• Biomolecules & Therapeutics
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• v.32 no.3
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• pp.319-328
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• 2024

Lysophosphatidic acid receptor 1 (LPA₁) plays a critical role in brain injury following a transient brain ischemic stroke. However, its role in permanent brain ischemic stroke remains unknown. To address this, we investigated whether LPA₁ could contribute to brain injury of mice challenged by permanent middle cerebral artery occlusion (pMCAO). A selective LPA₁ antagonist (AM152) was used as a pharmacological tool for this investigation. When AM152 was given to pMCAO-challenged mice one hour after occlusion, pMCAO-induced brain damage such as brain infarction, functional neurological deficits, apoptosis, and blood-brain barrier disruption was significantly attenuated. Histological analyses demonstrated that AM152 administration attenuated microglial activation and proliferation in injured brain after pMCAO challenge. AM152 administration also attenuated abnormal neuroinflammatory responses by decreasing expression levels of pro-inflammatory cytokines while increasing expression levels of anti-inflammatory cytokines in the injured brain. As underlying effector pathways, NF-κB, MAPKs (ERK1/2, p38, and JNKs), and PI3K/Akt were found to be involved in LPA₁-dependent pathogenesis. Collectively, these results demonstrate that LPA₁ can contribute to brain injury by permanent ischemic stroke, along with relevant pathogenic events in an injured brain.

• The Journal of Internal Korean Medicine
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• v.28 no.4
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• pp.741-750
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• 2007

Objective : This study investigated the relationship between diet and lifestyle and Sasang constitution (SC) in acute stroke patients. Methods : From October 2005 to March 2007, 379 acute stroke patients were included. Patients were hospitalized within 14 days after the onset of stroke at DongGuk University International Hospital, Kyungwon University In-cheon Oriental Medical Hospital or Department Cardiovascular and Neurologic Diseases (stroke center), Kyung Hee University Oriental hospital. We assessed the type of SC of acute stroke patients by Questionnaire for Sasang Constitution Classification II (QSCC II). We investigated general characteristics, stroke types, dietary preferences (meat, sea food, fast food, alcohol drinking, coffee and green tea drinking) and lifestyle (smoking, exercise) according to SC. Results : This study showed that out of the total patients, the proportion of So-yang to Tae-eum to So-eumwas equal to 2.6 to 2 to 1. Of note, this study showed a higher proportion in age of So-eum & weight of Tae-eum. The ratio of cerebral hemorrhage to cerebral infarction was 1 to 9. SVO, LAA, SUE are the 3 types of cerebral infarction classified by TOAST; SVO ranked the highest while SUE ranked the lowest in all constitutions. There were no significant differences between So-yang and Tae-eum in the aspect of the preference for meat, but the majority of So-eum displayed high preferences for seafood. In the aspect of alcohol drinking and smoking history, So-yang recorded significantly bigger proportion while So-eum & Tae-eum patients represented a bigger proportion than So-yangin the aspect of no exercise habits. Conclusion : According to the result above, we could observe the general disposition of various characteristic distributions according to SC of acute stroke patients. Also, we could observe a relationship between diet and lifestyle and Sasang constitution (SC) in acute stroke patients. Further studies will be needed to better understand the relationship between diet and lifestyle and Sasang constitution (SC) in acute stroke patients.

• The Journal of Internal Korean Medicine
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• v.29 no.3
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• pp.629-640
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• 2008

Objective : The purpose of this study was to investigate the neuroprotective effect of Jukryuk on 4-vessel occlusion(4-VO) and middle cerebral artery (MCA) ischemia. Method : After administration of Jukryuk, we compared the Jukryuk-treated group, the control, and the sham groups, in view of several points as follows 1) We evaluated the damage characterized by coagulative cell change of pyramidal neurons and pronounced gliosis in each group 2) We counted the number of normal pyramidal shapes after ischemia in each group 3) Immunohistochemistry (cyclooxygenase-2) 4) In focal ischemic injury model, we measured the volume of ischemic area Results : In this experiment, the effect of Jukryuk was determined to be protecting neuron cell shape, reducing the number of neuron cells damaged by ischemia and the volume of the ischemic area. In immunohistochemistry, Jukryuk reduced cyclooxygenase-2 expression Conclusions : According to this study, Jukryuk can protect neuron cells from injury by cerebrovascular ischemia.

