• The Korean Journal of Pharmacology
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• v.29 no.1
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• pp.9-22
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• 1993

To evaluate the protective effects of calcium antagonists, oxygen radical scavengers and excitatory amino acid (EAA) antagonist on the ischemic brain damage, we induced in vitro ischemic condition (namely, lack of oxygen and glucose) to rat hippocampal slices. And the degree of ischemic damage was determined by assaying changes in biochemical parameters such as ATP content and lactate ralease, MDA production in the presence or absence of the various drugs. During experimental ischemia for up to 60 min, ATP content was decreased and the amount of lactate release was markedly increased time-dependently. By changing the reaction medium which contained oxygen and glucose those biochemical parameters were recovered. But the recovery was not complete in this experimental condition. In the same ischemic conditions verapamil and vitamine E prevented the decrease of ATP content and the increase of lactate release from the slices. And verapamil and diltiazem decreased MDA release to the reaction medium. Superoxide dismutase (SOD) and MK-801 (as EAA receptor antagonist) protected the decrease of ATP content and reduced MDA release in 20 min ischemic condition, but glutathione affected ATP content and lactate release at the same condition. When oxygen and glucose were resupplied for 20 min after ischemic condition, verapamil showed the protective effect on the changes of ATP content and lactate release, and vitamine E decreased lactate release (at 20 min ischemia) and MDA release (at 60 min ischemia). These results showed that calcium antagonist and vitamine E protect the ischemic biochemical changes from rat hippocampal slices and calcium antagonist is more potent than vitamine E to protect the ischemical brain damege.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.3
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• pp.257-263
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• 2009

This study aimed to investigate whether selective serotonin reuptake inhibitors (SSRIs) attenuate brain injury and facilitate recovery following photothrombotic cortical ischemia in mice. Male ICR mice were anesthetized and systemically administered Rose Bengal. Permanent focal ischemia was induced in the medial frontal and somatosensory cortices by irradiating the skull with cold light laser. The animals were treated with fluoxetine or sertraline once a day for 14 d starting 1 h after ischemic insult. Treatment with fluoxetine and sertraline significantly reduced the infarct size. The Evans blue extravasation indices of the fluoxetine- and sertraline-treated groups were significantly lower than that of the vehicle group. Treatment with fluoxetine and sertraline shifted the lower limit of the mean arterial blood pressure for cerebral blood flow autoregulation toward normal, and significantly increased the expression of heme oxygenase-1 (HO-1) and hypoxia-inducible factor-1 ${\alpha}$ (HIF-1 ${\alpha}$) proteins in the ischemic region. These results suggest that SSRIs, such as fluoxetine and sertraline, facilitate recovery following photothrombotic cortical ischemia via enhancement of HO-1 and HIF-1 ${\alpha}$ proteins expression, thereby providing a benefit in therapy of cerebral ischemia.

• The Journal of Internal Korean Medicine
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• v.31 no.2
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• pp.380-387
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• 2010

The ischemic penumbra represents part of the hypoperfused region associated with focal brain ischemia. A practical approach is to define this region as that portion of the ischemic territory that can potentially be salvaged by timely intervention. For the prevention and treatment of ischemic stroke, antithrombotic therapy is prescribed. But medication of antiplatelet agent is only validated as prevention effect. Cheonghyulgangki-tang has been used for cerebral apoplexy, hypertension, etc. In this case report, an acute ischemic stroke patient was treated with an antiplatelet agent named Plavix and Cheonghyulgangki-tang and remarkable reduction of ischemic portion in the brain CT was observed. The result of this case suggests that oriental medical therapy could be a safe and effective intervention in acute ischemic stroke.

• Biomedical Science Letters
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• v.21 no.2
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• pp.92-102
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• 2015

This work aimed to study whether rice bran extract fermented with Lactobacillus plantarum (LW) promotes functional recovery and reduces cognitive impairment after ischemic brain injury. Ischemic brain injury was induced by middle cerebral artery occlusion (MCAO) in rats. Four groups were studied, namely the (1) sham, (2) vehicle, (3) donepezil, and (4) LW groups. Animals were injected with LW once a day for 7 days after middle cerebral artery occlusion. LW group showed significantly improved neurological function as compared to the vehicle group, as well as enhanced learning and memory in the Morris water maze. The LW group showed the greatest functional recovery. Moreover, the LW group showed an enhanced more survival cells anti-apoptotic effect in the cortex and neural cell densities in the hippocampal DG and CA1. In addition, this group showed enhanced expression of neurotrophic factors, antioxidant genes, and the acetylcholine receptor gene, as well as synaptophysin (SYP), Fox-3 (NeuN), doublecortin (DCX), and choline acetyltransferase (ChAT) proteins. Our findings indicate that LW treatment showed the largest effects in functional recovery and cognitive improvement after ischemic brain injury through stimulation of the acetylcholine receptor, antioxidant genes, neurotrophic factors, and expression of NeuN, SYP, DCX, and ChAT.

