• Journal of Physiology & Pathology in Korean Medicine
• /
• v.23 no.4
• /
• pp.866-871
• /
• 2009

Brain edema is a major importance in the pathophysiology of CNS injuries including stroke. Ischemic brain edema results from both cytotoxic edema, which is severe in astrocytes at early stage, and vasogenic edema caused by excessive blood-brain barrier (BBB) permeability. The present study was performed to determine the effect of Rhei Rhizoma on brain edema induced by middle cerebral artery occlusion (MCAO) in the rats. The neurological symptom, total infarct volume and edema index caused by MCAO were measured. The changes of Matrix Metalloproteinase-9 (MMP-9) and inducible nitric oxide synthase (iNOS) immunoreactivities were also observed. We found that Rhei Rhizoma extract improved the neurological symptom and attenuated the total infarct volume and brain edema caused by ischemic insult. Rhei Rhizoma extract also attenuated the expression of MMP-9 and iNOS. This results suggest that Rhei Rhizoma has a protective effect on the brain edema caused by ischemic insult.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 2001.11a
• /
• pp.85-85
• /
• 2001

Sam-Hwang-Sa-Shim-Tang(SHSST), a traditional Chinese medicine, composed of Rhei rhizoma, Scutellaria radix, and Coptidis rhizoma were used in the several disease including hypertension, constipation, and hemorrhage. In the present study, we investigated the neuroprotective effects of SHSST and its ingredients on the ischemia/ reperfusion-induced brain injury was evaluated in the rat brain. Ischemia was induced by intraluminal occlusion of the right middle cerebral artery for 120 min and reperfusion was continued for 22 h. SHSST (450 mg/kg), Rhei rhii oma (100 mg/kg), Coptidis rhizoma (100 mg/kg), and Scutellaria radik (100 mg/kg) were orally administered twice, promptly prior to reperfusion and 2 h after the repefusion. Total infarction volume in the ipsilateral hemisphere of ischemia/ reperfusion rats was significantly lowed by the treatments of SHSST (39.2%) and Scutellaria radix (66.5%). However, Coptidis rhizoma did not show any significant effects on the total infarct volume. The inhibiting effect of Scutellaria radix on the total infarct volume was more potent than that of SHSST. In addition, Scutellaria radix significantly inhibited myeloperoxidase (MPO) activity, an index of neutrophil infiltration in ischemic brain tissue. However, there was marked mismatch between total infarct volume and MPO activity in the Scutellaria radix-treated rats. Our findings suggest that Scutellaria radix as an ingredient of SHSST plays a protective role in ischemia-induced brain injury by inhibiting neutrophil infiltration. The effects of Rhei rhizoma on transient brain ischemia-induced neuronal injury are under study.

• The Journal of the Korea Contents Association
• /
• v.19 no.7
• /
• pp.186-191
• /
• 2019

Introduction: In aged people, stroke incidence is increased. But standardized experimental animal protocol study for the research of stroke therapy is rare. There is little report on the success rate of cerebral artery occlusion model using standardized Nylon thread length of precise thread end-size controlled. Method: In this study, the operator intended the occlusion of middle cerebral artery (MCA) using $0.18{\pm}0.02mm$ end 5-0 Nylon thread. Middle cerebral artery occlusion was induced for 60min under isoflurane anesthesia. After 60min, the operator removed the Nylon thread and reperfusion was induced for 23hrs. The mice was killed 23hrs after reperfusion and infarction area of brain was confirmed by 1.5% TTC (2,3,5-tryphenyl tetrazolium chloride) staining. Results: According to end size and insert length of Nylon thread, Middle cerebral artery occlusion (n=50), internal carotid artery occlusion (n= 14), distal middle cerebral artery occlusion (n= 36), anterior cerebral artery (n= 1) were induced. And no infarction (n= 50) was observed. Conclusion: According to weight of mice, the operator induced reversible cerebral artery occlusion model by different insert length (30.0~36.9g : 9.0mm, 37.0~40.0g : 9.5mm) of Nylon thread. Success of cerebral artery occlusion model was confirmed by checking infarction area using TTC staining. The success rate (66.9%, 101/151) of reversible cerebral artery occlusion model in the mouse and the operational conditions are shown.

