• Journal of Acupuncture Research
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• v.25 no.1
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• pp.1-14
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• 2008

Objectives : Delayed neuronal death(DND) of pyramidal neuronsin the CA1 regions of the hippocampus has been extensively studied following global brain ischemia, whereas little is known about DND in this highly vulnerable brain region after focal brain ischemia. The aim of the present study was to investigate the effect of Gastrodiae Elata(GA) pharmacopuncture on hippocampal neuronal apoptosis in rats with focal brain ischemic injury. Materials and methods : The neuroprotective effects of water extracts of GA were investigated in middle cerebral artery occlusion(MCAo) of Sprague-Dawley(SD) rats. Seventy-five healthy SD ratswere randomly divided into five groups following MCAo : control group with focal ischemia, saline injection group, pharmacopuncture group GA-1($0.0007mg/m{\ell}/g$), pharmacopuncture group GA-2($0.00035mg/m{\ell}/g$), pharmacopuncture group GA-3($0.00014mg/m{\ell}/g$). Results : The intensity of mGluR5 increased in the GA-1 group. The intensity of Bax and the Bax/Bcl-2 ratio decreased in the GA-1 group. The intensity of Bcl-2 increased in all the GA groups. The density of neurons stained by Cresyl violet and ChAT increased in the GA-1 group. Conclusions : Our study suggests that GA pharmacopuncture at $GB_{20}$ showed anti-apoptotic and neuroprotective effects on cholinergic neuronsin focal cerebral ischemia caused by stroke in SD rats.

• Biomolecules & Therapeutics
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• v.21 no.6
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• pp.454-461
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• 2013

The neuroprotective effects of a butanol fraction of white rose petal extract (WRPE-BF) were investigated in a middle cerebral artery occlusion (MCAO) model. Seven week-old male rats were orally administered WRPE-BF for 2 weeks and subjected to MCAO for 2 h, followed by reperfusion. Twenty-four h later, MCAO-induced behavioral dysfunctions were markedly improved in a dose-dependent manner by pretreatment with WRPE-BF. Moreover, higher dose of WRPE-BF not only decreased infarction area but also effectively reduced astrogliosis. The expression of inducible nitric oxide synthase, cyclooxygenase-2, and glial fibrillary acidic protein in MCAO model were markedly inhibited by WRPE-BF treatment. Notably, WRPE-BF decreased nitricoxide and malondialdehyde levels in the striatum and subventricular zone of stroke-challenged brains. These data suggested that WRPE-BF may exert its neuroprotective effects via anti-oxidative and anti-inflammatory activities against ischemia-reperfusion brain injury and could be a good candidate as a therapeutic target for ischemic stroke.

• The Korea Journal of Herbology
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• v.26 no.4
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• pp.67-74
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• 2011

Objectives : The purpose of the study is to determine the neuroprotective effects of the water extract of Angelicae Acutilobae Radix(AA) on ischemia reperfusion-induced apoptosis in SK-N-SH human brain neuronal cells. Methods: SK-N-SH cells were treated with different concentrations of AA water extract (0.1, 0.2, 0.5 and 1.0 mg/ml) for 2 hr and then stimulated with Dulbecco's phosphate-buffered saline containing CI-DPBS: 3mM sodium azide and 10 mM 2-deoxy-D-glucose for 45 min, reperfused with growth medium, and incubated for 24 h. Cell viability was determined by WST-1 assay, and ATP/ADP levels were measured by ADP/ATP ratio assay kit. The levels of caspase-3 protein were determined by Western blot and apoptotic body was observed by Hoechst 33258 staining. Results : AA extract significantly inhibited decreasing the cell viability in ischemia-induced SK-N-SH cells. AA also increased the ratio of ADP/ATP in ischemia-induced neuronal cells and decreased the expression levels of apoptotic protein, caspase-3 and apoptotic DNA damage. Conclusions : Our results suggest that AA extract has a neuroprotective property via suppressing the apoptosis and increasing the energy levels in neuronal cells, suggesting that AA extract may has a therapeutic potential in the treatment of ischemic brain injury.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.1
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• pp.47-52
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• 1999

Blood flow restoration to ischemic zone of the heart is essential to salvage of ischemic tissue. However, there is a large body of evidence documenting that the reperfusion can induce reperfusion injury like reperfusion-induced malignant arrhythmias. In the present study, employing a cat model of regional cardiac ischemia, we examined if reperfusion rendered in a gradual fashion could lower the incidence of reperfusion-induced ventricular fibrillation (VF), which usually precipitated within a few to several tens of seconds after abrupt reperfusion. The experiments were conducted with male mongrel cats (n=46, 2.5-5 kg). The animals in the control and 30 MIN groups were subjected to an episode of 20- and 30-min left anterior descending coronary artery occlusion, respectively, followed by abrupt reperfusion. The animals in 5 G and 10 G groups received gradual reperfusion over a 5- and 10-min period, respectively, following a 20-min occlusion. The proportion of animals that exhibited VF during the reperfusion phase was 11/15 in the control, 7/10 in the 30 MIN, 5/10 in the 5 G and 2/11 in the 10 G groups. The incidence of VF in the 10 G group was significantly lower than that in the control or 30 MIN group subjected to abrupt reperfusion. These results suggest that the gradual reperfusion is a useful procedure against reperfusion-induced VF.

