• Laboraroty Animal Research
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• v.33 no.3
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• pp.244-250
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• 2017

${\alpha}$-Synuclein is abundantly expressed in neuronal tissue, plays an essential role in the pathogenesis of neurodegenerative disorders, and exerts a neuroprotective effect against oxidative stress. Cerebral ischemia causes severe neurological disorders and neuronal dysfunction. In this study, we examined ${\alpha}$-synuclein expression in middle cerebral artery occlusion (MCAO)-induced cerebral ischemic injury and neuronal cells damaged by glutamate treatment. MCAO surgical operation was performed on male Sprague-Dawley rats, and brain samples were isolated 24 hours after MCAO. We confirmed neurological behavior deficit, infarction area, and histopathological changes following MCAO injury. A proteomic approach and Western blot analysis demonstrated a decrease in ${\alpha}$-synuclein in the cerebral cortices after MCAO injury. Moreover, glutamate treatment induced neuronal cell death and decreased ${\alpha}$-synuclein expression in a hippocampal-derived cell line in a dose-dependent manner. It is known that ${\alpha}$-synuclein regulates neuronal survival, and low levels of ${\alpha}$-synuclein expression result in cytotoxicity. Thus, these results suggest that cerebral ischemic injury leads to a reduction in ${\alpha}$-synuclein and consequently causes serious brain damage.

• Food Science and Biotechnology
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• v.15 no.2
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• pp.244-247
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• 2006

Neuronal cell death significantly contributes to neuronal loss in neurological injury and disease. Typically, neuronal loss or destruction upon exposure to neurotoxins, oxidative stress, or DNA damage causes neurodegenerative diseases such as Alzheimer's disease. In this study, we attempted to determine whether ginsenoside Rg3 from red ginseng has a neuroprotective effect via an anti-apoptotic role induced by S-nitroso-N-acetylpenicillamine (SNAP) at the molecular level. We also investigated the antioxidant effect of Rg3 using a metal-catalyzed reaction with $Cu^{2+}/H_2O_2$. Our results showed that Rg3 ($40-100\;{\mu}g/mL$) protected SK-N-MC neuroblastoma cells under cytotoxic conditions and effectively protected DNA from fragmentation. In the signal pathway, caspase-3, and poly (ADP-ribose) polymerase (PARP) were kept at an inactivated status when pretreated with Rg3 in all ranges. In particular, the important upstream p-Akt signal pathway was increased in a dose-dependent manner, which indicates that Rg3 may contribute to cell survival. We also found that oxidative stress can be mitigated by Rg3. Therefore, we have concluded that Rg3 plays a certain role in neurodegenerative pathogenesis via an anti apoptotic, antioxidative effect.

• Journal of Korean Neurosurgical Society
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• v.38 no.2
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• pp.121-125
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• 2005

Objective : Many recent reports have shown that the mature mammalian brain harbors multipotent stem cells, rendering the brain capable of generating new neurons and glia throughout life. Harvested stem cells from an adult rat are transplanted in order to evaluate the cell survival and differentiation. Methods : Using a percoll gradient with a high speed centrifugation method, we isolate neural stem/progenitor cells were isolated from the subventricular zone[SVZ] of a syngeneic adult Fisher 344 rats brain. For 14days expansion, the cultured cells comprised of a heterogeneous population with the majority of cells expressing nestin and/or GFAP. After expanding the SVZ cells in the presence of basic fibroblast growth factor-2, and transplanting then into the hippocampus of normal rats, the survival and differentiation of those cells were examined. For transplantation, the cultured cells were labeled with BrdU two days prior to use. In order to test their survival, the cells were transplanted into the dorsal hippocampus of normal adult Fisher 344 rats. Results : The preliminary data showed that at 7days after transplantation, BrdU+ transplanted cells were observed around the injection deposition sites. Immuno-fluorescent microscopy revealed that the cells co-expressed BrdU+ and neuronal marker ${\beta}$-tubulin III. Conclusion : The data demonstrate that the in vitro expanded SVZ cells can survive in a heterotypic environment and develop a neuronal phenotype in the neurogenic region. However more research will be needed to examine the longer survival time points and quantifying the differentiation in the transplanted cells in an injured brain environment.

• Biomolecules & Therapeutics
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• v.27 no.2
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• pp.145-151
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• 2019

Methamphetamine (METH) acts strongly on the nervous system and damages neurons and is known to cause neurodegenerative diseases such as Alzheimer's and Parkinson's. Flavonoids, polyphenolic compounds present in green tea, red wine and several fruits exhibit antioxidant properties that protect neurons from oxidative damage and promote neuronal survival. Especially, epicatechin (EC) is a powerful flavonoid with antibacterial, antiviral, antitumor and antimutagenic effects as well as antioxidant effects. We therefore investigated whether EC could prevent METH-induced neurotoxicity using HT22 hippocampal neuronal cells. EC reduced METH-induced cell death of HT22 cells. In addition, we observed that EC abrogated the activation of ERK, p38 and inhibited the expression of CHOP and DR4. EC also reduced METH-induced ROS accumulation and MMP. These results suggest that EC may protect HT22 hippocampal neurons against METH-induced cell death by reducing ER stress and mitochondrial damage.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.134.1-134.1
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• 2003

