• Biomolecules & Therapeutics
• /
• 제28권2호
• /
• pp.152-162
• /
• 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.

• Journal of Physiology & Pathology in Korean Medicine
• /
• 제18권2호
• /
• pp.586-595
• /
• 2004

Kamidojuk-San (KDJS) is known to be effective for treating cardiovascular diseases such hypertension, and clinically applied for the treatment of cerebral palsy or stoke patients. Yet, the overall mechanisms underlying its activity at the cellular levels are not known. Using experimental animal system, we investigated whether KDJS has protective effects on cells in cardiovascular and nervous systems. KDJS was found to rescue death of cultured primary neurons induced by AMPA, NMDA and kainate as well as BSO and Fe/sup 2+/ treatments. Moreover, KDJS treatment promoted animal's recovery from coma induced by a lethal dose of KCN treatment, and improved survival in animals exposed to lethal dose of KCN. Neurological examinations further showed that KDJS reduced the time which is required for animals to respond in terms of forelimb and hindlimb movements. To examine its physiological effects on cardiovascular and nervous systems, we induced ischemic injury in hippocampal neurons and cerebral neurons by middle cerebral artery (MCA) occlusion. Histological examination revealed that KDJS significantly protected neurons from ischemic damage. Thus, the present data suggest that KDJS may play an important role in protecting cells of cardiovascular and nervous systems from external noxious stimulations.

• Annals of Clinical Neurophysiology
• /
• 제1권2호
• /
• pp.99-105
• /
• 1999

Background and Objectives : The Motor evoked potentials (MEP) study may be useful in the evaluation of the degree of impairment in the motor nervous system and in the determination of the prognosis. The purpose of this study is to evaluate the status of central nervous system in acute and subacute state of cerebral ischemia by comparing the changes of MEP in the initial and follow-up study. Methods : Twenty patients with hemiparesis caused by ischemic stroke were recruited for this study. We tested MEP within 7 days and followed-up after 14 days after symptom onset. The cerebral motor cortex area, cervical area for upper extremity and lumbar area for lower extremity were stimulated by transmagnetic stimulator. The central motor conduction time(CMCT) was measured with the difference in MEP caused by stimulating the vertical area and spinal area. The CMCT of hemiparetic patients were classified into three groups-normal, delayed, and no evoked MEP groups. Results : The CMCT in hemiparetic side of acute ischemic stroke patients were singnificantly delayed (P < 0.05) compared with the control group. The CMCT of hemiparetic side in the follow-up study showed no sinificantly difference in comparison to the control group. The prognosis of motor improvement was better in the groups of delayed MEP than the groups of no evoked MEP. Conclusion : The CMCT of hemiparetic and contralateral sides were delayed in acute ischemic stroke, compared with control group and were returned to normal boundaries in subacute state. But in the most cases with no MEP response in the initial study, also showed no MEP response in the follow-up study. The recovery occurred in the subacute state in cases with mild hemiparesis, whereas recovery did not occur in the subacute stage in case with severe hemiparesis.

• Preventive Nutrition and Food Science
• /
• 제16권3호
• /
• pp.217-223
• /
• 2011

Ischemic stroke constitutes about 80% of all stroke incidences. It is characterized by brain cell death in a region where cerebral arteries supplying blood are occluded. Under these ischemic conditions, apoptosis is responsible for the cell death, at least in part. Goat's-beard (Aruncus dioicus var. kamtschaticus) is a perennial plant that grows naturally in the alpine regions of Korea. In the present study, we first determined whether water extract of goat's-beard (HY1646) and some of its fractions prepared by partitioning with organic solvents could improve the viability of human hepatocellular carcinoma cells (HepG2) cultured under hypoxic condition by blocking apoptotic pathways. Based on the in vitro findings, we subsequently investigated whether HY1646 and the ethyl acetate fraction (EA) selected from cell culture-based screening could attenuate brain injury in a rat middle cerebral artery occlusion (MCAO) model of ischemia (2 hr), followed by 22 hours of reperfusion. The cell number was sustained close to that initially plated in the presence of HY1646 even after 24 hr of cell culture under hypoxic condition (3% $O_2$), at which time the cell number reached almost zero in the absence of HY1646. This improvement in cell viability was attributed to the delay in apoptosis, identified by the formation of DNA ladder in gel electrophoresis. Of fractions soluble in hexane, ethyl acetate (EA) and butanol, EA was chosen for the animal experiments because EA demonstrated the best cell viability at the lowest concentration (10 ${\mu}g$/mL). HY1646 (200 mg/kg) and EA (10 and 20 mg/kg) significantly reduced infarct size, an index of brain injury, by 16.6, 40.0 and 61.0%, respectively, as assessed by 2,3,5-triphenyl tetrazolium chloride staining. The findings suggest that prophylactic intake of goat's beard might be beneficial for preventing ischemic stroke.