• Reproductive and Developmental Biology
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• v.35 no.2
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• pp.167-174
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• 2011

Acute ischemic stroke results from sudden decrease or loss of blood supply to an area of the brain, resulting in a coinciding loss of neurological function. The antioxidant action of melatonin is an important mechanism among its known effects to protective activity during ischemic/reperfusion injury. The focus of this research, therapeutic efficacy of melatonin on recovery of neurological function following long term treatment in ischemic brain injured rats. Male Sprague-Dawley rats (n=40; 8 weeks old) were divided into the control group, and MCAo groups (Vehicle, MT7 : MCAo+ melatonin injection at 7:00, MT19 : MCAo+melatonin injection at 19:00, and MT7,19 : MCAo+melatonin injection at 7:00 and 19:00). Rat body weight and neurological function were measured every week for 8 weeks. After 8 weeks, the rats were anesthetized with a mixture of zoletil (40 mg/kg) and xylazine (10 mg/kg) and sacrificed for further analysis. Tissues were then collected for RNA isolation from brain tissue. Also, brain tissues were analyzed by histological procedures. We elucidated that melatonin was not toxic in vital organs. MT7,19 was the most rapidly got back to mild symptom on test of neurological parameter. Also, exogenous melatonin induces both the down-regulation of detrimental genes, such as NOSs and the up-regulation of beneficial gene, including BDNF during long term administration after focal cerebral ischemia. Melatonin treatment reduced the loss of primary motor cortex. Therefore, we suggest that melatonin could be act as prophylactic as well as therapeutic agent for neurorehabilitative intervention.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.3
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• pp.760-764
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• 2005

This research was performed to investigate protective effect of Sophora Subprostrata fractions against focal ischemic brain damage after middle cerebral artery(MCA) occlusion. Rats were divided into six groups: MCA-occluded group(Control); each administered groups with Sophora Subprostrata total phase(Total), Sophora Subprostrata Aqueous phase (Aqueous), Sophora Subprostrata BuOH phase(BuOH), and Sophora Subprostrata Alkaloid phase(Alkaloid) after MCA-occlusion; sham-operated group(Sham). The right MCA was occluded by A poly-L-lysine coated 4-0 nylon suture thread through the internal carotid artery permanently. Sophora Subprostrata and fractions were administered orally(5mg/ml) for 7 days after MCA-occlusion. The behavior of ischemic rats were examined at 24 hours, 3, 5 and 7 days after MCA-occlusion from the views of 4 different aspects: posture & balance tests(4 subtests), reflex tests(6 subtests), muscle-tone tests(3 subtests), and foot-fault test. The results showed that 1) in muscle tone test, Sophora Subprostrata total phase only increased reduced muscle tone function from 3 to 7 days, 2) in reflex test, Sophora Subprostrata total and Aqueous phase increased fast recovery from 24 hours and 3 days, 3) in posture & balance test, Sophora Subprostrata total and Aqueous phase increased fast recovery from 24 hours, and Sophora Subprostrata BuOH and Alkaloid phase increased posture & balance function from 3 days, but 4) in motor function test, Sophora Subprostrata did not show effective recovery compared with control group. In conclusion, Sophora Subprostrata has protective effects against brain damage at the early stage of focal cerebral ischemia. Sophora Subprostrata total and Aqueous phase produced more pronounced protective effect against focal ischemic brain damage.

• The Journal of Korean Medicine
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• v.21 no.2
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• pp.68-78
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• 2000

Objective : This research was performed to investigate protective effects of Sophora subprostrata, against ischemic brain damage after a middle cerebral artery(MCA) occlusion. The effect was estimated using histological test, neurobehavioural test, and biochemical test. Methods : Rats(Sprague-Dawley) were divided into four groups: Sham operated group, MCA occluded group, Sophora subprostrata administrated group after MCA occlusion, and Normal group. The MCA was occluded by intraluminal method. Sophora subprostrata was administrated orally twice(l and 4 hours) after middle cerebral artery occlusion. The neurobeavioural test was performed at 3 hours, 6 hours, 9 hours and 24 hours after the surgery by posture reflex test and swimming behavioural test. All groups were sacrificed at 24 hours after the surgery. The brain tissue was stained with 2% triphenyl tetrazolium chioride(TTC) or 1 % cresyl violet solution, to examine effect of Sophora subprostrata on ischemic brain tissue. The blood samples were obtained from the heart of rats. Tumor necrosis factor-a level was measured from sera using Enzyme-Linked Immunoabsorbent Assay(ELISA). Results : The results showed that (1) Sophora subprostrata reduced infarct size and total infarct volume by 54.8% compared to the control group, (2) that neuronal death, which was shown by decrease in cell number and size, was attenuated significantly in the boundary area of the infarction, (3) that serum $TNF-{\alpha}$ㆍlevel was reduced significantly, and finally, there was significant recovery of motor deficit at 3 hours after MCA occluded by Swimming behavioural test. Conclusions :In conclusion, Sophora subprostrata has protective effects against ischemic brain damage at the early stage of ischemia.