• Biomolecules & Therapeutics
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• v.28 no.2
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• pp.152-162
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• 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 Korean Neurosurgical Society
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• v.39 no.2
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• pp.130-135
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• 2006

Objective : After ischemic stroke, partial recovery of function frequently occurs and may depend on the plasticity of axonal connections. Here, we examine whether blockade of the Nogo/NogoReceptor[NgR] pathway might enhance axonal sprouting and thereby recovery after focal brain infarction. Methods : Adult male Sprague Dawley rats weighing $250{\sim}350g$ were used. Left middle cerebral artery occlusion[MCAO] was induced with a intraluminal filament. An osmotic mini pump [Alzet 2ML4, Alza Scientific Products, Palo Alto, CA] for the infusion of NgR-Ecto[310]-Fc to block Nogo/NgR pathway was implanted 1 week after cerebral ischemia. Prior to induction of ischemia, all animals received training in the staircase and rotarod test. Two weeks after biotin dextran amine injection, animals were perfused transcardially with PBS, followed by 4% paraformadehyde/PBS solution. Brain and cervical spinal cord were dissected. Eight coronal sections spaced at 1mm intervals throughout the forebrain of each animal with cresyl violet acetate for determination of infarction size. Images of each section were digitized and the infarct area per section was measured with image analysis software. Results : Histological examination at 11 weeks post-MCAO demonstrates reproducible stroke lesions and no significant difference in the size of the stroke between the NgR[310]Ecto-Fc protein treated group and the control group. Behavioral recovery is significantly better and more rapid in the NgR-Ecto[310]-Fe treated group. Blockade of NgR enhances axonal sprouting from the uninjured cerebral cortex and improves the return of motor task performance. Conclusion : Pharmacological interruption of NgR allows a greater degree of axonal plasticity in response this is associated with improved functional recovery of complicated motor tasks.

• Journal of Yeungnam Medical Science
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• v.11 no.1
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• pp.63-71
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• 1994

The purpose of this study was to evaluate the effect of stroke on hypothalamic-pituitary axis using dexamethasone suppression test. The effects were evaluated according to age, sex, type, size, and lesion site of stroke. These tests were performed in 62 patients with stroke(cerebral infarction, 42 cases : intracerebral hemorrage, 20 cases) and 21 disabled controlled patients without intracranial diseases at Yeungnam University Hospital from June 1992 to June 1993. The results summarized as follows. 1. Cerebral infarction showed significantly higher frequency of DST non-suppression in stroke patients than control(p<0.05). 2. Patients with left hemisphere stroke showed more frequent abnormal neuroendocrine test results(p<0.01) 3. Patients with large infarction revealed strongly non-suppressed DST results(p<0.01). 4. Sinificantly higher basal cortisol level in patients with cerebral infarction was noted(p<0.01). 5. There are no statistical significance between DST results and sex, age, motor impairment, type of cerebral infarction.

• The Journal of Korean Medicine
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• v.26 no.1 s.61
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• pp.115-122
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• 2005

Background and objective: Gastrodiae Rhizoma (GR), the rhizoma of Gastrodia elata BL., is one of the popular drugs to treat headache, dizziness, blackout, numbness of limbs, hemiplegia, facial paralysis, dysphrasia, and infantile convulsions. It has been reported that it provides an antihypertensive effect and lowers cerebrovascular resistance in animal experiments. However, there has been no data about these effects with human subjects. In this study, the author examined the effect of Gastrodiae water extracts on blood pressure and cerebrovascular reactivity in human subjects. Methods: We selected 16 normal volunteers, who were divided into 2 groups: Gastrodiae extract administration group and placebo (creamy powder) group. Using transcranial Doppler ultrasound, we monitored changes of mean flow velocity and breath-holding induced CO2 reactivity of middle cerebral artery in both groups. Mean blood pressure, heart rate and PETCO2 were measured using Compact Anesthesia Monitor. In both groups, all evaluation was performed during basal condition, and repeated at 30, 60, and 90 min after administration. Results: Gastrodiae extract decreased CO2 reactivity after administration, reaching the lowest level at 90 minutes $(-29.1\%\;vs.\;basal\;level)$, which showed significant difference compared with the placebo group (p = 0.004). In the placebo group, the pulse rates tended to decrease over time (at 90 minute, $-5.2\%$ vs. basal level) while in the Gastrodiae group the values showed nearly no change, which showed significant difference between both groups (p = 0.036). However, the changes of mean blood pressure and mean flow velocity did not show significant difference between both groups. Conclusion : This study demonstrated that Gastrodiae extract significantly decreased breath-holding induced CO2 reactivity. This result suggests that the clinical effect of Gastrodiae extract might be caused by increasing cerebral blood flow via dilation of cerebral resistant vessels instead of antihypertensive effect.

