• Science of Emotion and Sensibility
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• v.7 no.2
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• pp.179-186
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• 2004

Acute spinal cord injury can produce neurologic injury with many physical, psychological and social ramifications. It has been shown that two separate components combine to produce neurologic damage in acute spinal cord injury : the primary and secondary injuries. The primary mediators of spinal cord injury include the actual mechanical tissue disruption which is a passive process that occurs immediately following the trauma. A secondary injury cascade follows which appears mediated by cellular and molecular processes working through complex mechanisms. Both the primary and secondary injury cascades produce cell death both in neuronal and supporting cell tissues. Recovery from central nervous system(CNS) disorders is hindered by the limited ability of the vertebrate CNS to regenerate injured cells, replace damaged myelin sheath, and re-establish functional neuronal connections. Of many CNS disorders including multiple sclerosis, stroke, and other trauma, spinal cord injury is one of the important diseases because of the direct association with the functional loss of the body. Previous studies suggest that substantial recovery of function might be achieved through regeneration of lost neuronal cells and remyelination of intact axon in spinal cord injury which is occurred frequently. As a therapeutic approach in spinal cord injury, recently, cell transplantation provides a potential solution for the treatment of spinal cord injury. This review describes the characteristics of spinal cord injury and presents some evidence supporting functional recovery after cell transplantation following spinal cord injury.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.6
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• pp.309-315
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• 2006

The protective effects of baicalein, one of the flavonoids in Scutellaria baicalensis Georgi, were evaluated against 6-hydroxydopamine (6-OHDA)-induced neuronal damage in mice and cultured human neuroblastoma cells. Nigrostriatal damage was induced by stereotaxically injecting 6-OHDA into the right striatum. Baicalein was administered intraperitoneally 30 min before and 90 min after lesion induction. Animals received a further daily injection of baicalein for 3 consecutive days. Two weeks after 6-OHDA injection, contralateral rotational asymmetry was observed by apomorphine challenge in lesioned mice. Tyrosine hydroxylase (TH) immunohistochemistry revealed a significant loss of terminals in lesioned striatum and the reduction of the numbers of TH-positive cell in the ipsilateral substantia nigra (SN). In addition, the levels of dopamine (DA) and DA metabolites were reduced and lipid peroxidation was increased in lesioned striatum. However, baicalein treatment reduced apomorphine-induced rotational behavior in 6-OHDA-lesioned mice, and increased TH immunoreactivity in the striatum and SN, and DA levels in lesioned striatum. Lipid peroxidation induced by 6-OHDA was also inhibited by baicalein treatment. Furthermore, when SH-SY5Y human neuroblastoma cells were treated with baicalein, 6-OHDA-induced cytotoxicity and reactive oxygen species (ROS) production were significantly reduced. These results indicate that baicalein effectively protects 6-OHDA-induced neuronal damage through antioxidant action.

• The Korea Journal of Herbology
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• v.27 no.6
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• pp.83-90
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• 2012

Objectives : Modified Bo-Yang-Hwan-O-Tang (mBHT) is a polyherbal medicine of twelve herbs traditionally used in the treatment of cerebral and cardiac stroke and vascular dementia. The purpose of this study was to evaluate the neuroprotective effect, pyramidal neuronal cell, inflammation and apoptosis of mBHT against global ischemia in rats. Methods : Global ischemia was produced by two-vessel occlusion(2-VO) in SD male rats. mBHT at dose of 500 mg/kg was orally administrated for 2 weeks or 6 weeks after global ischemia. The histopathological changes of ischemic brain were observed by staining of hematoxylin and eosin (H&E) and Nissl and immunohistochemisty with anti-GFAP (glial fibrillary acidic protein) antibody as a astrocyte marker. The expression of inducible nitric oxide synthase (iNOS) and apoptotic proteins such as Bax, Bcl-2 and caspase-3 was determined by western blot. Results : mBHT treatment significantly inhibited the pyramidal neuronal loss in CA1 of hippocampus of global ischemic rats by 2-VO. mBHT also suppressed the activation of astrocytes in the CA1 at 6 weeks after ischemia. In addition, mBHT significantly increased the expression of anti-apoptotic protein, Bcl-2 on iscemic brain, and significantly attenuated the expression of apoptotic proteins, Bax and caspase-3. Conclusions : These results indicate that mBHT inhibits neuronal cell damage induced in global ischemia by 2-VO, suggesting that mBHT may be a potential candidate for the treatment of vascular dementia.

