• 약학회지
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• 제49권1호
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• pp.30-37
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• 2005

Xuesaitong Ruanjiaonang (XR), a soft capsule containing Panax notoginseng saponins as main ingredients, is believed to remove extravasated blood and increase cerebral blood flow by improving blood circulation, and therefore, has been used in China to treat ischemic stroke or hemiplegia caused by cerebral thrombosis. To characterize pharmacological actions of XR, the present study evaluated its effects on neuronal cell damage induced by various oxidative insults or excitotoxic amino acids in primary cultured rat cortical cells. The neuronal cell viability was not affected by XR with the exposure for 2 h at the concentrations tested in this study ($10{\sim}1000\;{\mu}g/ml$). However, significant reduction of the cell viability was observed when the cultured cells were exposed to XR at $1000\;{\mu}g/ml$ for 24 h. XR was found to concentration-dependently inhibit the oxidative neuronal damage induced by $H_{2}O_2$, xanthine/xanthine oxidase or $Fe^{2+}$/ascorbic acid. In addition, it dramatically inhibited the excitotoxic damage induced by glutamate or N-methyl-D-aspartate (NMDA). We found that the NMDA-induced neurotoxicity was inhibited more effectively and potently than the glutamate-induced toxicity. Moreover, XR was found to exert mild inhibition of lipid peroxidation induced by $Fe^{2+}$/ascorbic acid in rat brain homogenates and some 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity. Taken together, these results demonstrate neuroprotective and antioxidant effects of XR, showing inhibition of oxidative and excitotoxic damage in the cultured cortical neurons, as well as inhibition of lipid peroxidation and its radical scavenging activity. Considering that excitotoxicity and oxidative stress pl ay crucial roles in neuronal cell damage during ischemia and reperfusion, these results may provide pharmacological basis for its clinical usage to treat ischemic stroke.

• Archives of Pharmacal Research
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• 제11권4호
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• pp.301-307
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• 1988

Relationship between the maintenance of hypertension and central serotonergic nervous system activity in opontaneously hypertensive rats (SHR) was studied. Serotonin turnover-rates were measured in 5 brain areas as an index of serotonergic neuronal activity and compared at the ages of 14 weeks in two types of animals; (1) spontaneously hypertensive rats (SHR) (2) normotensive wistar kyoto rats (WKY). In 14-week old SHR, central serotonin turnover rate was significantly lower in telencephalon, hypothalamus/thalamus and midbrain than normotensive rat, but significantly higher in cerebellum. There were no significant differences between serotonin turnover rate in pons/medulla of SHR and that of normotensive rat. THese data suggest that the abnormally lower turnover rates of serotonin in telencephalon, hypothalamus/thalamus and midbrain may be one of the underlying neuronal factors for manifestation of hypertension in SHR.

• Molecular & Cellular Toxicology
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• 제4권1호
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• pp.16-21
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• 2008

Cell death of trophoblast, particularly by abnormal release of physiological nitric oxide (NO) has been known to be a causative factor of pre-eclampsia. In the present study, effects of intracellular calcium increase enhancing the activity of NO synthases (neuronal NO synthase, nNOS in this trophoblast cells) on the cell death were examined in a human placental full-term cell line (HT-1). Furthermore, we analyzed the possible mechanisms underlying the augmentation of $Ca^{++}$-mediated NOS activity mediated by protein kinases like PKC, PKA, or CaM-KII. In experiments for cell toxicity, a calcium ionophore (ionomycin $10{\mu}M$) enhanced cell death confirmed by MTT assay, and increased significantly nNOS activity determined with a hemoglobin oxidation assay. This cell death was partially protected by pre-treatment of 7-nitroindazole (7-NI, $10{\mu}M$ and $100{\mu}M$), a nNOS-specific inhibitor. Additionally, $Ca^{++}$-ionophore -induced increase of nNOS activity also was partially normalized by pre-treatment of specific inhibitors of protein kinases, PKC, PKA or CaM-KII. Therefore, we suggest that an increase of calcium influx, leading to the activation of nNOS activity, which in turn may result in the death of trophoblast cells by involvement of signaling mechanisms of protein kinases.