• Journal of Korean Neurosurgical Society
• /
• v.50 no.3
• /
• pp.173-178
• /
• 2011

Objective : The rat middle cerebral artery thread-occlusion model has been widely used to investigate the pathophysiological mechanisms of stroke and to develop therapeutic treatment. This study was conducted to analyze energy metabolism, apoptotic signal pathways, and genetic changes in the hippocampus of the ischemic rat brain. Methods : Focal transient cerebral ischemia was induced by obstructing the middle cerebral artery for two hours. After 24 hours, the induction of ischemia was confirmed by the measurement of infarct size using 2,3,5-triphenyltetrazolium chloride staining. A cDNA microarray assay was performed after isolating the hippocampus, and was used to examine changes in genetic expression patterns. Results : According to the cDNA microarray analysis, a total of 1,882 and 2,237 genes showed more than a 2-fold increase and more than a 2-fold decrease, respectively. When the genes were classified according to signal pathways, genes related with oxidative phosphorylation were found most frequently. There are several apoptotic genes that are known to be expressed during ischemic brain damage, including Akt2 and Tnfrsf1a. In this study, the expression of these genes was observed to increase by more than 2-fold. As energy metabolism related genes grew, ischemic brain damage was affected, and the expression of important genes related to apoptosis was increased/decreased.Conclusion : Our analysis revealed a significant change in the expression of energy metabolism related genes (Atp6v0d1, Atp5g2, etc.) in the hippocampus of the ischemic rat brain. Based on this data, we feel these genes have the potential to be target genes used for the development of therapeutic agents for ischemic stroke.

• Korean Journal of Medicinal Crop Science
• /
• v.19 no.1
• /
• pp.31-37
• /
• 2011

Previous work demonstrated that an ethanol extract (HS0608) of a mixture of three medicinal plants of Curcuma longae radix, Phellinus linteus, and Scutellariae radix markedly inhibits $A{\beta}$ (25-35)-induced neurotoxicity. The present study was performed to further verify the neuroprotective effect of HS0608 on oxidative and ischemic cerebral injury using cultured rat cortical neurons and rats. Exposure of cultured cortical neurons to $100\;{\mu}M$ hydrogen peroxide ($H_2O_2$) induced neuronal apoptotic death. At $10-100{\mu}g/ml$, HS0608 inhibited neuronal death, elevation of intracellular calcium concentration ($[Ca^{2+}]_i$), and generation of reactive oxygen species (ROS) induced by $H_2O_2$ in primary cultures of rat cortical neurons. In vivo, HS0608 prevented cerebral ischemic injury induced by 2-h middle cerebral artery occlusion (MCAO) and 24-h reperfusion. The ischemic infarct and edema were significantly reduced in rats that received HS0608 (200 mg/kg). These results suggest that the anti-oxidative properties of HS0608 may be responsible for its neuroprotective effect against focal cerebral ischemic injury and that HS0608 may have a therapeutic role in neurodegenerative diseases such as stroke.

• Korean Journal of Radiology
• /
• v.19 no.6
• /
• pp.1161-1171
• /
• 2018

Objective: The aim of this study was to investigate diffusion tensor (DT) imaging-derived properties of benign oligemia, true "at risk" penumbra (TP), and the infarct core (IC) during the first 3 hours of stroke onset. Materials and Methods: The study was approved by the local animal care and use committee. DT imaging data were obtained from 14 rats after permanent middle cerebral artery occlusion (pMCAO) using a 7T magnetic resonance scanner (Bruker) in room air. Relative cerebral blood flow and apparent diffusion coefficient (ADC) maps were generated to define oligemia, TP, IC, and normal tissue (NT) every 30 minutes up to 3 hours. Relative fractional anisotropy (rFA), pure anisotropy (rq), diffusion magnitude (rL), ADC (rADC), axial diffusivity (rAD), and radial diffusivity (rRD) values were derived by comparison with the contralateral normal brain. Results: The mean volume of oligemia was $24.7{\pm}14.1mm^3$, that of TP was $81.3{\pm}62.6mm^3$, and that of IC was $123.0{\pm}85.2mm^3$ at 30 minutes after pMCAO. rFA showed an initial paradoxical 10% increase in IC and TP, and declined afterward. The rq, rL, rADC, rAD, and rRD showed an initial discrepant decrease in IC (from -24% to -36%) as compared with TP (from -7% to -13%). Significant differences (p < 0.05) in metrics, except rFA, were found between tissue subtypes in the first 2.5 hours. The rq demonstrated the best overall performance in discriminating TP from IC (accuracy = 92.6%, area under curve = 0.93) and the optimal cutoff value was -33.90%. The metric values for oligemia and NT remained similar at all time points. Conclusion: Benign oligemia is small and remains microstructurally normal under pMCAO. TP and IC show a distinct evolution of DT-derived properties within the first 3 hours of stroke onset, and are thus potentially useful in predicting the fate of ischemic brain.

