• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.3
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• pp.594-601
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• 2002

The current study was carried out to evaluate neuroprotective effects of Citri Pericarpium after transient global ischemia in gerbils. Male Mongolian gerbils weighing 60-80g were anesthetized with 2% isoflurane mixed with 30% oxygen and 70 % nitrogen. Bilateral common carotid arteries were occluded for 5 minute with microaneurysm dips. On 3 or 7 days after ischemic surgery, the gerbils were sacrificed. The brain were removed, embedded in paraffin and sectioned at 8㎛-thickness. Gerbils that received ischemic insult for 5 min showed extensive neuronal damage in the hippocampal CA1 region, and the number of viable neuronal cell was 51.0±2.5/mm, 32.2% of normal group at 7 days after ischemic surgery. In animals that underwent the extract of Citri Pericarpium treatment, the number of viable neuronal cell were significantly better preserved at 110.58±3.58/mm, 72.0% of normal group than those of ischemic group (P<0.01). In the immunohistochemistry of Bax and Bcl-2, the Citri Pericarpium treated group down-regulated the expression of Bax protein at 72hr after transient global ischemia. In contrast, Bcl-2 protein level was not changed. The appearance in TUNEL assay is similar to the pattern of Bax protein. The water extract of Citri Pericarpium significantly reduced the number of TUNEL-positive CA1 pyramidal neurons at 72hr. The results suggest that Citri Pericarpium has potential neuroprotective effects in the transient global ischemia and the increase in the ratio of Bcl-2 to Bax may contribute to the anti-apoptotic effect of Citri Pericarpium.

• Molecules and Cells
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• v.45 no.4
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• pp.216-230
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• 2022

SERTA domain-containing protein 1 (Sertad1) is upregulated in the models of DNA damage and Alzheimer's disease, contributing to neuronal death. However, the role and mechanism of Sertad1 in ischemic/hypoxic neurological injury remain unclear. In the present study, our results showed that the expression of Sertad1 was upregulated in a mouse middle cerebral artery occlusion and reperfusion model and in HT22 cells after oxygen-glucose deprivation/reoxygenation (OGD/R). Sertad1 knockdown significantly ameliorated ischemia-induced brain infarct volume, neurological deficits and neuronal apoptosis. In addition, it significantly ameliorated the OGD/R-induced inhibition of cell viability and apoptotic cell death in HT22 cells. Sertad1 knockdown significantly inhibited the ischemic/hypoxic-induced expression of p-Rb, B-Myb, and Bim in vivo and in vitro. However, Sertad1 overexpression significantly exacerbated the OGD/R-induced inhibition of cell viability and apoptotic cell death and p-Rb, B-Myb, and Bim expression in HT22 cells. In further studies, we demonstrated that Sertad1 directly binds to CDK4 and the CDK4 inhibitor ON123300 restores the effects of Sertad1 overexpression on OGD/R-induced apoptotic cell death and p-Rb, B-Myb, and Bim expression in HT22 cells. These results suggested that Sertad1 contributed to ischemic/hypoxic neurological injury by activating the CDK4/p-Rb pathway.

• Clinical and Experimental Pediatrics
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• v.51 no.10
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• pp.1102-1111
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• 2008

Purpose : Resveratrol, extracted from red wine and grapes, has an anti-cancer effect, an antiinflammatory effect, and an antioxidative effect mainly in heart disease and also has neuroprotective effects in the adult animal model. No studies for neuroprotective effects during the neonatal periods have been reported. Therefore, we studied the neuroprotective effect of resveratrol on hypoxic-ischemic brain damage in neonatal rats via anti-apoptosis. Methods : Embryonic cortical neuronal cell culture of rat brain was performed using pregnant Sprague-Dawley (SD) rats at 18 days of gestation (E18) for the in vitro approach. We injured the cells with hypoxia and administered resveratrol (1, 10, and $30{\mu}g/mL$) to the cells at 30 minutes before hypoxic insults. In addition, unilateral carotid artery ligation with hypoxia was induced in 7-day-old neonatal rats for the in vivo approach. We injected resveratrol (30 mg/kg) intraperitoneally into animal models. Real-time PCR and Western blotting were performed to identify the neuroprotective effects of resveratrol through anti-apoptosis. Results : In the in vitro approach of hypoxia, the expression of Bax, caspase-3, and the ratio of Bax/Bcl-2, indicators of the level of apoptosis, were significantly increased in the hypoxia group compared to the normoxia group. In the case of the resveratrol-treated group, expression was significantly decreased compared to the hypoxia group. And the results in the in vivo approach were the same as in the in vitro approach. Conclusion : The present study demonstrates that resveratrol plays neuroprotective role in hypoxic-ischemic brain damage during neonatal periods through the mechanism of anti-apoptosis.