• 제어로봇시스템학회논문지
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• 제13권9호
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• pp.838-842
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• 2007

A brain-computer interface(BCI) system is a communication channel which transforms a subject's thought process into command signals to control various devices. These systems use electroencephalographic signals or the neuronal activity of many single neurons. The presented study deals with an efficient analysis method of neuronal signals from a BCI System using an independent component analysis(ICA) algorithm. The BCI system was implemented to generate event signals coding movement information of the subject. To apply the ICA algorithm, we obtained the perievent histograms of neuronal signals recorded from prefrontal cortex(PFC) region during target-to-goal(TG) task trials in the BCI system. The neuronal signals were then smoothed over 5ms intervals by low-pass filtering. The matrix of smoothed signals was then rearranged such that each signal was represented as a column and each bin as a row. Each column was also normalized to have a unit variance. As a result, we verified that different patterns of the neuronal signals are dependent on the target position and predefined event signals.

• Archives of Pharmacal Research
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• 제22권1호
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• pp.35-43
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• 1999

Overstimulation of both kainate (KA) and N-methyl-D-aspartate (NMDA) receptors has been reported to induce excitatoxicity which can be characterized by neuronal damage and formation of reactive oxygen free radicals. Neuroprotective effect of melatonin against KA-induced excitotoxicity have been documented in vitro and in vivo. It is, however, not clear whether melationin is also neuroportective against excitotoxicity mediated by NMDA receptors. In the present work, we tested the in vivo protective effects of striatally infused melatonin against the oxidative stress and neuronal damage induced by the injection of KA and NMDA receptors into the rat striatum. Melatonin implants consisting of 22-gauge stainless-steel cannule with melatonin fused inside the tip were placed bilaterally in the rat brain one week prior to intrastriatal injection of glutamate receptor subtype agonists. Melatonin showed protective effects against the elevation of lipid peroxidation induced by either KA or NMDA and recovered Cu, Zn-superoxide dismutase activities reduced by both KA and NMDA into the control level. Melatonin also clearly blocked both KA- and NMDA-receptor mediated neuronal damage assessed by the determination of choline acetyltransferase activity in striatal monogenages and by microscopic observation of rat brain section stained with cresyl violet. The protective effects of melatonin are comparable to those of DNQX and MK801 which are the KA- and NMDA-receptor antagonist, respectively. It is suggested that melatonin could protect against striatal oxidative damages mediated by glutamate receptors, both non-NMDA and NMDA receptors.

• 대한임상검사과학회지
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• 제52권4호
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• pp.389-397
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• 2020

Microglial cells function as major immune cells in the brain, playing an important role in the protection and damage of neurons. BV2 microglia, activated by drug stimulation, secrete inflammatory cytokines by activating the nuclear factor kappa-light-chain-enhancer of the activated B cells pathway and are involved in neuroinflammatory and immune responses. The overactivation of microglia by stimuli can cause neuronal damage, leading to brain disease. Noni, a natural product, reduces the activity of microglia to prevent neuronal damage and is a potential natural medicine because it exerts excellent regeneration and anti-inflammatory effects on damaged cells. In this study, when noni was used to treat BV2 cells stimulated by the anti-cancer drug doxorubicin, it reduced the release of pro-inflammatory cytokines from BV2. On the other hand, neuronal damage is a side effect of doxorubicin. Therefore, the cytokines released from doxorubicin-stimulated BV2 cells treated with noni had a positive effect on the neuronal viability compared to those released from doxorubicin-stimulated BV2 cells not treated with Noni. Thus, Noni increases neuronal viability. These results suggest that noni inhibits the release of cytokines by regulating the nuclear factor kappa-light-chain-enhancer of the activated B cells pathway of BV2, thereby inhibiting neuronal damage.

