, MyoD expressions were increased by Dipsaci radix treatment. Conclusions : These results suggest that Dipsaci radix has a protective effect against muscle atrophy, through the inhibition of the muscle cell apoptosis, following the central nervous system demage.

• Clinical and Experimental Pediatrics
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• v.64 no.8
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• pp.422-429
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• 2021

Background: Carnosine has antioxidative and neuroprotective properties against hypoxic-ischemic (HI) brain injury. Hypothermia is used as a therapeutic tool for HI encephalopathy in newborn infants with perinatal asphyxia. However, the combined effects of these therapies are unknown. Purpose: Here we investigated the effects of combined carnosine and hypothermia therapy on HI brain injury in neonatal rats. Methods: Postnatal day 7 (P7) rats were subjected to HI brain injury and randomly assigned to 4 groups: vehicle; carnosine alone; vehicle and hypothermia; and carnosine and hypothermia. Carnosine (250 mg/kg) was intraperitoneally administered at 3 points: immediately following HI injury, 24 hours later, and 48 hours later. Hypothermia was performed by placing the rats in a chamber maintained at 27℃ for 3 hours to induce whole-body cooling. Sham-treated rats were also included as a normal control. The rats were euthanized for experiments at P10, P14, and P35. Histological and morphological analyses, in situ zymography, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assays, and immunofluorescence studies were conducted to investigate the neuroprotective effects of the various interventional treatments. Results: Vehicle-treated P10 rats with HI injury showed an increased infarct volume compared to sham-treated rats during the triphenyltetrazolium chloride staining study. Hematoxylin and eosin staining revealed that vehicle-treated P35 rats with HI injury had decreased brain volume in the affected hemisphere. Compared to the vehicle group, carnosine and hypothermia alone did not result in any protective effects against HI brain injury. However, a combination of carnosine and hypothermia effectively reduced the extent of brain damage. The results of in situ zymography, TUNEL assays, and immunofluorescence studies showed that neuroprotective effects were achieved with combination therapy only. Conclusion: Carnosine and hypothermia may have synergistic neuroprotective effects against brain damage following HI injury.

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.3
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• pp.239-252
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• 2024

Dexmedetomidine displays multiple mechanisms of neuroprotection in ameliorating ischemic brain injury. In this study, we explored the beneficial effects of dexmedetomidine on blood-brain barrier (BBB) integrity and neuroinflammation in cerebral ischemia/reperfusion injury. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 1.5 h and reperfusion for 24 h to establish a rat model of cerebral ischemia/reperfusion injury. Dexmedetomidine (9 ㎍/kg) was administered to rats 30 min after MCAO through intravenous injection, and SB203580 (a p38 MAPK inhibitor, 200 ㎍/kg) was injected intraperitoneally 30 min before MCAO. Brain damages were evaluated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, Nissl staining, and brain water content assessment. BBB permeability was examined by Evans blue staining. Expression levels of claudin-5, zonula occludens-1, occludin, and matrix metalloproteinase-9 (MMP-9) as well as M1/M2 phenotypes-associated markers were assessed using immunofluorescence, RT-qPCR, Western blotting, and gelatin zymography. Enzyme-linked immunosorbent assay was used to examine inflammatory cytokine levels. We found that dexmedetomidine or SB203580 attenuated infarct volume, brain edema, BBB permeability, and neuroinflammation, and promoted M2 microglial polarization after cerebral ischemia/reperfusion injury. Increased MMP-9 activity by ischemia/reperfusion injury was inhibited by dexmedetomidine or SB203580. Dexmedetomidine inhibited the activation of the ERK, JNK, and p38 MAPK pathways. Moreover, activation of JNK or p38 MAPK reversed the protective effects of dexmedetomidine against ischemic brain injury. Overall, dexmedetomidine ameliorated brain injury by alleviating BBB permeability and promoting M2 polarization in experimental cerebral ischemia/reperfusion injury model by inhibiting the activation of JNK and p38 MAPK pathways.

• Biomolecules & Therapeutics
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• v.28 no.2
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• pp.152-162
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• 2020