• Biomolecules & Therapeutics
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• v.31 no.3
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• pp.264-275
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• 2023

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by tremors, bradykinesia, and rigidity. PD is caused by loss of dopaminergic (DA) neurons in the midbrain substantia nigra (SN) and therefore, replenishment of DA neurons via stem cell-based therapy is a potential treatment option. Astrocytes are the most abundant non-neuronal cells in the central nervous system and are promising candidates for reprogramming into neuronal cells because they share a common origin with neurons. The ability of neural progenitor cells (NPCs) to proliferate and differentiate may overcome the limitations of the reduced viability and function of transplanted cells after cell replacement therapy. Achaete-scute complex homolog-like 1 (Ascl1) is a well-known neuronal-specific factor that induces various cell types such as human and mouse astrocytes and fibroblasts to differentiate into neurons. Nurr1 is involved in the differentiation and maintenance of DA neurons, and decreased Nurr1 expression is known to be a major risk factor for PD. Previous studies have shown that direct conversion of astrocytes into DA neurons and NPCs can be induced by overexpression of Ascl1 and Nurr1 and additional transcription factors genes such as superoxide dismutase 1 and SRY-box 2. Here, we demonstrate that astrocytes isolated from the ventral midbrain, the origin of SN DA neurons, can be effectively converted into DA neurons and NPCs with enhanced viability. In addition, when these NPCs are inducted to differentiate, they exhibit key characteristics of DA neurons. Thus, direct conversion of midbrain astrocytes is a possible cell therapy strategy to treat neurodegenerative diseases.

• Anatomy and Cell Biology
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• v.56 no.4
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• pp.494-507
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• 2023

Vascular dementia (VaD) is characterized by progressive memory impairment, which is associated with microglia-mediated neuroinflammation. Polyphenol-rich natural plants, which possess anti-inflammatory activities, have attracted scientific interest worldwide. This study investigated whether Rubus fruticosus leaf extract (RFLE) can attenuate VaD. Sprague-Dawley rats were separated into five groups: SO, sham-operated and treated with vehicle; OP, operated and treated with vehicle; RFLE-L, operated and treated with low dose (30 mg/kg) of RFLE; RFLE-M, operated and treated with medium dose (60 mg/kg) of RFLE; and RFLE-H, operated and treated with high dose (90 mg/kg) of RFLE. Bilateral common carotid artery and hypotension were used as a modeling procedure, and the RFLE were intraorally administered for 5 days (preoperative 2 and postoperative 3 days). The rats then underwent memory tests including the novel object recognition, Y-maze, Barnes maze, and passive avoidance tests, and neuronal viability and neuroinflammation were quantified in their hippocampi. The results showed that the OP group exhibited VaD-associated memory deficits, neuronal death, and microglial activation in hippocampi, while the RFLE-treated groups showed significant attenuation in all above parameters. Next, using BV-2 microglial cells challenged with lipopolysaccharide (LPS), we evaluated the effects of RFLE in dynamics of proinflammatory mediators and the upstream signaling pathway. RFLE pretreatment significantly inhibited the LPS-induced release of nitric oxide, TNF-α, and IL-6 and upregulation of the MAPKs/NF-κB/iNOS pathway. Collectively, we suggest that RFLE can attenuate the histologic alterations and memory deficits accompanied by VaD, and these roles are, partly due to the attenuation of microglial activation.

• Nutrition Research and Practice
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• v.4 no.6
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• pp.455-461
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• 2010

The tumor microenvironment, particularly sufficient nutrition and oxygen supply, is important for tumor cell survival. Nutrition deprivation causes cancer cell death. Since apoptosis is a major mechanism of neuronal loss, we explored neuronal apoptosis in various microenvironment conditions employing neuroblastoma (NB) cells. To investigate the effects of tumor malignancy and differentiation on apoptosis, the cells were exposed to poor microenvironments characterized as serum-free, low-glucose, and hypoxia. Incubation of the cells in serum-free and low-glucose environments significantly increased apoptosis in less malignant and more differentiated N-type IMR32 cells, whereas more malignant and less differentiated I-type BE(2)C cells were not affected by those treatments. In contrast, hypoxia (1 % $O_2$) did not affect apoptosis despite cell malignancy. It is suggested that DLK1 constitutes an important stem cell pathway for regulating self-renewal, clonogenicity, and tumorigenicity. This raises questions about the role of DLK1 in the cellular resistance of cancer cells under poor microenvironments, which cancer cells normally encounter. In the present study, DLK1 overexpression resulted in marked protection from apoptosis induced by nutrient deprivation. This in vitro model demonstrated that increasing severity of nutrition deprivation and knock-down of DLK1 caused greater apoptotic death, which could be a useful strategy for targeted therapies in fighting NB as well as for evaluating how nutrient deprived cells respond to therapeutic manipulation.

