• The Korean Journal of Physiology and Pharmacology
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• v.21 no.6
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• pp.579-589
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• 2017

Anesthetics are used extensively in surgeries and related procedures to prevent pain. However, there is some concern regarding neuronal degeneration and cognitive deficits arising from regular anesthetic exposure. Recent studies have indicated that brain-derived neurotrophic factor (BDNF) and cyclic AMP response element-binding protein (CREB) are involved in learning and memory processes. Genistein, a plant-derived isoflavone, has been shown to exhibit neuroprotective effects. The present study was performed to examine the protective effect of genistein against isoflurane-induced neurotoxicity in rats. Neonatal rats were exposed to isoflurane (0.75%, 6 hours) on postnatal day 7 (P7). Separate groups of rat pups were orally administered genistein at doses of 20, 40, or 80 mg/kg body weight from P3 to P15 and then exposed to isoflurane anesthesia on P7. Neuronal apoptosis was detected by TUNEL assay and FluoroJade B staining following isoflurane exposure. Genistein significantly reduced apoptosis in the hippocampus, reduced the expression of proapoptotic factors (Bad, Bax, and cleaved caspase-3), and increased the expression of Bcl-2 and Bcl-xL. RT-PCR analysis revealed enhanced BDNF and TrkB mRNA levels. Genistein effectively upregulated cAMP levels and phosphorylation of CREB and TrkB, leading to activation of cAMP/CREB-BDNF-TrkB signaling. PI3K/Akt signaling was also significantly activated. Genistein administration improved general behavior and enhanced learning and memory in the rats. These observations suggest that genistein exerts neuroprotective effects by suppressing isoflurane-induced neuronal apoptosis and by activating cAMP/CREB-BDNF-TrkB-PI3/Akt signaling.

• Korean Journal of Pharmacognosy
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• v.42 no.3
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• pp.276-281
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• 2011

Oxidative stress or the accumulation of reactive oxygen species (ROS) leads neuronal cellular death and dysfunction, and it contributes to neuronal degenerative disease such as Alzheimer's disease, Parkinson's disease and stroke. Glutamate-induced oxidative injury contributes to neuronal degeneration in many central nervous system (CNS) diseases, such as epilepsy and ischemia. Heme oxygenase-1 (HO-1) enzyme plays an important role of cellular antioxidant system against oxidant injury. The expression of HO-1 has cytoprotective effects in glutamate-induced oxidative cytotoxicity in HT22 cells. The induction of HO-1 is primarily regulated at the transcriptional level, and its induction by various inducers is related to the nuclear transcription factor-E2-related factor 2 (Nrf2). Nrf2 is a master regulator of the antioxidant response. NNMBS008, the water-insoluble fraction of the 70% EtOH extract of roots of Sophora flavescens, showed dominant neuroprotective effects on glutamate-induced neurotoxicity in mouse hippocampal HT22 cells by induced the expression of HO-1 and increased HO activity. In mouse hippocampal HT22 cells, NNMBS008 makes the nuclear accumulation of Nrf2 pathway. In conclusion, the waterinsoluble fraction of the 70% EtOH extract of roots of S. flavescens (NNMBS008) significantly protect glutamate-induced oxidative damage by induction of HO-1 via Nrf2 pathway in mouse hippocampal HT22 cells. These results suggest that these extracts could be the effective candidates for the treatment of ROS-related neurological diseases.

• Journal of Korean Neurosurgical Society
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• v.30 no.6
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• pp.688-698
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• 2001

