• The Journal of Korean Medicine
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• v.22 no.1
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• pp.10-21
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• 2001

Objective : This study was performed to investigate the protective effect of Stephania tetrandra(ST) against ischemic brain damage after a middle cerebral artery(MCA) occlusion. The effect was evaluated using histological tests, neurobehavioral tests, and biochemical tests. Methods : Rats(Sprague-Dawley) were divided into four groups : sham operated group, MCA occluded group, post MCA occlusion Stephania tetrandra administrated (7.6mg/l00g) group, and normal group. The MCA was occluded by intraluminal method. Stephania tetrandra was administrated orally twice at 1 and 4 hours after MCA occlusion. The neurobehavioral test was performed at 3, 6, 9 and 24 hours after MCA occlusion by posture reflex test and swimming behavioral test. All groups were sacrificed then. The brain tissues were stained with 2% triphenyl tetrazolium chloride(TTC) or 1 % cresyl violet solution, to examine infarct size, volume and cell number. Tumor necrosis $factor-{\alpha}$ level was measured from sera using Enzyme-Linked Immunoabsorbent Assay(ELISA). The mRNA expression level of inflammatory cytokines and related receptor type I and II, $IL-1{\beta}$, IL-6, and IL-10 6hours after MCA occlusion were also studied by reverse transcriptase polymerase chain reaction(RTPCR). Results : The results showed that : Stephania tetrandra (1) reduced infarct size and total infarct volume by 52.2% compared to the control group; (2) attenuated significantly in neuronal death, which was shown by a decrease in cell number(P<0.01) and size(P<0.01) in the boundary area of the infarction; (3) significantly reduced serum $TNF-{\alpha}$ level, and increased the mRNA level of IL-10 in the cortex region(P<0.01). However, there was no significant effect on motor deficit in swimming behavioral test. Conclusions : In conclusion, Stephania tetrandra has protective effects against ischemic brain damage at the early stage of ischemia.

• Journal of Industrial Convergence
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• v.17 no.4
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• pp.39-43
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• 2019

Mouse embryonic stem cell could show an substitutional materials of cells of neuron differentiation, positively increasing their effectiveness in the treatment of nervous symptom. We examined that mouse embryonic stem cells (mESCs) can be induced to undergo neuronal differentiation. After neuronal induction, the phenotype of mESCs changed towards neuronal morphology and mESCs were injected into the lateral ventricle of the experimental animal brain. Transplanted cells migrated to various parts of the brain and ischemic brain injury by middle cerebral artery occlusion (MCAO) increased their migration to the injured cortex. Intracerebral grafting of mESCs mostly improve sensory and motor nervous system of neurological injury in focal cerebral rats.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.5
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• pp.275-280
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• 2008

A brief ischemic insult induces significant protection against subsequent massive ischemic events. The molecular mechanisms known as preconditioning (PC)-induced ischemic tolerance are not completely understood. We investigated whether kinetic changes of cyclooxygenase (COX)-2 during reperfusion time-periods after PC were related to ischemic tolerance. Rats were given PC by occlusion of middle cerebral artery (MCAO) for 10 min and sacrificed after the indicated time-periods of reperfusion (1, 2, 4, 8, 12, 18 or 24 h). In PC-treated rats, focal ischemia was induced by occlusion of MCA for 24 h and brain infarct volume was then studied to determine whether different reperfusion time influenced the damage. We report that the most significant protection against focal ischemia was obtained in rats with 8 h reperfusion after PC. Administration of indomethacin (10 mg/kg, oral) or rofecoxib (5 mg/kg, oral) 48 h prior to PC counteracted the effect of PC. Immunohistochemical analysis showed that COX-2 and HO-l protein were induced in PC-treated rat brain, which was significantly inhibited by rofecoxib. Taken together, we concluded that the kinetic changes of COX-2 expression during the reperfusion period after PC might be partly responsible for ischemic tolerance.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.4
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• pp.281-296
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• 2021

