• Journal of Korean Neurosurgical Society
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• v.41 no.1
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• pp.30-38
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• 2007

Objective : To elucidate the role of aquaporin-4[AQP4] in cerebral edema formation, we studied the expression and subcellular localization of AQP4 in astrocytes after focal cerebral ischemia. Methods : Cerebral ischemia were induced by permanent middle cerebral artery[MCA] occlusion in rats and estimated by the discoloration after triphenyltetrazolium chloride[TTC] immersion. Change of AQP4 expression were evaluated using western blot. Localization of AQP4 was assessed by confocal microscopy and its interaction with ${\alpha}-syntrophin$ was analyzed by immunoprecipitation. Results : After right MCA occlusion, the size of infarct and number of apoptotic cells increased with time. The ratio of GluR1/GluR2 expression also increased during ischemia. The polarized localization of AQP4 in the endfeet of astrocytes contacting with ventricles, vessels and pia mater was changed into the diffuse distribution in cytoplasm. The interactions of AQP4 and Kir with ${\alpha}-syntrophin$, an adaptor of dystrophin complex, were disrupted by cerebral ischemia. Conclusion : The deranged spatial buffering function of astrocytes due to mislocalized AQP4/Kir4.1 channel as well as increased assembly of $Ca^{2+}$ permeable AMPA receptors might contribute to the development of edema formation and the excitotoxic neuronal cell death during ischemia.

• Journal of Haehwa Medicine
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• v.8 no.1
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• pp.425-449
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• 1999

For the evaluation of the effect on SWS, experiments were made on hyperlipidemia induced by hypercholesterol diet, inhibitory reaction to human platelet aggregation, Pulmonary thrombosis induced by collagen and epinephrine, global cerebral ischemia induced by KCN, brain ischemia induced by MCA occlusion, cytotoxicity of PC12 cells induced by amyloid ${\beta}$ protein(25-35), and NO production in RAW cells stimulated by lipopolysaccharide. The results were obtained as follows : 1. In the experiment on hyperlipidemia, the level of serum total cholesterol, phospholipid, and LDL-cholesterol were significantly decreased while the level of triglyceride, VLDL-cholesterol, and HDL-cholesterol had no significant change. 2. In the experiment on inhibitory reaction to platelet aggregation, SWS inhibited platelet aggregation induced by ADP(36.05%), by collagen(20.4%), and by thrombin(0.6%). 3. In the experiment on pulmonary thrombosis induced by collagen and epinephrine, the protective effect was found(37%). 4. In the experiment on global cerebral ischemia, coma duration induced by KCN changed insignificantly. 5. In the experiment on MCA occlusion, the change of neurologic grades on hind limb was significant only after the operation. Besides brain ischemic area and edema ratio were significantly decreased. 6. In the experiment on cytotoxicity of PC 12 cells induced by amyloid ${\beta}$ protein, the significant protective effect was found as concentration increases. 7. In the experiment on NO production in RAW cells stimulated by lipopolysaccharide, NO was significantly decreased. According to the results, it is expected that SWS might be effective on hyperlipidemia and brain damage.

• Biomedical Science Letters
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• v.11 no.3
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• pp.355-363
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• 2005

This study aimed to investigate the cerebroprotective effect of vascular endothelial growth factor (VEGF) on permanent focal cerebral ischemia in Sprague-Dawley rats. Right middle cerebral artery (MCA) was occluded for 6 and 24 hours by an intraluminal monofilament technique. An open cranial window was made on the right parietal bone for determination of continuous changes in regional cerebral blood flow (rCBF) by laser-Doppler flowmetry. The infarct size was morphometrically determined using the 2,3,5-triphenyltetrazolium chloride technique. Brain edema was determined by measuring brain water content. In normal rats, rCBF was significantly increased by intravenous infusion of VEGF for 10 minutes. The VEGF-induced increase in rCBF was significantly inhibited by pretreatment with suramin, a heparin-binding growth factor inhibitor as well as $N^{\omega}-nitro-L-arginine$, a nitric oxide synthase inhibitor. In focal cerebral ischemic rats, the amplitude of decrease in rCBF during ischemic period was significantly less in VEGF-treated group, compared with that in vehicle-treated group. The cerebral infarct size was reduced by VEGF in a dose-dependent manner. The brain edema formation was dose-dependently reduced by VEGF in 24-hour MCA occlusion group but not in 6-hour MCA occlusion group. It is suggested that VEGF not only improves the rCBF during cerebral ischemic period but also reduces the brain edema formation, and thereby exert a protective effect on focal cerebral ischemia in rats.

