• 대한한의학회지
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• 제26권2호
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• pp.77-84
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• 2005

Objectives: Chunghyul-dan is a combinatorial herbal medicine, and previous studies reported it had therapeutic effects for microangiopathy, which is a major part. in the progression of stroke, as well as having anti-hypertensive, anti-hyperlipidemic, anti-apoptotic, anti-oxidative, and anti-inflammatory activities, Therefore, we examined the inhibitory effect of Chunghyul-dan on stroke occurrence in patients with silent brain infarction. Methods: We prescribed Chunghyul-dan at 600 mg a day to patients with silent brain infarction confirmed by brain MRI, and monitored stroke occurrence, drug compliances, and adverse effects for 1 year, We then performed follow-up brain MRI to detect new vascular lesions after 1 year of Chunghyul-dan medication. As for the subjects lost to follow-up, we assessed their prognosis after 1 year by telephone. Results: There were twenty-one subjects who were treated with Chunghyul-dan for more than 1 year, None of them experienced new clinical syndromes characterized by rapidly developing clinical symptoms and signs of focal and at times global loss of brain function, which could be accompanied with evidence of stroke occurrence, or any adverse effects during the Chunghyul-dan medication period. These results might be explained by various biochemical effects of Chunghyul-dan on microangiopathy, which is closely related with cell cycle progression, hypertension, hyperlipidemia, vascular inflammation, and oxidative damage. Of the 10 subjects lost to follow-up, six were reached; two of them had stroke occurrence. Conclusions: We suggest Chunghyul-dan could be useful for prevention of stroke occurrence in patients with silent brain infarction by preventing the progression of microangiopathy. Further study with a randomized controlled trial is needed to confirm this suggestion.

• Journal of Acupuncture Research
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• 제36권3호
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• pp.140-146
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• 2019

Background: This study investigated the effects of Vipera lebetina turanica snake venom (SV) on cerebral infarction induced by middle cerebral artery occlusion in mice. Methods: Following cerebral infarction, SV was injected intravenously or added to BV2 cell culture. Tissue injury was detected using triphenyltetrazolium chloride (TTC) staining, neurological deficit score, NO, ROS, and GSH/GSSG assays, qPCR, Western blot, and cell viability. Results: Cerebral infarction caused by middle cerebral artery occlusion as observed by TTC staining, showed SV inhibited cell death, reducing the number of brain cells injured due to infarction. SV treatment for cerebral infarction showed a significant decrease in abnormal behavior, as determined by the neurological deficit score. The oxidation and inflammation of the cells that had cerebral infarction caused by middle cerebral artery occlusion (NO assay, ROS, GSH/GSSG assay, and qPCR), showed significant protection by SV. Western blot of brain infarction cells showed the expression of iNOS, COX-2, p-IkB-${\alpha}$, P38, p-JNK, p-ERK to be lower in the SV group. In addition, the expression of IkB increased. BV2 cells were viable when treated with SV at $20{\mu}g/mL$ or less. Western blot of BV2 cells, treated with 0.625, 1.5, $2.5{\mu}g/mL$ of SV, showed a significant decrease in the expression of p-IkB-${\alpha}$, p-JNK, iNOS, and COX-2 on BV2 cells induced by LPS. Conclusion: SV showed anti-inflammatory and anti-oxidant effects against cerebral infarction and inflammation.

• 한국임상수의학회지
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• 제33권1호
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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.

• Journal of Korean Neurosurgical Society
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• 제42권4호
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• pp.331-336
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• 2007

Objective : The aim of this study was to analyze the treatment results and prognostic factors in patients with massive cerebral infarction who underwent decompressive craniectomy. Methods : From January 2000 to December 2005, we performed decompressive craniectomy in 24 patients with massive cerebral infarction. We retrospectively reviewed the medical records, radiological findings, initial clinical assessment using the Glasgow Coma Scale, serial computerized tomography (CT) with measurement of midline and septum pellucidum shift, and cerebral infarction territories. Patients were evaluated based on the following factors : the pre- and post-operative midline shifting on CT scan, infarction area or its dominancy, consciousness level, pupillary light reflex and Glasgow Outcome Scale. Results : All 24 patients (11 men, 13 women; mean age, 63 years; right middle cerebral artery (MCA) territory, 17 patients; left MCA territory, 7 patients) were treated with large decompressive craniectomy and duroplasty. The average time interval between the onset of symptoms and surgical decompression was 2.5 days. The mean Glasgow Coma Scale was 12.4 on admission and 8.3 preoperatively. Of the 24 surgically treated patients, the good outcome group (Group 2 : GOS 4-5) comprised 9 cases and the poor outcome group (Group1 : GOS 1-3) comprised 15 cases. Conclusion : We consider decompressive craniectomy for large hemispheric infarction as a life-saving procedure. Good preoperative GCS, late clinical deterioration, small size of the infarction area, absence of anisocoria, and preoperative midline shift less than 11mm were considered to be positive predictors of good outcome. Careful patient selection based on the above-mentioned factors and early operation may improve the functional outcome of surgical management for large hemispheric infarction.