• The Korean Journal of Physiology and Pharmacology
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• 제9권1호
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• pp.9-15
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• 2005

We attempted to analyze the mechanism of polychlorinated biphenyl (PCB)-induced neurotoxicity and identify the target molecules in the neuronal cells for PCBs.Since the developing neuron is particularly sensitive to PCB-induced neurotoxicity, we isolated cerebellar granule cells derived from 7-day old Sprague Dawley (SD) rats and grew cells in culture for additional 7 days to mimic PND-14 conditions. Only non-coplanar PCBs at a high dose showed a significant increase of total protein kinase C (PKC) activity at phobol 12,13-dibutyrate ([$^3M$]PDBu) binding assay, indicating that non-coplanar PCBs are more neuroactive than coplanar PCBs in neuronal cells. PKC isozymes were immunoblotted with the selected monoclonal antibodies. PKC-${\alpha}$, ${\delta}$, and ε were activated with non-coplanar PCB exposure. Receptor for activated C kinase-1 (RACK-1), anchoring protein for activated PKC, was more induced with exposure to coplanar PCBs than non-coplanar PCBs. Reverse transcription PCR (RT-PCR) analysis showed induction of neurogranin (RC-3) and growth associated protein-43 (GAP-43) mRNA with non-coplanar PCBs. The results indicate that these factors may be useful biomarkers for differentiating non-coplanar PCBs from coplanar PCBs. The present study demonstrated that non-coplanar PCBs are more neuroactive congeners than coplanar PCBs.

• 동의생리병리학회지
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• 제19권6호
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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.

• 대한의용생체공학회:의공학회지
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• 제17권1호
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• pp.79-84
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• 1996

A number of experimental evidences suggest that the rnun ventrolateral medulla(RVLM) is the final common pathway in the regulation of arterial blood pressure. A Voup of neurons in the RVLM, called the cardiovascular neurons (UN), show spontaneous activity temporally synchronized with the periodic cardiac cycle. These neurons affect the sympathetic nerve discharge(SND), thus are believed to be responsible for blood pressure control. The present experiment identified 98 UVNs in 42 cats based on the temporal relationships between each neuron's activity with both the cardiac cycle and SWD. In 20 UWL changes of spontaneous firing rate(FR) during the somatosympathetic reflex(SSR) were studied Five different firing patterns were observed during the pressor and depressor responses of SSR, implying that they form an interconnected neuronal circuit interacting with one another to generate efferent signals for blood pressure regulation. In the following companion paper, the firing patterns of CVN are analyzed to develop a minimal neuronal circuit model explaining the present experimental outcome.

• Journal of Korean Biological Nursing Science
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• 제24권2호
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• pp.77-85
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• 2022

Purpose: Aging process comes with cognitive impairment due to decreased neuronal cell number, activity, and neuronal circuit. Alteration of inhibitory neurons contributes to cognitive impairment in normal aging and is responsible for disrupting the excitation/inhibition balance by reducing the synthesis of gamma-aminobutyric acid (GABA). Morus nigra (Mulberry) is a natural physiologically active substance that has been proven to have anti-oxidant, anti-diabetic, and anti-inflammatory effects through many studies. This study aimed to evaluate the effects of the mulberry extract (ME) on cognitive function through anti-oxidant enzyme and GABAergic neuronal activity in aged rat brain. Methods: Sprague Dawley rats were randomly assigned as the young group (8 weeks, n= 8), aging group (67 weeks, n= 8), and aging+ mulberry extract group (67 weeks, n= 8). The aging+ mulberry extract group was orally administered 500 mg/kg/d mulberry extract for 6 weeks. Results: The aging+ mulberry extract group improved spatial and short-term memory. The antioxidant potential of ME increased the expression of superoxide dismutase-1 (SOD-1) and decreased inducible nitric oxide synthase (iNOS). Also, the aging+ mulberry extract group significantly increased the expression of GABAergic interneuron in hippocampus cornu ammonis1 (CA1) compared to the aging group. Conclusion: The number of GABAergic inhibitory interneurons was deceased and memory functions in the aging process, but those symptoms were improved and restored by mulberry extract administration.