• Journal of Ginseng Research
• /
• 제46권2호
• /
• pp.275-282
• /
• 2022

Background: Stroke is a neurological disorder characterized by brain tissue damage following a decrease in oxygen supply to brain due to blocked blood vessels. Reportedly, 80% of all stroke cases are classified as cerebral infarction, and the incidence rate of this condition increases with age. Herein, we compared the efficacies of Korean White ginseng (WG) and Korean Red Ginseng (RG) extracts (WGex and RGex, respectively) in an ischemic stroke mouse model and confirmed the underlying mechanisms of action. Methods: Mice were orally administered WGex or RGex 1 h before middle cerebral artery occlusion (MCAO), for 2 h; the size of the infarct area was measured 24 h after MCAO induction. Then, the neurological deficit score was evaluated and the efficacies of the two extracts were compared. Finally, their mechanisms of action were confirmed with tissue staining and protein quantification. Results: In the MCAO-induced ischemic stroke mouse model, WGex and RGex showed neuroprotective effects in the cortical region, with RGex demonstrating superior efficacy than WGex. Ginsenoside Rg1, a representative indicator substance, was not involved in mediating the effects of WGex and RGex. Conclusion: WGex and RGex could alleviate the brain injury caused by ischemia/reperfusion, with RGex showing a more potent effect. At 1,000 mg/kg body weight, only RGex reduced cerebral infarction and edema, and both anti-inflammatory and anti-apoptotic pathways were involved in mediating these effects.

• Journal of the Korean Society of Radiology
• /
• 제82권1호
• /
• pp.261-266
• /
• 2021

Ischemic stroke is one of the manifestations of reversible cerebral vasoconstriction syndrome (RCVS). Many precipitants and associated disorders of RCVS have been suggested. However, few case reports have indicated an association between anemia and RCVS. Here, we report a case of a 66-year-old female with severe iron deficiency anemia (IDA), who presented with ischemic stroke and cerebral vasoconstriction, which gradually improved with conservative treatment. High-resolution vessel wall magnetic resonance imaging findings and reversibility suggested the possibility of RCVS. In patients with RCVS and ischemic stroke, IDA should be considered. Prompt management should be delivered to prevent disease progression and recurrence.

• Herbal Formula Science
• /
• 제13권1호
• /
• pp.49-69
• /
• 2005

This Study was designed to investigate the effect of Sunkihwalhyul -Tang extract(SHT) on the change of cerebral hemodynamics [regional cerebral blood flow(rCBF), pial arterial diameter(PAD) and mean arterial blood pressure(MABP)] in normal and cerebral ischemic rats, and further to determine the mechanisms of action of SHT on hemodynamics. In addition, this study was designed to investigate whether SHT inhibits lactate dehydrog enase(LDH) activity in neuronal cells and cytokines production in serum of cerebral ischemic rats. The results were as follows 1. SHT significantly increased rCBF and PAD in a dose-dependent manner, but MABP was not changed by injecting SHT. These results suggest that SHT significantly increases rCBF by dilating PAD. 2. The SHT-induced increase in rCBF was significantly inhibited by pretreatment with indomethacin(IDN, 1 mg/kg, i.p.), an inhibitor of cyclooxygenase and methylene blue(MTB, $10{\mu}g/kg$, i.p.), an inhibitor of guanylate cyclase. 3. The SHT-induced dilation in PAD was significantly inhibited by pretreatment with IDN and MTB. 4. The SHT-induced some increase in MABP was significantly increased by pretreatment with IDN. These results suggest that the mechanism of action of SBT is mediated by guanylate cyclase. 5. Both rCBF and PAD were significantly and stably increased by SHT(10 mg/kg, i.p.) during the period of cerebral reperfusion, which contrasted with the findings of rapid and marked increase in control group. 6. SBH significantly inhibited LDH activity in neuronal cells. These results suggest that SHT prevents the neuronal death. 7. In cytokine production in the senlm drawn from femoral artery 1 hr after middlecerebral arterial occlusion, sample group showed significantly decreased production of IL-1$\beta$ production, decreased production TNF-$\alpha$ and increased Production of IL-10 compared with control group. 8. In cytokine production in the serum drawn femoral artery 1 hr after reperfusion, sample group showed significantly decreased production of IL-1$\beta$ and TNF-$\alpha$ as wellas significantly increased production of IL10 compared with control group. These results suggest that SHT mediated by guanylate cyclase has inhibitive effect on the brain damage by inhibiting LDH activity, IL-1$\beta$ and TNF-$\alpha$ production, and by accelerating IL-10 production. The present author thinks that SHT has an anti-ischemic effects through the improvement of cerebral hemodynamics and inhibitive enects on the brain damage.