• The Journal of Internal Korean Medicine
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• v.21 no.4
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• pp.535-542
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• 2000

The water extracts of Samul-tang(SMT) has been used for treatment of ischemic brain damage in Oriental traditional medicine. However, little is known about the mechanism by which the water extracts of SMT rescues brain cells from ischemic damages. To elucidate the protective mechanism on ischemic induced cytotoxicity, I investigate the regulation of LPS and PMA induced iNOS expression in C6 glial cells. LPS and PMA treatment for 72 h in C6 glial cells markedly induce nitric oxide(NO), but treatment of the cells with the water extracts of SMT decrease. dose dependently nitrite formation. In addition, LPS and PMA treatment for 72 h induce severe cell death and LDH release in C6 glial cells. However treatment of the cells with the water extracts of SMT dose not induce significant changes compare to control cells. Furthermore, the protective effects of the water extracts of SMT is mimicked by treatment of $N^{G}MMA$, a specific inhibitor of NOS. LPS and PMA induced iNOS activation in C6 glial cells cause chromosomal condensation and fragmentation of nuclei by caspase activation. The treatment of the cells with the water extracts of SMT may suppress apoptosis via caspase inhibition by regulation of iNOS expression. Taken together, I suggest that the protective effects of the water extracts of SMT against ischemic brain damages may be mediated by regulation of iNOS during ischemic condition.

• Journal of Korean Biological Nursing Science
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• v.23 no.3
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• pp.217-226
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• 2021

Purpose: The aim of this study was to investigate the risk factors for brain reperfusion injury in ischemic stroke patients and to analyze the clinical outcomes. Methods: A retrospective study was conducted in 168 patients who underwent mechanical thrombectomy. The data were analyzed using descriptive statistics, t-test, Mann-Whitney U test, Chi-Square test, Fisher's exact test, and logistic regression with IBM SPSS/WIN 24.0. Results: Brain reperfusion injury occurred in 67 patients (39.9%) with a low favored outcome (𝛘²=6.01, p=.014). On multivariable analysis, blood urea nitrogen (Odds ratio [OR]=1.14, 95% Confidence interval [CI]=1.06-1.23), aphasia (OR=6.16, CI=1.62-23.40), anosognosia (OR=4.84, CI=1.13-20.79), presence of both aphasia and anosognosia (OR=7.33, CI=1.20-44.60), and time required to achieve targeted blood pressure (OR=1.00, CI=1.00-1.00) were identified as risk factors for brain reperfusion injury. A statistically significant difference was detected in clinical outcomes, including hemorrhagic transformation (𝛘²=6.32, p=.012), intensive care unit length of stay (Z=-2.08, p=.038), National Institute of Health Stroke scale score at discharge (Z=-3.14, p=.002), and modified Rankin Scale score at discharge (Z=-2.93, p=.003). Conclusion: This study identified the risk factors and presented the clinical outcomes of brain reperfusion injury. It is necessary to consider these risk factors for evaluating the patients and to establish nursing interventions and strategies.

• Physical Therapy Korea
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• v.14 no.1
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• pp.1-10
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• 2007

This study was designed to examine the effects of electroacupuncture and treadmill exercise on the improvement of muscle atrophy and Brain-Derived Neurotrophic Factor (BDNF) expression in an ischemic stroke model induced by middle cerebral artery occlusion. This study selected 120 Sprangue-Dawley rats, divided them into six groups, and assigned 5 rats to each group. Experiments were conducted for 1, 3 days and 1, 8 weeks, respectively. In each group, changes in weight of muscle and relative muscle of tibialis anterior muscle, histologic observations, and BDNF expression were observed and analyzed. For the changes in muscle weight of unaffected and affected sides of tibialis anterior, muscle atrophy was expressed in an affected side 3 days after ischemic stroke was induced. There was a statistically significant difference in Group VI 1 and 8 weeks after ischemic stroke was induced, compared to Group II (p<.05). For the changes in relative muscle weight of unaffected and affected sides of tibial anterior muscle, there was significant decrease in each group 3 days after ischemic stroke was induced, compared to Group I, while there was a statistically significant increase in Group VI 1 week after ischemic stroke was induced, compared to Group II (p<.05). For neurologic exercise behavior test, Group VI generally had the highest score, compared to other groups. The results of the behavior test suggests that 8 weeks after ischemic stroke was induced, Group VI improved in degeneration and inflammation of muscle fiber and decreased in destruction of nerve cells and cerebral infarction, thus indicating a similar state of muscle fiber and brain tissue in Group I. In immunohistochemical observations, Group 1 week showed increase in BDNF. Based on these results, electroacupuncture and treadmill exercise may improve muscle atrophy and change in BDNF expression of ischemic stroke rats and contribute to the improvement of exercise function.