• Biomolecules & Therapeutics
• /
• v.23 no.6
• /
• pp.531-538
• /
• 2015

Preceding infection or inflammation such as bacterial meningitis has been associated with poor outcomes after stroke. Previously, we reported that intracorpus callosum microinjection of lipopolysaccharides (LPS) strongly accelerated the ischemia/reperfusionevoked brain tissue damage via recruiting inflammatory cells into the ischemic lesion. Simvastatin, 3-hydroxy-3-methylgultaryl (HMG)-CoA reductase inhibitor, has been shown to reduce inflammatory responses in vascular diseases. Thus, we investigated whether simvastatin could reduce the LPS-accelerated ischemic injury. Simvastatin (20 mg/kg) was orally administered to rats prior to cerebral ischemic insults (4 times at 72, 48, 25, and 1-h pre-ischemia). LPS was microinjected into rat corpus callosum 1 day before the ischemic injury. Treatment of simvastatin reduced the LPS-accelerated infarct size by 73%, and decreased the ischemia/reperfusion-induced expressions of pro-inflammatory mediators such as iNOS, COX-2 and IL-$1{\beta}$ in LPS-injected rat brains. However, simvastatin did not reduce the infiltration of microglial/macrophageal cells into the LPS-pretreated brain lesion. In vitro migration assay also showed that simvastatin did not inhibit the monocyte chemoattractant protein-1-evoked migration of microglial/macrophageal cells. Instead, simvastatin inhibited the nuclear translocation of NF-${\kappa}B$, a key signaling event in expressions of various proinflammatory mediators, by decreasing the degradation of $I{\kappa}B$. The present results indicate that simvastatin may be beneficial particularly to the accelerated cerebral ischemic injury under inflammatory or infectious conditions.

• The Korean Journal of Physiology and Pharmacology
• /
• v.13 no.3
• /
• pp.257-263
• /
• 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.

• Journal of Korean Neurosurgical Society
• /
• v.42 no.4
• /
• pp.326-330
• /
• 2007

Objective : Stroke is the most prevalent disease involving the central nervous system. Since medical modalities are sometimes ineffective for the acute edema following massive infarction, surgical decompression may be an effective option when medical treatments fail. The present study was undertaken to assess the outcome and prognostic factors of decompressive surgery in life threatening acute, severe, brain infarction. Methods : We retrospectively analyzed twenty-six patients (17 males and 9 females; average age, 49.7yrs) who underwent decompressive surgery for severe cerebral or cerebellar infarction from January 2003 to December 2006. Surgical indication was based on the clinical signs such as neurological deterioration, pupillary reflex, and radiological findings. Clinical outcome was assessed by Glasgow Outcome Scale (GOS). Results : Of the 26 patients, 5 (19.2%) showed good recovery, 5 (19.2%) showed moderate disability, 2 (7.7%) severe disability, 6 (23.1%) persistent experienced vegetative state, and 8 (30.8%) death. In this study, the surgical decompression improved outcome for cerebellar infarction, but decompressive surgery did not show a good result for MCA infarction (30.8% overall mortality vs 100% mortality). The dominant-hemisphere infarcts showed worse prognosis, compared with nondominant-hemisphere infarcts (54.5% vs 70%). Poor prognostic factors were diabetes mellitus, dominant-hemisphere infarcts and low preoperative Glasgow Coma Scale (GCS) score. Conclusion : The patients who exhibit clinical deterioration despite aggressive medical management following severe cerebral infarction should be considered for decompressive surgery. For better outcome, prompt surgical treatment is mandatory. We recommend that patients with severe cerebral infarction should be referred to neurosurgical department primarily in emergency setting or as early as possible for such prompt surgical treatment.

• Korean Journal of Radiology
• /
• v.1 no.1
• /
• pp.5-10
• /
• 2000

Objective: To describe the neuroradiologic findings of primary antiphospholipid antibody syndrome (PAPS). Materials and Methods: During a recent two-year period, abnormally elevated antiphospholipid antibodies were detected in a total of 751 patients. In any cases in which risk factors for stroke were detected - hypertension, diabetes mellitus, hyperlipidemia, smoking, and the presence of SLE or other connective tissue diseases - PAPS was not diagnosed. Neuroradiologic studies were performed in 11 of 32 patients with PAPS. We retrospectively reviewed brain CT (n = 7), MR (n = 8), and cerebral angiography (n = 8) in 11 patients with special attention to the presence of brain parenchymal lesions and cerebral arterial or venous abnormalities. Results: CT or MR findings of PAPS included nonspecific multiple hyper-intensity foci in deep white matter on T2-weighted images (5/11), a large infarct in the territory of the middle cerebral artery (4/11), diffuse cortical atrophy (2/11), focal hemorrhage (2/11), and dural sinus thrombosis (1/11). Angiographic findings were normal (5/8) or reflected either occlusion of a large cerebral artery (2/8) or dural sinus thrombosis (1/8). Conclusion: Neuroradiologic findings of PAPS are nonspecific but in young or middle- aged adults who show the above mentioned CT or MR findings, and in whom risk factors for stroke are not present, the condition should be suspected.