In regard to $A\beta$ toxicity and AD, reactive oxygen species (ROS) are produced by macrophage families in response to $A\beta$ stimulation. In addition to this, neurotrophins (NTs) regulate the neuronal function as well as cell survival and the growth of various types of neurons in both the peripheral nervous system (PNS) and central nervous system (CNS). As high expressions of the ROS and NTs are a routine findings in neuronal cell damage, we wanted to investigate whether Rg3 can inhibit the production of ROS and NTs primary cell cultures. (omitted)

• BMB Reports
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• v.35 no.1
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• pp.87-93
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• 2002

Neural cell survival is an essential concern in the aging brain and many diseases of the central nervous system. Neural transplantation of the stem cells are already applied to clinical trials for many degenerative neurological diseases, including Huntington's disease, Parkinson's disease, and strokes. A critical problem of the neural transplantation is how to reduce their apoptosis and improve cell survival. Neurotrophic factors generally contribute as extrinsic cues to promote cell survival of specific neurons in the developing mammalian brains, but the survival factor for neural stem cell is poorly defined. To understand the mechanism controlling stem cell death and improve cell survival of the transplanted stem cells, we investigated the effect of plausible neurotrophic factors on stem cell survival. The neural stem cell, HiB5, when treated with PDGF prior to transplantation, survived better than cells without PDGF. The resulting survival rate was two fold for four weeks and up to three fold for twelve weeks. When transplanted into dorsal hippocampus, they migrated along hippocampal alveus and integrated into pyramidal cell layers and dentate granule cell layers in an inside out sequence, which is perhaps the endogenous pathway that is similar to that in embryonic neurogenesis. Promotion of the long term-survival and differentiation of the transplanted neural precursors by PDGF may facilitate regeneration in the aging adult brain and probably in the injury sites of the brain.

• Journal of Life Science
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• v.18 no.3
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• pp.311-317
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• 2008

Pathophysiological oxidative stress results in neuronal cell death mainly due to the generation reactive oxygen species (ROS). In low oxygen situation such as hypoxia and ischemia, excessive ROS is generated. Coptidis Rhizoma (CR) is a traditional medicine used for the incipient stroke. In this report we show that CR water extracts $(1\;{\mu}g/ml)$ exhibited protective effects of neuronal cell death in a hypoxic model (2% $O_2/5%\;CO_2,\;37^{\circ}C,$ 3 hr) of cultured rat cortical cells. We further show that CR water extracts significantly reduced the intensity of green fluorescence after staining with $H_2DCF-DA$ on one hour and three days after hypoxic shock and in normoxia as well. Our results indicate that CR water extracts prevent neuronal death by suppressing ROS generation.

• Proceedings of the Zoological Society Korea Conference
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• 1999.10b
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• pp.181.1-181
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• 1999

No Abstract, See Full Text

• Journal of Medicine and Life Science
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• v.15 no.2
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• pp.67-71
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• 2018

Neuronal excitotoxicity induces mitochondrial dysfunction and the release of proapoptotic proteins. Excitotoxicity, the process by which the overactivation of excitatory neurotransmitter receptors leads to neuronal cell death. Neuronal death by excitotoxicity was related to neuronal degenerative disorders and hypoxia, results from excessive exposure to excitatory neurotransmitters, such as glutamate. Glutamate acts at NMDA receptors in cultured neurons to increase the intracellular free calcium concentration. Therefore endogenous glutamate may be a key factor to regulate neuronal cell death via activating $Ca^{2+}$ signaling. For this issue, we tested some conditions to alter intracellular $Ca^{2+}$ level in dissociated hippocampal neurons of rats. Cultured hippocampal neuron were treated by KCl (20 mM), $CaCl_2$ (3.8 mM) and glutamate ($5{\mu}M$) for 24 hrs. Interestingly, The Optical Density of hippocampal neurons was increased by high KCl application in MTT assay data. This enhanced response by high KCl was dependent on synaptic $Ca^{2+}$ influx but not on intracellular $Ca^{2+}$ level. However, the number of neurons seemed to be not changed in Hoechst 33342 staining data. These results suggest that enhancement of synaptic activity plays a key role to increase mitochondrial signaling in hippocampal neurons.

• Archives of Pharmacal Research
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• v.14 no.4
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• pp.325-329
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• 1991

Effects of Lycii Fructus on primary cultured chicken embryonic brain cells were studied by microscopic observation, determination of the activity of pyruvate dehydrogenase complex (PDHC), and syntheses of protein, RNA and DNA. The brain cells were prepared from the brains or 10-day-old chicken embryos and cultured with a deficient medium. The activity of PDHC in the brain cells cultured with a deficient medium was increased to 1.8 times by the addition of $30\;{\mu}g/ml$ of the total methanol extract of Lycii Fructus. To seek the active fraction, total methanol extract was further fractionated by the polarity. The survival rate of neuronal cells was significantly increased by the addition of $100\;{\mu}g/ml$ of the buthanol or aqueous fraction. At this concentration, the significant increase of the syntheses of protein and RNA, but not of DNA, indicates that the fractions may act on the neuronal cells which are known to be non-dividing cells.