• Biomedical Science Letters
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• v.11 no.2
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• pp.201-209
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• 2005

This study aimed to investigate the cerebroprotective effect of nociceptin on transient focal cerebral ischemia in Sprague-Dawley rats by determining the changes in regional cerebral blood flow (rCBF) and the infarct size. Right middle cerebral artery (MCA) was occluded for 2 hours, and thereafter was followed by reperfusion by an intraluminal monofilament technique. An open cranial window was made on the right parietal bone for determination of continuous changes in rCBF by laser-Doppler flowmetry. The infarct size was morphometrically determined using the 2,3,5-triphenyltetrazolium chloride technique. In normal rats, nociceptin ($0.01\~100\;nmol/kg$, Lv.) increased rCBF and decreased cerebral arterial resistance in a dose-dependent manner. Systemic arterial blood pressure was little affected by nociceptin at the doses of 0.01 and 0.1nmol/kg, but dose-dependently reduced at the doses of 1 nmol/kg or more. In transient cerebral ischemic rats, nociceptin ($0.01\~0.1$ nmol/kg, i.p.) significantly attenuated the postischemic cerebral hyperemia, and progressively increased rCBF. The improving effect of nociceptin on the postischemic rCBF response was markedly blocked by pretreatment with $[Nphe^1]nociceptin(1-13)NH_2$ (1 nmol/kg, i.p.), a selective nociceptin receptor antagonist, but not by naloxone ($3{\mu}mol/kg$, i.p.), a selective opioid receptor antagonist. The cerebral infarct size was significantly reduced by nociceptin ($0.01\~0.1$ nmol/kg) administered i.p. 5 min after MCA occlusion in transient cerebral ischemia of 2-hour MCA occlusion and 22-hour reperfusiion. It is suggested that nociceptin improves the postischemic cerebral hemodynamics and thereby has a cerebroprotective effect in transient focal cerebral ischemia.

• Annals of Clinical Neurophysiology
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• v.20 no.2
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• pp.79-84
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• 2018

Background: Pulsatility of cerebral arteries and aortic stiffness have been associated with white matter hyperintensities (WMH). We explored which is better correlated with the severity of WMH in a population with acute lacunar infarct. Methods: We included patients with acute small subcortical infarcts who underwent transcranial Doppler (TCD) and brachial ankle pulse wave velocity (baPWV). Exclusion criteria were any stenosis or occlusion on major cerebral arteries on magnetic resonance angiography; poor temporal insonation windows; ankle brachial index < 0.9; and atrial fibrillation. We assessed the performance of the pulsatility index of bilateral middle cerebral arteries (PI-MCA) and baPWV for predicting moderate-to-severe WMH, defined as an Age Related White Matter Changes score > 5, and then sought to find independent predictors using binary logistic regression analysis. Results: Eighty-three patients (56 males, mean age $61.5{\pm}11.4$) participated in the study. Uni-variate analysis showed old age and high PI-MCA were significantly correlated with moderate-to-severe WMH. However, baPWV was not associated with the severity of WMH. Multivariate analysis revealed old age (odds ratio per 1-year increase, 1.068; p = 0.044) and upper tertile of PI-MCA (odds ratio, 5.138; p = 0.049) were independently associated with moderate-to-severe WMH. Receiver-operating characteristics showed PI-MCA differentiated those with and without moderate-to-severe WMH with an area under the curve of 0.719. Conclusions: PI-MCA derived from TCD was better correlated with the severity of WMH than baPWV in a population with lacunar infarction. Pulsatility of cerebral arteries may better predict cerebral small vessel disease than the aortic stiffness index.

• Journal of Yeungnam Medical Science
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• v.36 no.3
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• pp.208-218
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• 2019

Background: The anatomy of middle cerebral artery (MCA) aneurysms has been noted to be unfavorable for endovascular treatment. The purpose of this study was to assess the feasibility and efficacy of coiling for MCA aneurysms. Methods: From January 2004 to December 2015, 72 MCA aneurysms (38 unruptured and 34 ruptured) in 67 patients were treated with coils. Treatment-related complications, clinical outcomes, and immediate and follow-up angiographic outcomes were retrospectively analyzed. Results: Aneurysms were located at the MCA bifurcation (n=60), 1st segment (M1, n=8), and 2nd segment (M2, n=4). Sixty-nine aneurysms (95.8%) were treated by neck remodeling techniques using multi-catheter (n=44), balloon (n=14), stent (n=8), or combination of these (n=3). Only 3 aneurysms were treated by single-catheter technique. Angiographic results were 66 (91.7%) complete, 5 (6.9%) remnant neck, and 1 (1.4%) incomplete occlusion. Procedural complications included aneurysm rupture (n=1), asymptomatic coil migration to the distal vessel (n=1), and acute thromboembolism (n=10) consisting of 8 asymptomatic and 2 symptomatic events. Treatment-related permanent morbidity and mortality rates were 4.5% and 3.0%, respectively. There was no bleeding on clinical follow-up (mean, 29 months; range, 6-108 months). Follow-up angiographic results (mean, 26 months; range, 6-96 months) in patients included 1 major and 3 minor recanalizations. Conclusion: Coiling of MCA aneurysms could be a technically feasible and clinically effective treatment strategy with acceptable angiographic and clinical outcomes. However, the safety and efficacy of this technique as compared to surgical clipping remains to be ascertained.