• Journal of Acupuncture Research
• /
• 제21권4호
• /
• pp.207-215
• /
• 2004

Objective : In order to prove the effect of Hirudin Herbal-acupuncture this experimental studies were performed by using rats that had neuronal damage due to the Middle Cerebral Artery Occulsion(MCAO). Methods : Microdialysis probes were implanted into the coordinate of striatum of anesthetized rats which consist of sham-operated 8 rats, MCAO-operated 8 rats and Hirudin Herbal-acupuncture administrated 8 rats before MCAO operating. The Hirudin Herbal-acupuncture(0.5mg/kg) was administrated to rats 30 minutes before having an operation causing the MCAO. The surgical excision lead the cross resected brain to the acute ischemic state. The brain was sliced in 2mm thickness and stained with cresyl violet buffer for the measurement of cerebral infarcted area and volume. Results : Based on the result of the tissue inspection for the cerebral ischemic cell, Hirudin Herbal-acupuncture significantly protect neurocytes. Conclusion : We suggest Hirudin Herbal-acupuncture produces protective effects against the neuronal damage induced by MCAO. Therefore, Hirudin Herbal-acupuncture may prevent delayed neuronal death(DND) in selectively vulnerable focal areas of the brain effectively.

• Journal of Acupuncture Research
• /
• 제21권1호
• /
• pp.33-50
• /
• 2004

Objective: The aim of this study was to investigate anti-ischemic effect of LR1 HT8 Reduction in Acupuncture Methods: I designed to investigate whether LR1 HT8 Reduction in Acupuncture affects cerebral hemodynamics [regional cerebral blood flow(rCBF), pial arterial diameter(PAD), mean arterial blood pressure(MABP)] in normal rats and to make manifest whether LR1 HT8 Reduction in Acupuncture is mediated by cyclooxygenase or guanylate cyclase. The changes of rCBF and MABP were determinated by laser-doppler flowmetry(LDF), and the change of PAD was de terminated by video microscope and width analyzer. Results: The results were as follows; 1. LR1 Reduction in Acupuncture was increased rCBF and PAD, but decreased MABP. 2. HT8 Reduction in Acupuncture was significantly increased rCBF, but decreased MABP, and increased PAD. 3. LR1 HT8 Reduction in Acupuncture was significantly increased rCBF, PAD, but decreased MABP after withdrawing of the needle. This results suggest that LR1 HT8 Reduction in Acupuncture increased significantly rCBF by dilating PAD. 4. Pretreatment with indomethacin(1mg/kg, i,v.) was significantly inhibited LR1 HT8 Reduction in Acupuncture induced increase of rCBF and PAD, but increased LR1 HT8 Reduction in Acupuncture induced decrease of MABP after withdrawing of the needle. 5. Pretreatment with methylene blue($10{\mu}g/kg$, i,v.) was decreased LR1 HT8 Reduction in Acupuncture induced increase of rCBF and PAD, but accelerated LR1 HT8 Reduction in Acupuncture induced decrease of MABP. Conclusions: I suggest that LR1 HT8 Reduction in Acupuncture has an anti-ischemic effect through the improvement of cerebral hemodynamics, and the mechanism is mediated by cyclooxygenase.

• The Korean Journal of Nuclear Medicine
• /
• 제23권2호
• /
• pp.149-154
• /
• 1989

Transient ischemic attacks (TIAs) is a syndrome resulting from brain ischemia lasting less than 24 hours. The mechanisms of TIAs may be similar to those of cerebral embolism and thrombosis, and thus TIAs may be followed by cerebral infarction. Despite the availability of CT scanning, the diagnosis and management of TIAs continue to be difficult. Recently SPECT has been advocated as a diagnostic imaging modality. We performed Tc-99m-HMPAO regional cerebral blood flow (rCBF) SPECT in 24 patients with the clinical diagnosis of TIAs to assess its ability to detect early changes of rCBF, and determine the diagnostic value. Ten men and fourteen women with an average of 51 years (range; 27-74 years) were included. All but 8 patients had normal brain CT prior to SPECT. The two patients had moderate degree of brain atrophy and the 6 patients nonspecific calcifications. Eighteen of the 24 patients had abnormal Tc-99m-HMPAO rCBF SPECT. Fifteen had unilateral involvement and the other three had bilateral involvements. Seventy-five percents of the defects were found in the left cerebral hemisphere. According to the distribution of the lesions (total number: 34 lesions), fourteen were in the parietal, eight in the temporal, and the remainders were elsewhere. Tc-99m-HMPAO rCBF SPECT is sensitive in detecting rCBF abnormalities in patients with TIAs, and represent the most accurate diagnostic tool available in the diagnosis of TIAs.