• 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.

• Journal of Dental Rehabilitation and Applied Science
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• v.23 no.2
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• pp.179-186
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• 2007

The decrease of masticatory function caused by tooth loss leads to a decrease of cerebral blood flow volume resulting in impairment of cognitive function and learning memory disorder. However, the reduced mastication-mediated morphological alteration in the central nervous system (CNS) responsible for senile deficit of cognition, learning and memory has not been well documented. In this study, the effect of the loss of the molar teeth (molarless condition) on the hippocampal expression of glial fibrillary acidic protein (GFAP) protein was studied by immunohistochemical techniques. The results were as follows : 1. The molarless mice showed a lower density of pyramidal cells in the cornu ammonis 1 (CA1) and dentate gyrus (DG) region of the hippocampus than control mice. 2. Immunohistochemical analysis showed that the molarless condition enhanced the time-dependent increase in the cell density and hypertrophy of GFAP immunoreactivity in the CA1 region of the hippocampus. The molarless condition enhanced an time-dependent decrease in the number of neurons in the hippocampal formation and the time-dependent increase in the number and hypertrophy of GFAP-labeled cells in the same region. The data suggest a possible link between reduced mastication and histological changes in hippocampal formation that may be one risk factor for senile impairment of cognitive function and spatial learning memory.

• Journal of the korean academy of Pediatric Dentistry
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• v.27 no.1
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• pp.7-14
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• 2000

Inhibitory cells are critically involved in shaping normal hippocampal function and are thought to be important elements in the development of hippocampal pathologies. The present study was carried out in hippocampal CA1 area in vivo to compare with hippocampal slice studies. Intracellular and extracellular recordings with or without bicuculline electrodes were obtained in the intact brain of anesthetized rats, and cells were intracellularty labelled with neurobiotin. Electrical stimulation of fimbria-fornix resulted in an initial short-latency population spike. In the presence of $10{\mu}M$ bicuculline, orthodromic stimulation resulted in bursts of population spikes. The amplitude of population spikes in the CA1 region increased with stimulus intensity, as did the number of population spikes when the field recording electrode contained $10{\mu}M$ bicuculline. We measured the level of excitability in the CA1 area, using a paired-pulse stimulus paradigm to evoke population spikes. Population spikes showed strong paired-pulse inhibition at short interstimulus intervals. Burst afterdischarges up to 400 ms were observed after paired-pulse stimulus. These result suggest that hippocampal CA1 inhibitory interneurons can affect the excitability of pyramidal neurons that can not be appreciated in conventional in vitro preparation.

• Toxicological Research
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• v.6 no.2
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• pp.191-204
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• 1990

Trimethyltin (TMT) induced lesions in the rat hippocampal formation was reviewed. Adult rats were treated with a single dose of 6.0 mg TMT/kg b.w. and were sacrificed between 3-60 days following exposure. On the hippocampal formation, the granule cells of fascia dentata showed early changes which subsided considerably at a later time when the destruction of the pyramidal neurons of the Ammon's horn became increasingly pronounced with time, leading to severe destruction of the structure. It is interesting to note that there was an inverse relationship of pathological involvement between the f.d. granule cells and the Ammon's horn neurons; i.e., when there was a large sparing of the granule cells. there was an extensive damage to the Ammon's horn and vice versa. This inverse relationship was also true between the $CA_3$neurons and the $CA_{1,2}$neurons in the Ammon's horn. Progressive zinc loss, as demonstrated by Timm's method, on the Mossy fibers was also observed. Similar Mossy fiber zinc depletion has been demonstrated in electrical stimulatory excitation condition of the perforant path to the hippocampus. Depletion of corticosterone, an inhibitor to the hippocampal neurons, by means of adrenalectomy will exaggerate the TMT induced hippocampal lesion. Neonatal study revealed that a unique degenerative pattern of the Ammon's horn could be established in accordance with exposure to TMT at specific maturation periods of the fippocampal formation: increasing destruction of the Ammon's horn with increasing synaptogenesis between the f.d. granule cells and the Ammon's horn neurons. Thus it is apparent that the damage of the Ammon's horn, upon exposure to TMT, may depend on the integrity and functional state of the f.d. granule cells. A hyperexcitory scheme and mechanism as the toxicity basis of TMT in the hippocampal formation is proposed and discussed.