• Laboraroty Animal Research
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• v.34 no.4
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• pp.195-202
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• 2018

Hyperglycemia is one of the major risk factors for stroke. Hyperglycemia can lead to a more extensive infarct volume, aggravate neuronal damage after cerebral ischemia. ${\alpha}$-Synuclein is especially abundant in neuronal tissue, where it underlies the etiopathology of several neurodegenerative diseases. This study investigated whether hyperglycemic conditions regulate the expression of ${\alpha}$-synuclein in middle cerebral artery occlusion (MCAO)-induced cerebral ischemic injury. Male Sprague-Dawley rats were treated with streptozotocin (40 mg/kg) via intraperitoneal injection to induce hyperglycemic conditions. MCAO were performed four weeks after streptozotocin injection to induce focal cerebral ischemia, and cerebral cortex tissues were obtained 24 hours after MCAO. We confirmed that MCAO induced neurological functional deficits and cerebral infarction, and these changes were more extensive in diabetic animals compared to non-diabetic animals. Moreover, we identified a decrease in ${\alpha}$-synuclein after MCAO injury. Diabetic animals showed a more serious decrease in ${\alpha}$-synuclein than non-diabetic animals. Western blot and reverse-transcription PCR analyses confirmed more extensive decreases in ${\alpha}$-synuclein expression in MCAO-injured animals with diabetic condition than these of non-diabetic animals. It is accepted that ${\alpha}$-synuclein modulates neuronal cell death and exerts a neuroprotective effect. Thus, the results of this study suggest that hyperglycemic conditions cause more serious brain damage in ischemic brain injuries by decreasing ${\alpha}$-synuclein expression.

• The Korea Journal of Herbology
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• v.28 no.2
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• pp.45-53
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• 2013

Objectives : The purpose of the study is to determine the neuroprotective effects of the water and 80% EtOH extract of some herbal medicine plant on ischemia reperfusion-induced cell death in SK-N-SH human brain neuronal cells. Methods : SK-N-SH cells were treated with 3mM sodium azide and 10 mM 2-deoxy-D-glucose for 45 min, ptior to the addition of different concentrations of herbal medicine plant extract (0, 10, 25, 50, 100, 250, 500, 1000 ${\mu}g/ml$) for 2 hr and then reperfused with growth medium, incubated for 24 h. Cell viability was determined by WST-1 assay, and ATP/ADP levels were measured by ADP/ATP ratio assay kit. Results : Herbal medicine plant extract significantly inhibited decreasing the cell viability in ischemia-induced SK-N-SH cells. Also increased the ratio of ADP/ATP in ischemia-induced neuronal cells. Conclusions : Our results suggest that herbal medicine plant extract has a neuroprotective property via increasing the energy levels in neuronal cells, suggesting that extract may has a therapeutic potential in the treatment of ischemic brain injury. The exact component and mechanism remains for the future study.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.62-62
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• 2003

It is now convincing that free radical generation is involved in the pathophy siological mechanisms of ischemic stroke, particularly in ischemia-reperfusion injury. The present study, therefore, examined neuroprotective effect of aloesin isolated from Aloe vera, which was known to have antioxidative activity, in a rat model of transient focal cerebral ischemia. Transient focal cerebral ischemia was induced by occlusion of middle cerebral artery for 2 hr with a silicone-coated 4-0 nylon monofilament in male Sprague-Dawley rats under isoflurane anesthesia Aloesin (1, 3, 10, 30 and 50 mg/kg/injection) was administered intravenously 3 times at 0.5, 2 and 4 hr after onset of ischemia. Neurological score was measured 24 hr after onset of ischemia immediately before sacrifice. Seven serial coronal slices of the brain were stained with 2,3,5-triphenyltetrazolium chloride and infarct size was measured using a computerized image analyzer. Treatment with the close of 1 or 50 mg/kg did not significantly reduce infarct volume compared with the saline vehicle-treated control group. However, treatments with the closes of 3 and 10 mg/kg significantly reduced both infarct volume and edema by approximately 47% compared with the control group, producing remarkable behavioral recovery effect. Treatment with the close of 30 mg/kg also significantly reduced infarct volume to a lesser extent by approximately 33% compared with the control group, but produced similar degree of behavioral recovery effect. In addition, general pharmacological studies showed that aloesin was a quite safe compound. The results suggest that aloesin can serve as a lead chemical for the development of neuroprotective agents by providing neuroprotection against focal ischemic neuronal injury.