The beneficial effects of hypoxic preconditioning are abolished in the diabetes. The present study was designed to investigate the protective effects and mechanisms of repeated episodes of whole body hypoxic preconditioning (WBHP) in db/db mice. The protective effects of preconditioning were explored on diabetes-induced vascular dysfunction, cognitive impairment and ischemia-reperfusion (IR)-induced increase in myocardial injury. Sixteen-week old db/db (diabetic) and C57BL/6 (non-diabetic) mice were employed. There was a significant impairment in cognitive function (Morris Water Maze test), endothelial function (acetylcholine-induced relaxation in aortic rings) and a significant increase in IR-induced heart injury (Langendorff apparatus) in db/db mice. WBHP stimulus was given by exposing mice to four alternate cycles of low (8%) and normal air O₂ for 10 min each. A single episode of WBHP failed to produce protection; however, two and three episodes of WBHP significantly produced beneficial effects on the heart, brain and blood vessels. There was a significant increase in the levels of brain-derived neurotrophic factor (BDNF) and nitric oxide (NO) in response to 3 episodes of WBHP. Moreover, pretreatment with the BDNF receptor, TrkB antagonist (ANA-12) and NO synthase inhibitor (L-NAME) attenuated the protective effects imparted by three episodes of WBHP. These pharmacological agents abolished WBHP-induced restoration of p-GSK-3β/GSK-3β ratio and Nrf2 levels in IR-subjected hearts. It is concluded that repeated episodes of WHBP attenuate cognitive impairment, vascular dysfunction and enhancement in IR-induced myocardial injury in diabetic mice be due to increase in NO and BDNF levels that may eventually activate GSK-3β and Nrf2 signaling pathway to confer protection.

• Journal of Trauma and Injury
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• v.26 no.3
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• pp.226-228
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• 2013

Elderly patients with acute subdural hematomas have higher mortality and lower functional recovery rates compared with those of other head-injured patients. Early and widely surgical decompression and active intensive care represent the best way to assist these patients. However, abrupt decompression of the hematoma can lead to brain disruption and secondary ischemia in the brain surrounding the craniectomy site. Acute brain swelling and brain extrusion, which take place shortly after decompression, can lead to a catastrophic situation during the operation due to the impossibility of appropriate closure of the dura and scalp. To avoid the deleterious consequences of disruption of brain tissue, we have adopted multiple fenestrations of the dura in a mesh-like fashion and gradual release of subdural clots through the small dural openings that are left open. This is especially important in cases in which there are massive amount of subdural hematomas with small parenchymal lesion and severe midline shifts in elderly patients. Further clinical experiences should be conducted in a more selected series patients to estimate the impact of this technique on morbidity and mortality rates.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.2
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• pp.467-475
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• 2003

This studt was investigated to prove the effect of GMYM on the brain damage. The results were as follows; 1. GMYM showed significantly inhibitory effect on LDH release by NMDA. AMPA and Kinate. 2. GMYM showed significantly inhibitory effect on LDH release by BSO and Fe2+. 3. GMYM decreased coma duration time in a infatal dose of KCN and showed 30% of survival rate in a fatal dose. 4. GMYM showed improvement of forelimb and hindlimb test after MCA occulusion in neurological exemination. 5. GMYM decreased ischemic area and edema incited by the MCA blood flow block. These results indicate that GMYM can be used in the brain damage sujected to brain ischemia. Further study will be needed about the functional mechanism and etc.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.2
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• pp.145-152
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• 2017

Remote ischemic preconditioning (RIPC) is an intrinsic phenomenon whereby 3~4 consecutive ischemia-reperfusion cycles to a remote tissue (non-cardiac) increases the tolerance of the myocardium to sustained ischemia-reperfusion induced injury. Remote ischemic preconditioning induces the local release of chemical mediators which activate the sensory nerve endings to convey signals to the brain. The latter consequently stimulates the efferent nerve endings innervating the myocardium to induce cardioprotection. Indeed, RIPC-induced cardioprotective effects are reliant on the presence of intact neuronal pathways, which has been confirmed using nerve resection of nerves including femoral nerve, vagus nerve, and sciatic nerve. The involvement of neurogenic signaling has been further substantiated using various pharmacological modulators including hexamethonium and trimetaphan. The present review focuses on the potential involvement of neurogenic pathways in mediating remote ischemic preconditioning-induced cardioprotection.

• Journal of Life Science
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• v.32 no.7
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• pp.550-566
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• 2022

Stroke is among the leading causes of death and long-term physical and cognitive disabilities worldwide, affecting an estimated 15 million people annually. The pathophysiological process of stroke is complicated by multiple and coordinated events. The breakdown of the blood-brain barrier (BBB) in people with stroke can significantly contribute to the development of ischemic brain injury. Therefore, BBB disruption is recognized as a hallmark of stroke; thus, it is important to develop novel therapeutic strategies that can protect against BBB dysfunction in ischemic stroke. Traditional medicines are composed of natural products, which represent a promising source of new ingredients for the development of conventional medicines. Indeed, several studies have shown the effectiveness of Korean medicine on stroke, highlighting the value of Korean medicinal treatment for ischemic stroke. This review summarizes the current information and underlying mechanisms regarding the ameliorating effects of the formula, decoction, herbs, and active components of traditional Korean medicine on cerebral ischemia-induced BBB disruption. These traditional medicines were shown to have protective effects on the BBB in many cellular and animal ischemia models of stroke, and experiments in various animal species, such as mice and rats. In addition, they showed brain-protective effects by protecting the BBB through the regulation of tight junction proteins and matrix metalloproteinase-9, reducing edema, neuroinflammation, and neuronal cell death. We hope that this review will help promote further investigation into the neuroprotective effects of traditional Korean medicines and stimulate the performance of clinical trials on Korean herbal medicine-derived drugs in patients with stroke.