• The Korean Journal of Physiology and Pharmacology
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• v.11 no.6
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• pp.247-251
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• 2007

Changes of single unit activity of CA1 hippocampus region were investigated in anesthetized Mongolian gerbils for six days following transient ischemia. Ischemia was produced immediately before the implantation of micro-wire recording electrodes. In control animals receiving pseudo-ischemic surgery, neither spontaneous neuronal activities ($5.70{\pm}0.4Hz$) nor the number of recorded neurons per animal changed significantly for six days. Correlative firings among simultaneously recorded neurons were weak (correlation coefficient > 0.6) in the control animals. Animals subjected to ischemia exhibited a significant elevation of neural firing at post-ischemic 12 hr ($9.95{\pm}0.9Hz$) and day 1 ($8.48{\pm}0.8Hz$), but a significant depression of activity at post-ischemic day 6 ($1.84{\pm}0.3Hz$) when compared to the activities of non-ischemic control animal. Ischemia significantly (correlation coefficient > 0.6) increased correlative firings among simultaneously recorded neurons, which were prominent especially during post-ischemic days 1, 2 and 6. Although the numbers of spontaneously active neurons recorded from control group varied within normal range during the experimental period, those from ischemic group changed in post-ischemic time-dependent manner. Temporal changes of the number of cells recorded per animal between control group and ischemic group were also significantly different (p = 0.0084, t = 3.271, df = 10). Cresyl violet staining indicated significant loss of CA1 cells at post-ischemic day 7. Overall, we showed post-ischemic time-dependent, differential changes of three characteristics, including spontaneous activity, network relationship and excitability of CA1 cells, suggesting sustained neural functions. Thus, histological observation of CA1 cell death till post-ischemic day 7 may not represent actual neuronal death.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.1
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• pp.73-79
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• 2000

This study investigated whether propofol, an intravenous, non-barbiturate anesthetic, could reduce brain damage following global forebrain ischemia. Transient global ischemia was induced in gerbils by occlusion of bilateral carotid arteries for 3 min. Propofol (50 mg/kg) was administered intraperitoneally 30 min before, immediately after, and at 1 h, 2 h, 6 h after occlusion. Thereafter, propofol was administered twice daily for three days. Treated animals were processed in parallel with ischemic animals receiving 10% intralipid as a vehicle or with sham-operated controls. In histologic findings, counts of viable neurons were made in the pyramidal cell layer of the hippocampal CA1 area 4 days after ischemia. The number of viable neurons in the pyramidal cell layer of CA1 area was similar in animals treated with a vehicle or a subanesthetic dose of propofol. In terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling (TUNEL) assay, semiquantitative analysis of dark-brown neuronal cells was made in the hippocampal CA1 area. There was no significant difference in the degree of TUNEL staining in the hippocampal CA1 area between vehicle-treated and propofol-treated animals. These results show that subanesthetic dose of propofol does not reduce delayed neuronal cell death following transient global ischemia in Mongolian gerbils.

• Animal cells and systems
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• v.12 no.4
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• pp.203-209
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• 2008

Berberine, an isoquinoline alkaloid found in Coptidis Rhizoma(goldenthread) extract, has multiple pharmacological effects such as anti-inflammatory, antimicrobial and anti-ischemic effects. In the present study, we examined the effects of berberine on neuronal survival and differentiation in a hippocampal precursor cell line and in the memory deficient rat model. Berberine increased in a dose dependent manner the survival of hippocampal precursor cells as well as differentiated cells. In addition, berberine promoted neuronal differentiation of hippocampal precursor cells. In the memory deficient rat model induced by stereotaxic injection of ibotenic acid into entorhinal cortex(Ibo model), hippocampal cells were increased about 2.7 fold in the pyramidal layer of CA1 region and about 2 fold in the dentate gyrus by administration of berberine after 2 weeks of ibotenic acid injection. Furthermore, neuronal cells immunoreactive to calbindin were increased in the hippocampus and entorhinal cortex area by administration of berberine. Taken together, these results suggest that berberine has neuroprotective effect in the Ibo model rat brain by promoting the neuronal survival and differentiation.

• Journal of Integrative Natural Science
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• v.11 no.3
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• pp.139-147
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• 2018

