• Journal of Physiology & Pathology in Korean Medicine
• /
• v.27 no.2
• /
• pp.173-182
• /
• 2013

This Study was designed to investigate the effects of Sibjeondaebo-tang (SDT) and Gamy-Sibjeondaebo-tang (GST, Sibjeondaebo-tang adding Cervi Pantotrichum Cornu) on the improvement in regional cerebral blood flow (rCBF) and mean arterial blood pressure (MABP) in normal rats, and in the rats with cerebral ischemia induced by middle cerebral artery occlusion, and further to determine the mechanisms. And, It was to investigate the effects of the SDT and GST with the change of histologic examination through the BDNF in the hippocampus CA1. In changes of cerebral hemodynamics, SDT and GST significantly increased rCBF in a dose-dependent manner but decreased MABP in normal rats. In mechanism of cerebral hemodynamics, Increase of GST-induced rCBF was significantly inhibited by pretreatment with methylene blue (0.01 mg/kg, i.p.), an inhibitor of guanylate cyclase, and Decrease of GST-induced MABP was significantly increased by pretreatment with methylene. These results suggested that the action of GST was mediated by guantlate cyclase pathway. In cerebral ischemics, the rCBF was stably improved by SDT (10 mg/kg, i.p.) significantly and stably increased by GST (10 mg/kg, i.p.) during the period of cerebral reperfusion, which contrast with the findings of rapid and marked increase in Control group. These results suggested that GST had anti-ischemic action in cerebral ischemic state. In histological examination through TTC stain, Sample A group and Sample B group decreased discoloration in the cortical part at $28^{th}$ day after MCAO induction. In immunohistochemistric response of BDNF, Sample A group and Sample B group increased respondent effect at $28^{th}$ day after MCAO induction. These results suggest that GST can Increase rCBF in normal state, as well as improve the stability of rCBF in cerebral ischemic state. Furthermore, methylene blue inhibitor study suggested the mechanism of blood flow enhancement by GST may be mediated by guanylate cyclase pathway.

• The Korean Journal of Physiology and Pharmacology
• /
• v.8 no.3
• /
• pp.141-146
• /
• 2004

Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) proteins, composed of two presynaptic membrane proteins [synaptosomal-associated protein of 25 kDa (SNAP-25) and syntaxin] and a presynaptic vesicular protein [vesicle-associated membrane protein (VAMP)], serve as a core of exocytotic fusion machinery, which can be affected by ischemia. Synaptic protein in core region, striatum and cortex has been shown to alter after focal ischemia, however, little is known in hippocampus. Hippocampus is remote from ischemic core, but it is one of the most vulnerable regions. Using immunohistochemistry, the present study was undertaken to investigate the alteration of expression of SNAP-25, syntaxin, and VAMP in the hippocampus of rats which were subjected to middle cerebral artery occlusion (MCAO) for 2h and allowed to reperfuse. At 2 weeks of reperfusion, the SNAP-25 and syntaxin immunoreactivity was increased in the stratum oriens of the CA1 and the stratum lucidum of the CA3 in the ipsilateral hippocampus. However, VAMP immunoreactivity didn't show significant change. These results demonstrate that the level of the presynatpic plasma membrane proteins (SNAP-25 and syntaxin) in the rat hippocampus is more sensitively affected by focal ischemia than that of the synaptic vesicle protein (VAMP).

• The Korean Journal of Physiology and Pharmacology
• /
• v.14 no.3
• /
• pp.127-132
• /
• 2010

Reactive oxygen species (ROS), which include hydrogen peroxide ($H_2O_2$), the superoxide anion (${O_2}^-{\cdot}$), and the hydroxyl radical ($OH{\cdot}$), are generated as by-products of oxidative metabolism in cells. The cerebral cortex has been found to be particularly vulnerable to production of ROS associated with conditions such as ischemia-reperfusion, Parkinson's disease, and aging. To investigate the effect of ROS on inhibitory GABAergic synaptic transmission, we examined the electrophysiological mechanisms of the modulatory effect of $H_2O_2$ on GABAergic miniature inhibitory postsynaptic current (mIPSCs) in mechanically isolated rat cerebral cortical neurons retaining intact synaptic boutons. The membrane potential was voltage-clamped at -60 mV and mIPSCs were recorded and analyzed. Superfusion of 1-mM $H_2O_2$ gradually potentiated mIPSCs. This potentiating effect of $H_2O_2$ was blocked by the pretreatment with either 10,000-unit/mL catalase or $300-{\mu}M$ N-acetyl-cysteine. The potentiating effect of $H_2O_2$ was occluded by an adenylate cyclase activator, forskolin, and was blocked by a protein kinase A inhibitor, N -(2-[p-bromocinnamylamino] ethyl)-5-isoquinolinesulfonamide hydrochloride. This study indicates that oxidative stress may potentiate presynaptic GABA release through the mechanism of cAMP-dependent protein kinase A (PKA)-dependent pathways, which may result in the inhibition of the cerebral cortex neuronal activity.