• 대한핵의학회지
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• 제38권6호
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• pp.528-531
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• 2004

목적: PET은 해상도 한계로 인하여 각종 소동물 실험에서 영상화하는데 현실적인 어려움이 많았다. 마이크로 PET의 등장으로 랫트나 마우스와 같은 실험 동물을 보다 나은 해상도로 평가할 수 있으나 실험 동물의 크기가 작기 때문에 영상이 사람에서와 같이 선명하지는 않다. 고양이와 같은 중소형 동물은 뇌가 상대적으로 크기 때문에 마이크로PET을 이용하여 보다 선명한 영상을 얻을 수 있다. 이 연구에서는 고양이 뇌 경색을 구축하고 마이크로PET으로 평가하였으며 시간에 따른 변화도 같이 평가하였다. 대상 및 방법 : 수컷 고양이 2마리를 사용하였으며, 체중은 각각 3.0 kg, 3.3 kg 이었다. Xylazine과 Ketamine HCl으로 마취하였다. 고양이 대천문에서 오른쪽으로 1cm되는 곳에 burr 구멍을 뚫은 후 30 G 바늘을 삽입하여 collagenase type IV 10 ${\mu}l$를 5분에 걸쳐 주사하여 뇌 경색 모델을 만들었다. 경색을 만든 후 1일, 11일, 32일 후에 마이크로 PET R4 scanner (Concorde Microsystems Inc., Knoxville, TN)을 사용하여 $^{18}F$-FDG PET 영상을 얻었다. 추가로 경색 13, 47일에 사람용 PET scanner (Gemini, Philips medical systems, CA, USA)를 사용하여 FDG-PET 촬영을 하였다. 결과: 성공적으로 고양이 뇌출혈경색 모델을 만들 수 있었으며 마이크로 PET으로 얻은 영상에서 병변의 당 대사는 시간이 지남에 따라서 호전되었다. 사람용 PET으로도 병변을 확인할 수 있었다. 결론: 고양이 2마리에 두개골을 통해 collagenase를 주입하여 성공적으로 출혈성 뇌 경색 모델을 만들었으며 $^{18}F$-FDG 마이크로 PET으로 영상화할 수 있었다.

• Biomolecules & Therapeutics
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• 제30권1호
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• pp.55-63
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• 2022

Oleanolic acid (OA), a natural pentacyclic triterpenoid, has been reported to exert protective effects against several neurological diseases through its anti-oxidative and anti-inflammatory activities. The goal of the present study was to evaluate the therapeutic potential of OA against acute and chronic brain injuries after ischemic stroke using a mouse model of transient middle cerebral artery occlusion (tMCAO, MCAO/reperfusion). OA administration immediately after reperfusion significantly attenuated acute brain injuries including brain infarction, functional neurological deficits, and neuronal apoptosis. Moreover, delayed administration of OA (at 3 h after reperfusion) attenuated brain infarction and improved functional neurological deficits during the acute phase. Such neuroprotective effects were associated with attenuation of microglial activation and lipid peroxidation in the injured brain after the tMCAO challenge. OA also attenuated NLRP3 inflammasome activation in activated microglia during the acute phase. In addition, daily administration of OA for 7 days starting from either immediately after reperfusion or 1 day after reperfusion significantly improved functional neurological deficits and attenuated brain tissue loss up to 21 days after the tMCAO challenge; these findings supported therapeutic effects of OA against ischemic stroke-induced chronic brain injury. Together, these findings showed that OA exerted neuroprotective effects against both acute and chronic brain injuries after tMCAO challenge, suggesting that OA is a potential therapeutic agent to treat ischemic stroke.