• Korean Journal of Veterinary Research
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• v.41 no.4
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• pp.467-475
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• 2001

Cardiac arrest, hypoxia, shock or seizure has been known to induce cerebral ischemia. This study was designed to investigate the effect of ischemia on hippocampal pyramidal layer induced by transient bilateral occlusion of the common carotid arteries. Mature Mongolian gerbils were sacrificed at days 2, 4, and 7 after carotid occlusion for 10 minutes. Sham-operated gerbils of control group were subjected to the same protocol except for carotid occlusion. During operation for ischemia, body temperature was maintained $37{\pm}0.5^{\circ}C$ in all gerbils. Paraffin-embedded brain tissue blocks were cut into coronal slices and stained with H-E stain or immunostain by TUNEL method. Neurons with the oval and prominent nucleus and without the eosinophilic cytoplasm in the subfield of hippocamapal pyramidal layer were calculated as to be viable neurons. Their chromatins were condensed or clumped. Their nuclei appeared multiangular or irregularly shrinked. The width of the pyramidal layer was reduced due to the loss of nuclei. At day 2 after reperfusion, some neurons in the CA1 subfield were slightly eosinophilic. But most neurons in the CA2 subfield were strongly eosinophilic. At day 4 day, most neurons in the CA1 subfield were severely damaged and at day 7 day, only a few survived neurons were observed. Survived neurons per longitudinal 1mm sector in the CA1, CA2, CA3, and CA4 subfields of pyramidal layer were investigated. At day 2, the mean numbers of pyramidal neurons in CA1, CA2, CA3, and CA4 subfiedls were 104.5/mm (54.3%), 51.0/mm (33.8%), 105.5/mm (85.6%), and 124.3/mm (93.5%) compared to the nonischemic control group, respectively. At day 4, the mean numbers of pyramidal neurons in CA1, CA2, CA3, and CA4 subfields were 3.2/mm (1.7%), 51.5/mm(34.2%), 95.3/mm (77.4%), and 112.5/mm (84.6%), respectively. At day 7, the mean numbers of pyramidal neurons in CA1, CA2, CA3, and CA4 subfiedls were 0.8/mm (0.4%), 5.7/mm(3.8%), 9.8/mm (8.0%), and 5.0/mm (3.7%), respectively. The mean numbers of apoptotic positive neurons in the CA1 subfield at day 2, 4, and 7 after reperfusion were 67.8/mm, 153.2/mm and 123.7/mm, respectively. These results suggest that the transient cerebral ischemia cause severe damages in most neurons at day 7 and that the prosminent apoptotic positive neurons in hippocampal pyramidal layer are the delayed neuronal death induced by ischemia.

• Korean Journal of Acupuncture
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• v.19 no.2
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• pp.63-78
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• 2002

Kupunggibodan(KU), Gamisamul-tang(GA) and Whangryunhaedok-tang(WH) are clinically the most popular prescriptions as an herbal medicine in the treatment of ischemia. In order to compare and evaluate their protective effects on the ischema-induced cognitive deficits by middle cerebral artery occlusion (MCAO), we examined its ability to improve ischemia-induced cell loss and impairements of learning and memory in the Morris water maze and eight-arm radial arm maze. Focal cerebral ischemia produced a marked cell loss, decrease in acetylcholinesterase(AchE) reactivity in the hippocampus, and learning and memory deficits in two behavioral tasks. Pretreatment with WH (100 mg/kg, p.o.) produced a substantial increase in acquisition in the Morris water maze. Pretreatment with KU increased the perfomance of the resention test in the Morris water maze. WH, KU and GA caused a significant improvement in choice accuracy in radial arm maze test. WH was superior to KU and GA in perfomance of the radial arm maze test. Consistent with behavioral data, staining with cresyl violet showed that pretreatments with WH, but not KU and GA significantly recovered the ischemia-induced cell loss in the hippcampal CA1 area. In addition, pretreatments with WH and KU recovered the ischemia-induced reduction of AchE reactivity in the hippocampal CA1 area. These results demonstrated that KU, GA and WH have protective effects against ischimea-induced learning and memory impairments and that the efficacy was the order of WH>KU>GA in tratment of ischemia induced memory deficits. The present studies provide an evidence of KU, GA and WH as putative treatment of vascular dementia. Supported by a fund from the Ministry of Health and Welfare(HMP-00-OO-04-0004), and the Brain Korea 21 Project from Korean Ministry of Education, Korea.