• Korean Journal of Head & Neck Oncology
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• v.9 no.1
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• pp.3-9
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• 1993

The benficial effects for perfusion in the preservation of free flaps have been controversial in the clinical and experimental field until now. This study was undertaken to observe the effect of UW solution. a recently developed. high molecular weight. organ perfusion solution. for protection of ischemic injury in normothermic free myocutaneous flaps. Forty rabbits were used in this sutdy. A 1x2x1cm sized gastrocnemius myocutaneous flap based on the feeding vessel from common femoral artery was made. The author set up the ischemic time for 12 hours in these flaps. The flap was washed out with normal saline(control grop, n=10), urokinase(comparative group I, n=10), UW solution before ischemic time(comparative group II, n=10) and UW solution before ischemic time and pentoxifylline before reperfusion(comparative group III, n=10). Afterthen, reperfusion was made for 12 hours. After this procedure, we checked the degree of ischemia and necrosis of myocutaneous flap by gross finding, electrical stimulation test of muscle, triphenyltetrazolium chloride staining and wet/dry weight ratio. The degree of necrosis of comparative group II and III were lesser than control and urokinase group in gross finding(p<0.05). In the electrical stimulation test of muscle, there was no statistical difference between control($1.76{\pm}1.01$) and urokinase($2.36{\pm}\1.02$) group however the muscular power of comparative group II($3.54{\pm}0.93$) and III($3.49{\pm}1.37gm/mm^2$) demonstrated significantly higher than control group(p<0.05). The ischemic findings were found in seven cases of control group and three cases of urokinase group but there were no ischemic findings in comparative group II and III in TIC stain(p<0.05). In the wet/dry weight ratio of flaps in order to evaluate the tissue edema. there was no statistical difference between control($4.55{\pm}0.29$) and III($3.75{\pm}0.48$) were scored significantly lesser than control and urokinase group (p<0.05). These results suggest that perfusion washout with UW solution improves the viability of normothermic free myocutaneous flap by inhibition of cellular swelling.

• Clinical and Experimental Pediatrics
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• v.51 no.2
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• pp.170-180
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• 2008

Purpose : Some antibiotics were known to exert neuroprotective effects in the animal model of hypoxic-ischemic (H-I) brain injury, but the mechanism is still unclear. A recent study reported that geneticin (G418), an aminoglycoside antibiotic, increased survival of human breast cancer cells by suppressing apoptosis. We investigated the neuroprotective effects of systemically administrated geneticin via anti-apoptosis following the H-I brain injury Methods : Seven-day-old Sprague-Dawley rat pups were subjected to unilateral (left) common carotid artery occlusion followed by 2.5 hours of hypoxic exposure and the cortical cell culture of rat brain was done under a hypoxic incubator. Apoptosis was measured in the injured hemispheres 7 days after H-I insult and in the injured cells from hypoxic chamber using morphologic analysis by Terminal dUTP Nick-end Labeling(TUNEL) assay and immunohistochemistry for caspase-3, and cytologic analysis by western blot and real time PCR for bax, bcl-2, and caspase-3. Results : The gross appearance and hematoxylin and eosin stain revealed increased brain volume in the geneticin-treated animal model of perinatal H-I brain injury. The TUNEL assay revealed decreased apoptotic cells after administration of geneticin in the cell culture model of anoxia. Immunohistochemistry showed decreased caspase-3 expression in geneticin-treated cortical cell culture. Western blot and real-time PCR showed decreased caspase-3 expression and decreased ratio of Bax/Bcl-2 expression in geneticin-treated animal model. Conclusion : Geneticin appears to exert a neuroprotective effect against perinatal H-I brain injury at least via anti-apoptosis. However, more experiments are needed in order to demonstrate the usefulness of geneticin as a preventive and rescue treatment for H-I brain injuries of neonatal brain.

• Journal of Chest Surgery
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• v.28 no.11
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• pp.963-966
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• 1995

Ischemia reperfusion injury occurs in various diseases. The role of oxygen free radicals in IR injury of the lung has been spotlighted and many studies have been performed. In this study, we tried to prepare a stable rat lung model for IR injury, focusing on surrounding conditions as hilar stripped left lung, clamped left pulmonary artery and bronchus,and declamped after determined period was passed, and right main pulmonary aretery was clamped. Arterial blood gas analyes were performed at 1, 10, 20, 30, minutes after reperfusion. Before clamping, PaO2 was 95 to 120 mmHg in all animals. There were six groups; Group I : temperature 15o C, and 120 minutes clamping, Group II: 20 oC, and 120 minutes clamping, Group III : 25 oC, and 120 minutes clamping, Group IV : 15oC, 90 minutes clamping, Group V : 20 oC, 90 minutes clamping,Group VI: 20 oC, 75 minutes clamping. Each groups contained 10 Sprague Dayley rats. The humidity was maintained 100 % as circulation imerged isotonic Hartmann`s solution of the pleural cavity. In group IV, V, and VI, PaO2 decreased significantly in all animals immediately after reperfusion, but 43 % survived till 10 minutes after reperfusion, it was 74.0$\pm$5.7, 73.3$\pm$10.8,and 88.2$\pm$17.7 mmHg. Pulmonary edema was observed histologically in 2/10 animals in group IV, 6/10 in group V , 3/10 in group VI, 9/10 in group I, and the other lungs showed all edema. We established a stable model by setting ischemic time,and temperature, between 75 to 90 minutes,15 to 20o C, and isotemperature Hartmann`s solution immersion of the pleural cavity.