• Journal of Korean Neurosurgical Society
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• v.56 no.6
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• pp.488-491
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• 2014

Objective : The purpose of this study was to investigate the prenatal hypoxic effect on the fetal brain development. Methods : We used the guinea pig chronic placental insufficiency model to investigate the effect of hypoxia on fetal brain development. We ligated unilateral uterine artery at 30-32 days of gestation (dg : with term defined as -67 dg). At 50 dg, 60 dg, fetuses were sacrificed and assigned to either the growth-restricted (GR) or control (no ligation) group. After fixation, dissection, and sectioning of cerebral tissue from these animals, immunohistochemistry was performed with NeuN antibody, which is a mature neuronal marker in the cerebral cortex. Results : The number of NeuN-immunoreactive (IR) cells in the cerebral cortex did not differ between the GR and control groups at 50 dg. However, the number of NeuN-IR cells was lesser in GR fetuses than in controls at 60 dg (p<0.05). Conclusion : These findings show that chronic prenatal hypoxia affect the number of neuron in the cerebral cortex of guinea pig fetus at 60 dg. The approach used in this study is helpful for extending our understanding of neurogenesis in the cerebral cortex, and the findings may be useful for elucidating the brain injury caused by prenatal hypoxia.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.1
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• pp.55-59
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• 2014

Dehydroevodiamine HCl (DHED) has been reported to prevent memory impairment and neuronal cell loss in a rat model with cognitive disturbance. We investigated the effect of DHED on memory impairment and behavioral abnormality caused by stress. We demonstrated that DHED can improve stress-induced memory impairments and depression-like behaviors by using open-field test, Y-maze test and forced swimming test. DHED treatment significantly recovered the decreases in the levels of neural cell adhesion molecule (NCAM) proteins caused by stress and the decreases in cell viability. Our results suggested that DHED is a potential drug candidate for neuronal death, memory impairment and depression induced by stress.

• Annals of Clinical Neurophysiology
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• v.1 no.2
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• pp.147-153
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• 1999

Hippocampal slice models can be a powerful tool to study the mechanism of partial epilepsy. Despite the loss of connection with the rest of the brain, in vitro hippocampal slice preparations allow detailed physiological and pharmacological studies, which would be impossible, in vivo. There are several methods to induce electrographic seizures on hippocampal slice models. Those are electrical pulse train stimulation, 0 $Mg^{2+}$ artificial cerebrational fluid and high concentration of extracelluar $K^+$ on bath. Among them, the electrically triggered seizure may mimic the physiological communication between neuronal populations without any deterioration of normal physiologic and chemical status of the hippocampal slice models. Presumably, such communication from hyperexcitable areas to other neuronal populations is involved in the development of epilepsy. Electrographic seizures in hippocampal slice models occur in the network of neurons that are involved in epileptic seizures in the hippocampus in vivo. Because these models have many advantages and are very valuable to research of epileptogenesis on partial epilepsy, I would like to introduce the electrophysiological methods to induce electrographic seizure or epilepsy on hippocampal slice models briefly in this paper.

• Archives of Pharmacal Research
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• v.23 no.4
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• pp.413-417
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• 2000

The effect of ischemia/reperfusion-induced neuronal damage on the memory impairment were investigated using active avoidance and Morris water maze tasks in Wistar rats. Focal ischemia was induced by 1 h occlusion of the right middle cerebral artery (MCA) of Wistar male rats. Reperfusion was induced by releasing the occlusion and restoring the blood circulation for 24 h. The acquisition and preservation memory tested by active avoidance showed a significant difference between the sham and ischemia/reperfusion group. The water maze acquisition performance was also significant difference between sham and ischemia/repefusion groups in both latency and moving distance. The infarction volume was increased by the ischemia/reperfusion. Furthermore, the cresyl violet staining of the ischemia/reperfusion brain showed severe neuronal damage (pyramidal cell loss) in the cortex in addition to the striatum lesion of brain. This study shows that pyramidal cell damage in the cortex lesion may be partially related to memorial disturbance in the ischemia/reperfusion brain injury.