Hippocampal atrophy is a well-established imaging biomarker of Alzheimer disease (AD). However, hippocampus is a non-homogenous structure with cytoarchitecturally and functionally distinct sub-regions or subfield, with each region performing distinct functions. Certain regions of the subfield have shown selective vulnerability to AD. Here, we are interested in studying the effects of normal aging and mild cognitive impairment on these sub-regional volumes. With a reliable automated segmentation technique, we segmented these subregions of the hippocampus in 101 cognitively normal (CN), 135 early mild cognitive impairment (EMCI), 67 late mild cognitive impairment (LMCI) and 48 AD subjects. Thereby, dividing the hippocampus into hippocampal tail (tail), subiculum (SUB), cornu ammonis 1 (CA1), hippocampal fissure (fissure), presubiculum (PSUB), parasubiculum (ParaSUB), molecular layer (ML), granule cells/molecular layer/dentate gyrus (GCMLDG), cornu ammonis 3(CA3), cornu ammonis 4(CA4), fimbria and hippocampal-amygdala transition area (HATA). In this cross sectional study of 351 ADNI subjects, no differences in terms of age, gender, and years of education were observed among the groups. Though, the groups had statistically significant differences (p < 0.05 after the multiple comparison correction) in the Mini-Mental State Examination (MMSE) scores. There was asymmetrical volume loss in the early stages of AD with the left hemisphere showing volume loss in regions that were unaffected in the right hemisphere. Bilateral parasubiculum, right cornu ammonis 1, 3 and 4, right fimbria and right HATA regions did not show any volume loss till the late MCI stages. Our findings suggest that the hippocampal subfield regions are selectively vulnerable to AD and also that these vulnerabilities are asymmetrical especially during the early stages of AD.

• Journal of Ginseng Research
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• v.33 no.4
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• pp.294-304
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• 2009

Ginsenosides are among the most well-known traditional herbal medicines frequently used for the treatment of various symptoms in South Korea. The neuroprotective effects of ginsenoside $Rg_3$ (G-$Rg_3$) on cholesterol-oxide-(CO)-induced neurotoxicity were investigated through the analyses of rat brains. The recently accumulated reports show that ginseng saponins (GTS), the major active ingredients of Panax ginseng, have protective effects against neurotoxin insults. In the present study, the neuroprotective effects of G-$Rg_3$ on CO-induced hippocampal excitotoxicity were examined in vivo. The in-vitro studies using rat cultured hippocampal neurons revealed that G-$Rg_3$ treatment significantly inhibited CO-induced hippocampal cell death. G-$Rg_3$ treatment not only significantly reduced CO-induced DNA damage but also attenuated CO-induced apoptosis. The in-vivo studies that were conducted revealed that the intracerebroventricular (i.c.v.) pre-administration of G-$Rg_3$ significantly reduced i.c.v. CO-induced hippocampal damage in rats. To examine the mechanisms underlying the in-vitro and in-vivo neuroprotective effects of G-$Rg_3$ against CO-induced hippocampal excitotoxicity, the effect of G-$Rg_3$ on the CO-induced elevations of the apoptotic cells in cultured hippocampal cells was examined, and it was found that G-$Rg_3$ treatment inhibited CO-induced apoptosis. The histopathological evaluation demonstrated that G-$Rg_3$ significantly diminished the apoptosis in the hippocampus and also spared the hippocampal CA1, CA3, and dentate gyrus neurons. G-$Rg_3$ also significantly improved the CO-caused behavioral impairment. G-$Rg_3$ itself had no effect, however, on the CO-induced inhibition of succinate dehydrogenase activity (data not shown). These results collectively indicate the G-$Rg_3$-induced neuroprotection against CO in rat hippocampus. With regard to the wide use of G-$Rg_3$, this agent is potentially beneficial in treating CO-induced brain injury.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.6
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• pp.1401-1406
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• 2007

The present study investigated neuroprotective effects Rehmanniae Radix on PC12 cells and hippocampal neural cells. PC12 cells were damage by $H_2O_2$ and nitric oxide and organotypic hippocampal slice cultures were damaged by oxygen-glucose deprivation. Then methanol extract of Rehmanniae Radix was treated with 0.5, 5, and $50\;{\mu}g/ml$ in culture media. Effects of Rehmanniae Radix were evaluated with cell viability assay, PI-staining, and TUNEL-labeling. Treatment of Rehmanniae Radix ($with\;5\;and\;50\;{\mu}g/ml$) produced significant increase of cell viability of PC12 cells damaged by $H_2O_2$ and by SNP-induced nitric oxide. Treatment of Rehmanniae Radix produced significant decrease of PI-uptake % in CA1 ($with\;5\;and\;50\;{\mu}g/ml$) and DG ($with\;50\;{\mu}g/ml$) regions of organotypic hippocampal slice cultures damaged by oxygen-glucose deprivation. Moreover, treatment of Rehmanniae Radix produced significant decrease of TUNEL- positive cells in CA1 ($with\;5\;and\;50\;{\mu}g/ml$) and DG ($with\;50\;{\mu}g/ml$) regions of organotypic hippocampal slice cultures damaged by oxygen-glucose deprivation. These results suggest that methanol extract of Rehmanniae Radix has neuroprotective effects on PC12 cells damaged by oxidative stress and on organotypic hippocampal slice cultures damaged by oxygen-glucose deprivation.