• Journal of Korean Neurosurgical Society
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• v.29 no.9
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• pp.1179-1183
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• 2000

Objective : The treatment of malignant posttraumatic brain swelling remains a frustrating endeavor for neurosurgeon. Mortality and morbidity rates remain high depite advances in medical treatment of increased intracranial pressure. If conventional therapy fails in patients suffering from intracranial hypertension, there is only small number of second-tier option left including decompressive craniectomy. The role of decompressive craniectomy in posttraumatic brain swelling remains controversial. We assessed the efficacy and indications of decompressive craniectomy. Methods : The authors performed decompressive bifrontotemporal craniectomy in 22 patients with malignant posttraumatic brain swelling. Epidural pressure monotoring was performed in all patients. The clnical data and surgical outcomes were reviewed retrospectively. Result : The favorable outcome(GOS score 4-5) was 59%(13 of 22 patients), whereas the mortality rate was 32% (7 of 22 patients). Two patients(9%) remained in severely disabled state. Increased rate of favorable outcome was seen in the patients who had 8 or more of GCS score at admission and exhibited B wave in ICP monitoring and who showed steady state or slow deterioration in clinical course. Conclusion : If conservative therapy fails, decompressive bifrontotemporal craniectomy should be considered in the management of malignant posttraumatic brain swelling before irreversible ischemic brain damage occur.

• The Korean Journal of Physiology and Pharmacology
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• v.8 no.4
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• pp.187-194
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• 2004

Middle cerebral artery occlusion (MCAO) results in cell death by activation of complex signal pathways for cell death and survival. Hypothermia is a robust neuroprotectant, and its effect has often been attributed to various mechanisms, but it is not yet clear. Upstream from the cell death promoters and executioners are several enzymes that may activate several transcription factors involved in cell death and survival. In this study, we immunohistochemically examined the phosphorylation of mitogen-activated protein kinase, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 kinase during early period of the ischemic injury, following 2 hours (h) of transient MCAO. Increased phosphorylation of ERK and p38 was observed in the vessels at 3 h, neuron-like cells at 6 and 12 h and glia-like cells at 12 h. Activation of JNK was not remarkable, and a few cells showed active JNK following ischemia. Phosphorylation of Elk-1, a transcription factor, was reduced by ischemic insult. Hypothermia attenuated the activation of ERK, p38 and JNK, and inhibited reduction of Elk-1. These data suggest that signals via different MAPK family members converge on the cell damage process and hypothermia protects the brain by interfering with these pathways.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.6
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• pp.1546-1551
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• 2005

This Study was designed to investigate the effects of Nelumbinis Rhizomatis Nodus (NRN) 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, this study was designed to investigate the inhibition of lactate dehydrogenase activity in neuronal cells The results were as follows NRN significantly increased rCBF and PAD in a dose-dependent manner, and NRN increased MABP in a dose-dependent manner. This results suggested that NRN significantly increased rCBF by dilating PAD. Both rCBF and PAD were significantly and stably increased by NRN (10 mg/kg, i.p.) during the period of cerebral reperfusion, which contrasted with the findings of rapid and marked increase in control group. NRN significantly inhibited lactate dehydrogenase activity in neuronal cells. This results suggested that NRN prevented the neuronal death. It is suggested that NRN had an anti-ischemic effect through the improvement of cerebral hemodynamics and inhibitive effect on the brain damage.