Cerebral ischemia exhibits a multiplicity of pathophysiological mechanisms. During ischemic stroke, the reactive oxygen species (ROS) concentration rises to a peak during reperfusion, possibly underlying neuronal death. Recombinant human erythropoietin (EPO) supplementation is one method of treating neurodegenerative disease by reducing the generation of ROS. We investigated the therapeutic effect of PEGylated EPO (P-EPO) on ischemic stroke. Mice were administered P-EPO (5,000 U/kg) via intravenous injection, and middle cerebral artery occlusion (MCAO) followed by reperfusion was performed to induce in vivo ischemic stroke. P-EPO ameliorated MCAO-induced neurological deficit and reduced behavioral disorder and the infarct area. Moreover, lipid peroxidation, expression of inflammatory proteins (cyclooxygenase-2 and inducible nitric oxide synthase), and cytokine levels in blood were reduced by the P-EPO treatment. In addition, higher activation of nuclear factor kappa B (NF-κB) was found in the brain after MCAO, but NF-κB activation was reduced in the P-EPO-injected group. Treatment with the NF-κB inhibitor PS-1145 (5 mg/kg) abolished the P-EPO-induced reduction of infarct volume, neuronal death, neuroinflammation, and oxidative stress. Moreover, P-EPO was more effective than EPO (5,000 U/kg) and similar to a tissue plasminogen activator (10 mg/kg). An in vitro study revealed that P-EPO (25, 50, and 100 U/mL) treatment protected against rotenone (100 nM)-induced neuronal loss, neuroinflammation, oxidative stress, and NF-κB activity. These results indicate that the administration of P-EPO exerted neuroprotective effects on cerebral ischemia damage through anti-oxidant and anti-inflammatory properties by inhibiting NF-κB activation.

• Korean Journal of Oriental Medicine
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• v.13 no.1 s.19
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• pp.153-160
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• 2007

In the post-genome era, analysis of the cellular transcriptome using microarray or the cellular proteome using a 2-D gel electrophoresis and MALDI-TOF mass spectrometry are most widely used. Stroke is one of the most important causes of death along with cancer and cardiac disease. When pathological change of cells in developed from cerebral ischemia accompanied by stroke administration of neuroprotective drugs before stroke can decreases the degeneration of neuronal cells. The purpose of the present study was to assess the neuroprotective effect and protein expression after administration of P004, middle cerebral artery model of cerebral ischemia in rats. SD rats were subjected to middle cerebral artery occlusion. P004 (1,000 mg/kg) was administered 2 times at 0, 90 minutes after middle cerebral artery occlusion (MCAo). Rats were killed at 48 hours, and infarct area and volume were determined by histology and computerized image analysis. We investigated the protein expression profile on the global ischemia induced by MCAo. This proteomic analysis enable us to identify several proteins differently expressed in infarct brain tissue. The aims of this study were to do investigation comparing the neuroprotection activities of P004 and to understand the mechanism of acted as neuroprotective drug.

• Molecules and Cells
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• v.20 no.3
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• pp.354-360
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• 2005

Neuronal damage subsequent to transient cerebral ischemia is a multifactorial process involving several overlapping mechanisms. Gangliosides, sialic acid-conjugated glycosphingolipids, reduce the severity of acute brain damage in vitro. However their in vivo effects on the cerebral cortex damaged by ischemic infarct are unknown. To assess the possible protective role of gangliosides we examined their expression in the cerebral cortex damaged by ischemic infarct in the rat. Ischemia was induced by middle cerebral artery (MCA) occlusion, and the resulting damage was observed by staining with 2, 3, 5-triphenylterazolium chloride (TTC). High-performance thin-layer chromatography (HPTLC) showed that gangliosides GM3 and GM1 increased in the damaged cerebral cortex, and immunofluorescence microscopy also revealed a significant change in expression of GM1. In addition, in situ hybridization demonstrated an increase in the mRNA for ganglioside GM3 synthase. These results suggest that gangliosides GM1 and GM3 may be synthesized in vivo to protect the cerebral cortex from ischemic damage.

• Proceedings of the Korean Society of Developmental Biology Conference
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• 2003.10a
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• pp.71-71
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• 2003

Human umbilical cord blood cells(HUCBC) are rich in mesenchymal progenitor cells, endothelial cell precursors and hematopoietic cells. HUCBC have been used as a source of transplantable stem and progenitor cells. However, little is known about survival and development of HUCBC transplantation in the CNS. Estrogen has a neuroprotective potential against oxidative stress-induced cell death so has an effect on reducing infarct size of ischemic brain. We investigated the potential use of HUCBC as donor cells and tested whether estrogen mediates intravenously infused HUCBC enter and survive in ischemic brain. PKH26 labeled mononuclear fraction of HUCBC were injected into the tail vein of ischemic OVX rat brain with or without $17\beta$-estradiol valerate(EV). Under fluorescence microscopy, labeled cells were observed in the brain section. Significantly more cells were found in the ischemic brain than in the non-ischemic brain. HUCBC transplanted into ischemic brain could migrate and survive. Some of cells have shown neuronal like cells in hippocampus, striatum and cortex tissues. These result suggest that estrogen reduces ischemic damage and increases the migration of human umbilical cord blood cells. This Study was supported by the Korea Science and Engineering Foundation(KOSEF) though the Biohealth Products Research Center(BPRC), Inje University, Korea.