Objectives : Parkinson's disease is a well-known neurodegenerative disease characterized by dopaminergic cell death in the substantia nigra. The reactive gliosis by activated astrocytes and microglias is no more regarded as a simple sequel of neuronal cell death. Microglial activation takes place in a stereotypic pattern with graded morphologic and functional(resting, activated and phagocytic) changes. In Parkinson's disease animal model, the degree of microglial activation along the nigro-striatal dopaminergic tract has not been studied intensively. The purpose of this study was to elucidate the characteristics of microglial reaction and to grade its degree of activation at substantia nigra and corpus striatum using 6-hydroxydopamine induced rat model of Parkinson's disease. Methods : Using Sprague-Dawley rat, parkinsonian model was made by 6-hydroxydopamine(OHDA) induced destruction of medial and lateral substantia nigra(SN). The rat was sacrificed 3-, 5-, 7-, 14- and 21-day-after operation. For control group, we injected saline with same manner and sacrificed 3-day after operation. With immunohistochemistry, we examined dopaminergic neuronal cells and microglial expression using tyrosine hydroxylase (TH) and OX-42 antibodies, respectively. Also we performed in situ hybridization for osteopontin, a possible marker of subset in activated microglia. Results : 1) In lesioned side of substantia nigra and corpus striatum, the TH immunoreactivity was markedly decreased in whole experimental groups. 2) Using optical densitometry, microglia induced immunoreactivity of OX-42 was counted at SN and corpus striatum. At SN, it was increased significantly on the lesioned side in control and all time-dependent experimental groups. At striatum, it was increased significantly in post lesion 3-day group only(p <0.05). Compared to control group, immunoreactivity of OX-42 on lesioned side was increased in groups, except post lesion 21-day group, at SN. Only post lesion 3-day group showed significance at striatum(p <0.05). Compared to SN region, immunoreactivity of OX-42 was much weaker in striatum. 3) Microscopically, the microglias showed typically different activation pattern. At SN, numerous phagocytic microglias were found at pars compacta and reticularis of lesion side. At striatum, no phagocytic form was found and the intensity of staining was much weaker. 4) At SN, the immunoreactivity of osteopontin showed definite laterality and it was markedly increased at pars compacta of lesion side with relatively short duration time. At striatum, however, it was not detected by in situ hybridization technique. Conclusion : The nigral 6-OHDA induced rat model of Parkinson's disease revealed several characteristic patterns of microglial reaction. At SN, microglias was activated shortly after direct neuronal damage and maintained for about three weeks. In contrast, despite of sufficient dopaminergic insufficiency at striatum, activation of microglias was trivial, and distinguished 3 day later. Antegrade slow neuronal degeneration is major pathophysiology in striatal dopaminergic deficiency. So, the acuteness of neuronal damage and consequential degree of neuronal degeneration may be important factor for microglial activation in neurodegenerative diseases such as Parkinson's disease. Additionally, osteopontin may be a possible marker for several subsets of activated microglia, possibly the phagocytic form.

• The Journal of Korean Medicine
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• v.29 no.5
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• pp.29-40
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• 2008

Objectives : It has been reported that Sophorae Subprostratae Radix (SSR) has a neuroprotective effect on cerebral ischemia in animals. In the present study, the authors investigated the neuroprotective effect of SSR on glutamate excitotoxicity. Glutamate excitotoxicity was induced by using NMDA, AMPA, and KA in PC12 cells and in organotypic hippocampal slice cultures. Methods :Methanolic extract of SSR was added at 0.5, 5, and 50 ${\mu}$g/ml to culture media for 24 hours. The effects of SSR were evaluated by measuring of cell viability, PI-stained neuronal cell death, TUNEL-positive cells, and MAP-2 immunoreactivity. Results : SSR increased PC12 cell viabilities significantly against AMPA-induced excitotoxicity, but not against NMDA-induced or KA-induced excitotoxicity. In organotypic hippocampal slice cultures damaged by NMDA-induced excitotoxicity, SSR attenuated neuronal cell death significantly in the CA1, CA3, and DG hippocampal regions and reduced TUNEL-positive cells significantly in CA1 and DG regions. In organotypic hippocampal slice cultures damaged by AMPA-induced excitotoxicity, SSR attenuated neuronal cell death and reduced TUNEL-positive cell numbers significantly in the CA1 and DG regions. In organotypic hippocampal slice cultures damaged by KA-induced excitotoxicity, SSR attenuated neuronal cell death significantly in CA3, but did not reduce TUNEL-positive cell numbers in CA1, CA3 or DG. In organotypic hippocampal slice cultures damaged by NMDA-induced excitotoxicity, SSR attenuated pyramidal neuron neurite retraction and degeneration in CA1. Conclusions : These results suggest that the neuroprotective effects of SSR are related to antagonistic effects on the NMDA and AMPA receptors of neuronal cells damaged by excitotoxicity and ischemia.

• Natural Product Sciences
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• v.13 no.3
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• pp.268-271
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• 2007

Glutamate-induced oxidative injury contributes to neuronal degeneration in many central nervous system (CNS) diseases, such as epilepsy and ischemia. Bioassay-guided fractionation of the MeOH extract of the seeds of Alpinia katsumadai Hayata (Zingiberaceae) furnished three phenolic compounds, alpinetin (1), pinocembrin (2), and (+)-catechin (3). Compounds 2 and 3 showed the potent neuroprotective effects on glutamate-induced neurotoxicity and reactive oxygen species (ROS) generation in the mouse hippocampal HT22 cells. In addition, Compounds 2 and 3 showed significant DPPH free radical scavenging effect. These results suggest that compounds 2 and 3 could be the effective candidates for the treatment of ROS-related neurological diseases.