• The Journal of Korean Medicine
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• v.27 no.3 s.67
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• pp.38-50
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• 2006

Objectives: The aim of this study was to evaluate the effects of Korean ginseng (KG), Korean red ginseng (KRG) and fermented Korean red ginseng (FKRG) extracts on cerebral hemodynamics and to compare distinction of each extract. Methods: Ten healthy male volunteers $(26.0{\pm}1.8yrs)$ participated in the study according to double-blind and cross-over protocols. Each volunteer was blindly administered 500mg of KG, KRG, FKRG extract or placebo (Dextrin). Blinded researchers measured changes of hyperventilation-induced cerebrovascular reactivity (CVR), mean blood flow velocity (MBFV) of middle cerebral arteries (MCAs) and corrected blood flow velocity at $P_{ETCO2}=40mmHg$ (CV40) using transcranial Doppler ultrasound (DWL Co., Germany). Researchers also observed changes of mean blood pressure (MBP), pulse rate (PR) and expiratory $CO_2$ using S/5 Collector (Datex-Ohmeda Co., Finland). The evaluation was performed at basal condition, and repeated at 1, 2, 3, 4 and 5 hours after administration. Results: MBFV and CV40 in the KRG group tended to rise at I hour after administration, while those of the FKRG group tended to rise at 2 hours after administration. CVR increased significantly after 1 hour in the KRG group (p=0.009) and after 2 hours in the FKRG group (p=0.035), respectively. The KG group showed increasing tendency at 4 hours after administration. No group showed significant difference from the placebo in changes of MBP and PR. Conclusions: It is suggested that KG, KRG and FKRG extracts have effects of enhancing CVR and thus of increasing cerebral blood flow in human subjects.

• Physical Therapy Korea
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• v.13 no.3
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• pp.57-66
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• 2006

Ischemic stroke results from a transient or permanent reduction in cerebral blood flow that is restricted to the territory of a major brain artery. Thus, this study was performed to examine (1) the effects of swimming exercise on the improvement of muscle atrophy, and (2) exercise and HSP 70 expression in an ischemic stroke model induced by middle cerebral artery occlusion. The results of this study were as follows: One week after ischemic stroke was induced, changes appeared in the muscle weight of the gastrocnemius muscle due to muscle atrophy in the affected side. Group II showed statistically significant difference from group III eight weeks after ischemic stroke was induced. (p<.05). One week and eight weeks after ischemic stroke was induced there was significant decrease in the relative muscle weight of the gastrocnemius muscle in each group except Group IV, while there was statistically significant increase in group II eight weeks after ischemic stroke was induced, compared to group III (p<.05). For neurologic exercise behavior tests, Group II generally had the highest score, compared to other groups. In immunohistochemical observations, Group II showed a decrease in HSP 70. The above results suggest that swimming exercise improved muscle atrophy, changed the HSP 70 expression of ischemic stroke in rats, and contributed to the improvement of exercise function.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.13 no.3
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• pp.1153-1160
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• 2012

This study was intended to implement ankle joint dorsi flexion training against ankle muscule strength weakening that erodes stroke patients' gait performance to examine the effect of the training on stroke patients' plantar pressure and gait ability. In this study, 36 stroke patients diagnosed with stroke due to cerebral infarction or cerebral hemorrhage were divided to measure 10MWS which are stroke patients' gait variables maximum plantar pressure by area of the sole by collecting data using an F-scan system during gait. Given these results of the study, compared to other training groups, the ankle muscule strength reinforcing training group showed statistically significant increases of maximum plantar pressure in the great toe, the toe and the first metatasal areas too and thus it can be said that this training increases forward thrust during stroke patients' foot end taking off and positively affects stroke patients' ability to perform gait.