• The Korean Journal of Physiology and Pharmacology
• /
• v.20 no.2
• /
• pp.185-192
• /
• 2016

Ampicillin, a ${\beta}$-lactam antibiotic, dose-dependently protects neurons against ischemic brain injury. The present study was performed to investigate the neuroprotective mechanism of ampicillin in a mouse model of transient global forebrain ischemia. Male C57BL/6 mice were anesthetized with halothane and subjected to bilateral common carotid artery occlusion for 40 min. Before transient forebrain ischemia, ampicillin (200 mg/kg, intraperitoneally [i.p.]) or penicillin G (6,000 U/kg or 20,000 U/kg, i.p.) was administered daily for 5 days. The pretreatment with ampicillin but not with penicillin G significantly attenuated neuronal damage in the hippocampal CA1 subfield. Mechanistically, the increased activity of matrix metalloproteinases (MMPs) following forebrain ischemia was also attenuated by ampicillin treatment. In addition, the ampicillin treatment reversed increased immunoreactivities to glial fibrillary acidic protein and isolectin B4, markers of astrocytes and microglia, respectively. Furthermore, the ampicillin treatment significantly increased the level of glutamate transporter-1, and dihydrokainic acid (DHK, 10 mg/kg, i.p.), an inhibitor of glutamate transporter-1 (GLT-1), reversed the neuroprotective effect of ampicillin. Taken together, these data indicate that ampicillin provides neuroprotection against ischemia-reperfusion brain injury, possibly through inducing the GLT-1 protein and inhibiting the activity of MMP in the mouse hippocampus.

• Journal of Korean Neurosurgical Society
• /
• v.40 no.2
• /
• pp.103-109
• /
• 2006

Objective : Activated endothelial cells mediate the cascade of reactions in response to hypoxia for adaptation to the stress. It has been suggested that hypoxia, by itself, without reperfusion, can activate the endothelial cells and initiate complex responses. In this study, we investigated whether hypoxia-induced endothelial products alter the endothelial permeability and have a direct cytotoxic effect on nerve cells. Methods : Hypoxic condition of primary human umbilical vein endothelial cells[HUVEC] was induced by $CoCl_2$ treatment in culture medium. Cell growth was evaluated by 3,4,5-dimethyl thiazole-3,5-diphenyl tetrazolium bromide [MTT] assay Hypoxia-induced products [$IL-1{\beta},\;TGF-{\beta}1,\;IFN-{\gamma},\;TNF-{\alpha}$, IL-10, IL-6, IL-8, MCP-l and VEGF] were assessed by enzyme-linked immunosorbent assay. Endothelial permeability was evaluated by Western blotting. Results : Prolonged hypoxia caused endothelial cells to secrete IL -6, IL -8, MCP-1 and VEGF. However, the levels of IL -1, IL -10, $TNF-{\alpha},\;TGF-{\beta},\;IFN-{\gamma}$ and nitric oxide remained unchanged over 48 h hypoxia. Hypoxic exposure to endothelial cells induced the time-dependent down regulation of the expression of cadherin and catenin protein. The conditioned medium taken from hypoxic HUVECs had the cytotoxic effect selectively on neuroblastoma cells, but not on astroglioma cells. Conclusion : These results suggest the possibility that endothelial cell derived cytokines or other secreted products with the increased endothelial permeability might directly contribute to nerve cell injury followed by hypoxia.

• Journal of International Academy of Physical Therapy Research
• /
• v.6 no.2
• /
• pp.846-851
• /
• 2015

This neurological damage accelerates the infection reaction of cells and apoptosis at the time of reperfusion after ischemia occurs. BCL-2/BCL-2 allogeneic begeminum has a function of suppressing the apoptosis of cells, and thus it is inferred that the susceptibility of cells to apoptosis is determined by the amount of allogeneic begeminum present which is determined based on the amount of BAX. Ischemia was induced in SD mice by occluding the common carotid artery for 5 minutes, after which blood was re-perfused. NEES was applied to acupuncture points, at 12, 24, and 48 hours post-ischemia on the joksamri, Hapgok. Protein expression was investigated through BAX antibody immuno-reactive cells in the cerebral nerve cells and Western blotting. The results were as follows: In the present study as well, as a result of observation of the change in the number of the BAX reaction cells after the inducement of GI, there was the aspect of most of the BAX reaction cells being observed in the corpus striatum area of the GI group 24 hours after the inducement of ischemia. This revealed the same results as those of previous studies in which the change in the number of BAX reaction cells occurred in all areas while ischemia was in progress. The change in the expression of BAX protein after 24 hours showed that there was a very significant reduction in the NEES group compared to the GI group (p<.01). As a result, a greatest amount of change in the number of BAX immunoreactive cells related to apoptosis 24 hours after ischemia appeared in the NEES group. This study that ischemia increases the expression of BAX that induces apoptosis. Thus, it is determined that ischemia is the main cause of the apoptosis of neurons, and this study reveals that low frequency needle electrode electrical stimulation has the effect of blocking the apoptosis of neurons by reducing protein related to the apoptosis of cells that has increased after ischemia has occurred.