• The Journal of Korean Medicine
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• v.22 no.1
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• pp.78-89
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• 2001

Objectives : The purpose of this investigation is to evaluate the effects of Woohwangcheongsim-won on reperfusion following MCA occlusion in rats. Methods : To evaluate the effect of Woohwangcheongsim-won on reperfusion following MCA occlusion, the volume of cerebral ischemia and edema were measured and the change of the CAI pyramidal neuron in the hippocampus was investigated by light microscopy. And the changes of several neurotransmitters and enzymes were investigated with the immunohistochemical methods. Results : 1. The volume of the control group, which was ischemic-damaged was 23.6%, and that of the sample group was 13.5%. 2. The voluminalratio of the right/left hemisphere was 116 in the control group, and that of the sample group was 107. 3. The pyramidal cells of CAI area in the control group were greatly damaged. The cells were changed into discontinuous and unsystematic forms, and nuclei, and cytoplasms were shrunk. On the other hand, the cells of the sample group were less damaged. 4. On the immunohistochemical methods, the sensitivities of GABA, NOS, DBH in the control group were increased, and those of synapsin and $eEF-l{\alpha}$ were decreased as compared with the normal group. NOS and DBH which were negative in the normal group showed positive reaction. On the other hand, the sensitivities of GABA, NOS and DBH in the sample group were decreased, but those of NPY, synapsin, CaMKII and $eEF-l{\alpha}$ were increased as compared with the control group. Conclusions : Woohwangcheongsim-won reduced the volume of cerebral ischemia and edema, and minimized the damage of pyramidal cells. The mechanism was related to protein synthesis, such as synapsin, ${\alpha}CaMKII$ and $eEF-l{\alpha}$, which resist neurotoxicity of glutamate receptors.

• Journal of Korean Neurosurgical Society
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• v.44 no.5
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• pp.314-319
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• 2008

Objective: For patients with giant or dissecting aneurysm, multimodal treatment consisting extracranial-intracranial bypass surgery plus clip or coil for parent artery occlusion may be necessary. In this study, the safety and efficacy of multimodal treatment in 15 patients with complex aneurysms were evaluated retrospectively. Methods: From January 1995 to June 2007, the authors treated 15 complex aneurysms that were unable to be clipped or coiled. Among them, nine patitents had unruptured aneurysms and 6 had ruptured aneurysms. Aneurysms were located in the internal cerebral artery (ICA) in 11 patients (4 in the dorsal wall. 4 in the terminal ICA, 1 in the paraclinoid, and 2 in the cavernous ICA), in the middle cerebral artery (MCA) in 2, and in the posterior circulation in two patients Results: Fifteen patients with complex aneurysms were treated with bypass surgery previously. Thirteen patients were treated with external carotid middle cerebral artery (ECA-MCA) anastomosis, and one patient with superficial temporal to posterior cerebral artery (STA-PCA) and another patient with occipital artery to posterior inferior cerebellar artery (OA-PICA) anastomosis. Parent artery occlusion was then performed with a clip in 9 patients, with a coil in 4, with balloon plus coil in one patient. All 15 aneurysms were successfully treated with clip or coil combined with bypass surgery. Follow-up angiograms showed good patency of anastomotic site in 10 out of 11 patients, and perfusion study showed sufficient perfusion in 6 out of 9 patients. Conclusion: These findings indicate that for patients with complex aneurysms, clip or coil for parent vessel occlusion with additive bypass surgery can successfully exclude the aneurysm from the neurovascular circulatory system.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.6
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• pp.665-672
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• 1997

This study aimed to investigate the mechanism of cerebroprotection of platelet-activating factor(PAF) antagonists in transient cerebral ischemia of rat. Right middle cerebral artery(MCA) of Sprague-Dawley rat was occluded for 2 hours using an intraluminal filament technique. After 22 hours of reperfusion, morphometrically detectable infarct was developed in the cortex and striatum identical to the territory of MCA. The infarct size was significantly reduced by PAF antagonists, BN 52021 and CV-6209, as well as an inducible nitric oxide synthase(iNOS) inhibitor aminoguanidine(1 mg/kg, i.p., respectively) administered 5 min after MCA occlusion. PAF antagonists significantly inhibited the enzymatic activities of both myeloperoxidase and iNOS in the cerebral hemisphere ipsilateral to ischemia, whereas aminoguanidine did not inhibit myeloperoxidase activity but significantly inhibited the iNOS activity. These results suggest that PAF antagonists exert a cerebroprotective effect against ischemic brain damage through inhibition of leukocyte infiltration and iNOS activity in the postischemic brain.

• Journal of the Korean neurological association
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• v.36 no.4
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• pp.350-353
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• 2018

Ischemic stroke caused by the cerebral vasculopathy is a rare complication of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. We present a case of recurrent ischemic strokes caused by cerebral vasculopathy in a patient with POEMS syndrome. A 34-year-old man presented with gait disturbance and dizziness. Brain magnetic resonance imaging demonstrated acute ischemic stroke in the middle cerebral artery-anterior cerebral artery (MCA-ACA) border zones of bilateral hemispheres. Repeated angiographic studies showed progressive worsening of the left distal internal carotid artery, ACA, and MCA stenoses, along with sustained steno-occlusion of right MCA.