• Journal of Korean Neurosurgical Society
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• 제42권4호
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• pp.337-341
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• 2007

Objective : Repeated administration of mannitol in the setting of large hemispheric infarction is a controversial and poorly defined therapeutic intervention. This study was performed to examine the effects of multiple-dose mannitol on a brain edema after large hemispheric infarction. Methods : A middle cerebral artery was occluded with the rat suture model for 6 hours and reperfused in 22 rats. The rats were randomly assigned to either control (n=10) or the mannitol-treated group (n=12) in which intravenous mannitol infusions (0.8 g/kg) were performed six times every four hours. After staining a brain slice with 2,3,5-triphenyltetrazolium chloride, the weight of hemispheres, infarcted (IH) and contralateral (CH), and the IH/CH weight ratio were examined, and then hemispheric accumulation of mannitol was photometrically evaluated based on formation of NADH catalyzed by mannitol dehydrogenase. Results : Mannitol administration produced changes in body weight of $-7.6{\pm}1.1%$, increased plasma osmolality to $312{\pm}8\;mOsm/L$. It remarkably increased weight of IH ($0.77{\pm}0.06\;gm$ versus $0.68{\pm}0.03\;gm$ : p<0.01) and the IH/CH weight ratio ($1.23{\pm}0.07$ versus $1.12{\pm}0.05$ : p<0.01). The photometric absorption at 340 nm of the cerebral tissue in the mannitol-treated group was increased to $0.375{\pm}0.071$ and $0.239{\pm}0.051$ in the IH and CH, respectively from $0.167{\pm}0.082$ and $0.162{\pm}0.091$ in the IH and CH of the control group (p<0.01). Conclusion : Multiple-dose mannitol is likely to aggravate cerebral edema due to parenchymal accumulation of mannitol in the infarcted brain tissue.

• The Korean Journal of Physiology and Pharmacology
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• 제11권3호
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• pp.85-88
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• 2007

Matrix metalloproteinases (MMPs) can degrade a wide range of extracellular matrix components. It has been reported that MMP-9 are activated after focal ischemia in experimental animals. (-)-Epigallocatechin-3-gallate (EGCG), a major constituent of green tea polyphenols, is a potent free radical scavenger and reduces the neuronal damage caused by oxygen free radicals. And it has been known that EGCG could reduce the infarction volume in focal brain ischemia and inhibit MMP-9 activity. To delineate the relationship between the anti-ischemic action and the MMP-9-inhibiting action of EGCG, we investigated the effect of EGCG on brain infarction and the activity of matrix metalloproteinase-9 induced by permanent middle cerebral artery occlusion (pMCAO) in ICR mice. EGCG (40 mg/kg, i.p. $15{\sim}30min$ prior to MCAO) significantly decreased infarction volume at 24 hr after MCAO. GM 6001 (50 mg/kg, i.p. $15{\sim}30min$ prior to MCAO), a MMP inhibitor, also significantly reduced infarction volume. In zymogram, MMP-9 activities began to increase at ipsilateral cortex at 2 hr after MCAO, and the increments of MMP-9 activities were attenuated by EGCG treatment. Western blot for MMP-9 also showed patterns similar to that of zymogram. These findings demonstrate that the anti-ischemic action of EGCG ire mouse focal cerebral ischemia involves its inhibitory effect on MMP-9.

• 대한핵의학회지
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• 제35권6호
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• pp.343-351
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• 2001

Cerebral post-ischemic hyperperfusion has been observed at the acute and subacute periods of ischemic stroke. In the animal stroke model, early post-ischemic hyperperfusion is the mark of recanalization of the occluded artery with reperfusion. In the PET studios of both humans and experimental animals, early post-ischemic hyperperfusion is not a key factor in the development of tissue infarction and indicates the spontaneous reperfusion of the ischemic brain tissue without late infarction or with small infarction. But late post-ischemic hyperperfusion shows the worse prognosis with reperfusion injury associated with brain tissue necrosis. Early post-ischemic hyperperfusion defined by PET and SPECT may be useful in predicting the prognosis of ischemic stroke and the effect of thrombolytic therapy.

• Journal of Korean Neurosurgical Society
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• 제41권6호
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• pp.411-413
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• 2007

We report on a diabetic 52-year-old man who complained ocular floating sensation, headache and dizziness, in whom a left parieto-occipital dural ateriovenous fistulas [DAVFs], fed by bilateral superficial temporal arteries and occipital artery, drained into the cortical vein of the left parieto-occipital convexity. Because the patient's chief complaint was ocular symptom for diabetic retinopathy, we initially didn't consider an DAVFs until brain magnetic resonance imaging [MRI] was done. Diffusion-weighted brain MRI revealed acute cerebral infarction and microhemorrhage in the lesion. Transarterial embolization with mixture of glue and lipiodol obliterated the DAVFs completely. Although the DAVFs fed by multi-arteries, the fistulous portion has been disappeared after embolization via an only left occipital artery Endovascular embolization of the fistula led to symptomatic improvement, except ocular discomfort.