• Journal of Chest Surgery
• /
• v.29 no.3
• /
• pp.303-310
• /
• 1996

From December of 1994 to April of 1995, we, SHUH Department of Pediatric Thoracic and Cardiovascular Surgery, studied effects of aprotinin. 95 patients were randomly divided into two groups : group I (n=47) with aprotinin and group ll (n=48) without aprotinin. Aprotinin was given as one shot injection to cardiopulmonary bypass perfusion solution with dose of 50,000 KIUikg. Laboratory data such as hemoglobin, hematocrit, BUH, creatinine, fibrinogen, electrolyte concentration, aPTT, PT, and AT R was checked preoperatively, 5 minutes after anesthesia, 5 minutes and 35 minutes after CPB circulation, and 5 minutes, 3 hours, and 24 hours after reperfusion. Also, chest-tube drainage, transfused amount of RBC, platelet concentrate, and fresh frozen plasma within first 24 hours postoperatively were checked and analyzed after transition nn body weight demension. Only RBC transfused postoperatively had statistical significance with P value of less than 0.001. Others had no difference statistical wise. Postoperative side effects of aprotinin was not detected weeks after the surgery and there was no reoperated patient due to postoperative bleeding.

• The Korea Journal of Herbology
• /
• v.27 no.2
• /
• pp.61-67
• /
• 2012

Objective : Angelica Gigas Nakai is a popular oriental medicine used for the treatment of vascular diseases. The aim of this study is to investigate neuroprotective effect of the water extract of Anelicae Gigantis Radix Palva (AG) in transient middle cerebral artery occlusion (tMCAO)-induced ischemic rats via the regulation of angiogenesis-related molecules. Methods : Sprague-Dawley rats were intraperitoneally administrated with AG water extract at doses of 10, 25, 50 mg/kg body weight after tMCAO (90 min occlusion). reperfusion for 24 hr infarction volumes were measured by 2,3,5-tetrazolium chloride (TTC) staining. Brain tissues were observed neuronal cell injuries by nissl staining, and also brain-blood barrier (BBB) permeability change by evans blue. Expression of vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1) and Tie-2 receptor protein in brain tissues was determined by western blot. Results : AG water extract significantly reduced infarction volume in ischemic brains of rats, degradation of neuronal cell, BBB permeability and expression of VEGF protein dose-dependently. Ang-1 protein was increased dose-dependantly, not significantly. Conclusion : This study suggests that AG water extract shows neuroprotective effect by preventing BBB breakdown, with regulating angiogenesis factor VEGF and Ang-1.

• 한국생물공학회:학술대회논문집
• /
• 2005.10a
• /
• pp.868-869
• /
• 2005

• Molecules and Cells
• /
• v.40 no.11
• /
• pp.837-846
• /
• 2017

As a component of the neurovascular unit, cerebral smooth muscle cells (CSMCs) are an important mediator in the development of cerebral vascular diseases such as stroke. Epoxyeicosatrienoic acids (EETs) are the products of arachidonic acid catalyzed by cytochrome P450 epoxygenase. EETs are shown to exert neuroprotective effects. In this article, the role of EET in the growth and apoptosis of CSMCs and the underlying mechanisms under oxygen glucose deprivation (OGD) conditions were addressed. The viability of CMSCs was decreased significantly in the OGD group, while different subtypes of EETs, especially 14,15-EET, could increase the viability of CSMCs under OGD conditions. RAPA (serine/threonine kinase Mammalian Target of Rapamycin), a specific mTOR inhibitor, could elevate the level of oxygen free radicals in CSMCs as well as the anti-apoptotic effects of 14,15-EET under OGD conditions. However, SP600125, a specific JNK (c-Jun N-terminal protein kinase) pathway inhibitor, could attenuate oxygen free radicals levels in CSMCs as well as the anti-apoptotic effects of 14,15-EET under OGD conditions. These results strongly suggest that EETs exert protective functions during the growth and apoptosis of CSMCs, via the JNK/c-Jun and mTOR signaling pathways in vitro. We are the first to disclose the beneficial roles and underlying mechanism of 14,15-EET in CSMC under OGD conditions.