• Korean Journal of Biological Psychiatry
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• v.2 no.2
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• pp.157-168
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• 1995

The neuropsychiatric sequelae of traumatic brain unjury(TBI) are effects on complex aspect of behavior, cognition and emotional expression. They include psychiatric disorders such as depression, psychosis, personality change, dementia, and postconcussion syndrome. The damage is done not only to the cortex of the brain but also to subcortical and axial structures. The diffuse degeneration of cerebral white mailer is axonal damage that is caused by mechanical forces shearing the neuronal fiber at the moment of impact(diffuse axonal injury, DAI). The DAI and the changed receptor-agonist mechanism ore the most important mechanisms in genesis of neuropsychiatric sequalae by mild TBI. The most important instrument for diagnosis of neuropsychiatric sequalae of TBI is a physician or psychiatrist with experience and knowledge. The most effective therapeutic tool is a professional who understands the nature of the problem.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.291-291
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• 1994

Ibotonic acid와 FeCl$_3$ 투여군은 phosphate buffered saline을 투여한 대조군에 비해 흰쥐의 능동적 회피학습 습득율을 감소시켰고 해마영역의 과산화지질 형성도를 유의하게 증가시켰으며 acetylcholinesterase의 활성을 감소시켰으나 acetylcholine의 농도에는 별영향을 주지 못하였다. 이들 약물은 신경세포 지질막등에 작용하여 노인성 치매에서와 유사한 cholinergic신경계통에 neuronal degeneration을 유발하여 학습능력 감소를 유발한 것으로 보인다. 4,결론 중추 Cholinergic성 신경계활성의 변화와 뇌내 과산화지질의 과다 형성이 학습능력 감소 및 노인성치매의 원인이라고 말할수는 없지만 이러한 뇌내의 변화률이 치매과정과 연관성을 갖는 것으로 보여진다.

• Korean Journal of Veterinary Research
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• v.38 no.2
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• pp.290-296
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• 1998

Histological changes was investigated in the 4 weeks old rat brain using NMDA (N-methyl-D-asparate) which is capable of mediating excitotoxic events. The changes were occured when the injected NMDA solved in PBS was over $1.0{\mu}g/g$(about 90nM). The necrosis of Purkinje cells in cerebellum and the increasement of coloidal plexus cell number were prevalent. The Purkinje cell number of necrosis were increased according to increasement of amount of injected NMDA. In spite of increasement of degenerated Purkinje cell number, differentiation of new Purkinje cell was not identified because total number of Purkinje cell was not changed. The change of cell number was observed in coloidal plexus cell rather than degeneration of cell. About 5 time increasement was occured. This change may cause increasement of cerebrospinal fluid and the makes mophorogy of brain more round than nomal.

• Proceedings of the Korean Society of Postharvest Science and Technology of Agricultural Products Conference
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• 2007.11a
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• pp.65-72
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• 2007

Phytochemicals have long been known to hold a number of physiological benefits, including antioxidant, anticardiovascular activities and anticancer. The profitable effects of phytochemicals from food sources such as vegetables and fruits, with respect to neurodegeneration, are only beginning to receive increased attention. Alzheimer's disease (AD) is one of the major neurodegenerative diseases for which no treatment is available, and characterized by loss of cognition and memory. Many recent studies show that the brain of AD patient is subjected to increased oxidative stress resulting from free radical damage, and the resulting cellular malfunctions are widely believed to be responsible for neuronal degeneration in AD. In this study, the relative relation between AD and phytochemicals were surveyed.

• Korean Journal of Veterinary Service
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• v.27 no.1
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• pp.63-73
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• 2004

The present experiment was carried out to study the pathogenesis of Newcastle disease(ND), ND virus (NDV) antigens and genes in various organs from NDV inoculated chickens were detected by immunohistochemistry and RT-PCR. Immunohistochemically, NDV antigens were detected in the spleen, thymus, cecal tonsil, proventriculus, trachea and lungs at 12 hour post-inoculation (hpi). Viral antigens were localized mainly in the cytoplasm of lymphocytes and macrophages. After 48 hpi, clinical findings of the affected chickens were open-mouth breathing, conjunctivitis, watery diarrhea and edema around the eye and neck. After 72 hpi, chickens showed muscular tremor, paralysis of the legs and wings, and coma. Histopathological results consist of multi-focal necrosis with hemorrhages in lymphoid aggregates of the intestinal tracts, necrosis of the lymphoid tissues, neuronal degeneration and necrosis, and perivascular cuffing. Using RT-PCR, virus genes were detected in the spleen and proventriculus at 48 hpi, and in the brain at 60 hpi.