• Journal of International Academy of Physical Therapy Research
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• v.7 no.2
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• pp.1031-1036
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• 2016

c-Fos is known to related to synaptic plasticity and apoptosis in damage from ischemia or external injury. The purpose of this study was to investigate whether needle electrode electrical stimulation(NEES) is effective in increasing the number of c-Fos response cells and c-Fos expression in striatum after global ischemia in rats. There were no treatment and occlusion in the control group, global ischemia(GI) group were no treatment after carotid artery occlusion, and needle electrode electrical stimulation(NEES) group were treated with NEES after GI induced. The number of striatum c-Fos response cells and c-Fos protein expression significantly decreased in the NEES group compared to the GI group after 12, 24, 48 hours. The results of the present study suggest that NEES is ineffective in improving global ischemia in rats and may also be ineffective in the globally ischemic human brain.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.1
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• pp.25-30
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• 2006

This Study was designed to investigate the effects of Patholobi Caulis on the change of regional cerebral blood flow (rCBF) and blood Pressure (MABP) in normal and Cerebral ischemic rats. And, this Study was designed to investigate the inhibition of lactate dehydrogenase (LDH) activity in neuronal cells. The results were as follows : In normal rats, Patholobi Caulis significantly increased rCBF in a dose-dependent manner, and MABP was somewhat increased. In ischemia rats, rCBF was significantly and stably increased by Patholobi Caulis (10 mg/kg, i.p.) during the period of cerebral reperfusion, which contrasted with the findings of rapid and marked increase in control group. Patholobi Caulis significantly inhibited LDH activity in neuronal cells. It was suggested that Patholobi Caulis had an anti-ischemic effect through the improvement of cerebral hemodynamics and inhibitive effect on the brain damage.

• Journal of International Academy of Physical Therapy Research
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• v.1 no.2
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• pp.107-112
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• 2010

The majority of strokes are caused by ischemia and result in brain tissue damage, leading to problems of the central nervous system including hemiparesis, dysfunction of language and consciousness, and dysfunction of perception. The purpose of this study was to investigate the effects of Poly(ADP-ribose) polymerase(PARP) on necrosis in neuronal cells that have undergone needle electrode electrical stimulation(NEES) prior to induction of ischemia. Ischemia was induced in male SD rats(body weight 300g) by occlusion of the common carotid artery for 5 min, after which the blood was reperfused. After induction of brain ischemia, NEES was applied to Zusanli(ST 36), at 12, 24 and 48 hours. Protein expression was investigated using immuno-reactive cells, which react to PARP antibodies in cerebral nerve cells, and Western blotting. The results were as follows: In the cerebral cortex, the number of PARP reactive cells after 24 hours significantly decreased(p<.05) in the NEES group compared to the GI group. PARP expression after 24 hours significantly decreased(p<.05) in the NEES group compared to the GI group. As a result, NEES showed the greatest effect on necrosis-related PARP immuno-reactive cells 24 hours after ischemia, indicating necrosis inhibition, blocking of neural cell death, and protection of neural cells. Based on the results of this study, NEES can be an effective method of treating dysfunction and improving function of neuronal cells in brain damage caused by ischemia.

• The Korea Journal of Herbology
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• v.35 no.1
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• pp.1-8
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• 2020

Objectives : This study was conducted to evaluate the effects of Corni Fructus, the dried fruits of Cornus officinalis Sieb., on unilateral common carotid artery occlusion (UCCAO) in mouse model. Methods : The Corni Fructus used in the experiment was extracted with anhydrous methanol, then filtered and freeze-dried. C57BL/6 mice used in the experiments were conducted left UCCAO surgery to set up UCCAO rodent model for mice. The mice were divided into five groups for evaluate the effect of methanol extract of Corni Fructus (COM) on UCCAO induced ischemic brain injury. The expression levels of nitric oxide in cerebrum and serum, body weight change were measured. To determine the effect of UCCAO and COM administration on brain neurons, morphological changes of the cerebrum through a microscope was conducted. And western blot was performed to confirm the underlying mechanism of neuroprotective effect of COM administration. Results : COM administered UCCAO groups (CO50, CO150, and CO500) had no significant effects on nitric oxide production in ipsilateral hemisphere proteins and sera. The CO500, 500 mg/kg COM administration, attenuated UCCAO-induced p38 inflammatory signaling pathway and inflammatory mediators such as iNOS and COX-2. The CO500 group showed resilient morphological changes of hippocampus neuronal cells about brain damage caused by decreased flow of blood. These group also showed decreased inflammation and cellular stress response in neuronal cells. Conclusions : From these results, COM has a neuroprotective property via moderating inflammatory factors and cellular stress inducing factors in brain cells.