• The Korean Journal of Physiology and Pharmacology
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• v.12 no.3
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• pp.89-94
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• 2008

In order to reproduce chronic cerebral hypoperfusion as it occurs in human aging and Alzheimer's disease, we introduced permanent, bilateral occlusion of the common carotid arteries (BCCAO) in rats (Farkas et al, 2007). Here, we induced BCCAO in two different rat strains in order to determine whether there was a strain difference in the pathogenic response to BCCAO. Male Wistar and Sprague-Dawley (SD) rats (250-270 g) were subjected to BCCAO for three weeks. Kluver-Barrera and cresyl violet staining were used to evaluate white matter and gray matter damage, respectively. Wistar rats had a considerably higher mortality rate (four of 14 rats) as compared to SD rats (one of 15 rats) following BCCAO. Complete loss of pupillary light reflex occurred in all Wistar rats that survived, but loss of pupillary light reflex did not occur at all in SD rats. Moreover, BCCAO induced marked vacuolation in the optic tract of Wistar rats as compared to SD rats. In contrast, SD rats showed fewer CA1 hippocampal neurons than Wistar rats following BCCAO. These results suggest that the neuropathological process induced by BCCAO takes place in a region-specific pattern that varies according to the strain of rat involved.

• 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.

• Journal of Life Science
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• v.26 no.12
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• pp.1458-1465
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• 2016

We investigated the neuroprotective effect of an ethanol extract from Asparagus cochinchinensis (AC) against glutamate-induced toxicity in the HT22 hippocampal cell, which is an ideal in vitro model for oxidative stress. The neuroprotective effects of AC in HT22 cells were evaluated by analyzing cell viability, lactate dehydrogenase (LDH), flow cytometry for cell death types, reactive oxygen species (ROS), mitochondria membrane potential (MMP), and Western blot assays. In the cell death analysis, AC treatment resulted in significantly attenuated glutamate-induced loss of cell viability with a decrease in LDH release. AC treatment also reduced glutamate-induced apoptotic cell death. In the ROS and MMP analysis, AC treatment inhibited the elevation of intracellular ROS induced by glutamate exposure and the disruption of MMP. In oxidative stress-related proteins analysis, AC treatment inhibited the expression of poly ADP ribose polymerase and heme oxygenase-1 by glutamate. These results indicate that AC exerts a significant neuroprotective effect against glutamate-induced hippocampal damage by decreasing ROS production and stabilizing MMP. Thus, AC potentially provides a new strategy for the treatment of oxidative stress-related diseases.

• Journal of Ginseng Research
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• v.44 no.3
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• pp.490-495
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• 2020

Background: Ginsenoside Rk1, a saponin component isolated from heat-processed Panax ginseng Meyer, has been implicated in the regulation of antitumor and anti-inflammatory activities. Although our previous studies have demonstrated that ginsenoside Rg3 significantly attenuated the activation of NMDA receptors (NMDARs) in hippocampal neurons, the effects of ginsenosides Rg5 and Rk1, which are derived from heat-mediated dehydration of ginsenoside Rg3, on neuronal NMDARs have not yet been elucidated. Methods: We examined the regulation of NMDARs by ginsenosides Rg5 and Rk1 in cultured rat hippocampal neurons using fura-2-based calcium imaging and whole-cell patch-clamp recordings. Results: The results from our investigation showed that ginsenosides Rg3 and Rg5 inhibited NMDARs with similar potencies. However, ginsenoside Rk1 inhibited NMDARs most effectively among the five compounds (Rg3, Rg5, Rk1, Rg5/Rk1 mixture, and protopanaxadiol) tested in cultured hippocampal neurons. Its inhibition is independent of the NMDA- and glycine-binding sites, and its action seems to involve in an interaction with the polyamine-binding site of the NMDAR channel complex. Conclusion: Taken together, our results suggest that ginsenoside Rk1 might be a novel component contributable to the development of ginseng-based therapeutic treatments for neurodegenerative diseases.

• 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.

• 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.

• Toxicological Research
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• v.27 no.2
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• pp.103-110
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• 2011

Lipotoxicity involves pathological alterations to cells and tissues in response to elevated fat levels in blood. Furthermore, this process can disturb both cellular homeostasis and viability. In the current study, the authors show that neural progenitor cells (NPCs) are vulnerable to high levels of palmitic acid (PA) a saturated fatty acid. PA was found to cause cell death associated with elevated reactive oxygen species (ROS) levels, and to reduce NPCs proliferation. To evaluate the lipotoxicity of PA in adult NPCs in the hippocampus, male C57BL/6 mice were divided into two groups and maintained on either a normal diet (ND) or PA-rich high fat diet (HFD) for 2 weeks. Interestingly, short-term PA-rich HFD feeding reduced the survival of newly generated cells in the hippocampal dentate gyrus and hippocampal brain-derived neurotrophic factor levels. These findings suggest PA has a potent lipotoxicity in NPCs and that a PA-rich HFD disrupts hippocampal neurogenesis.

• Proceedings of the Korean Society of Life Science Conference
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• 2006.09a
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• pp.73.1-73.1
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• 2006

• Korean Journal of Exercise Nutrition
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• v.13 no.2
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• pp.147-153
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• 2009

Effect of whole body vibration exercise on intracerebral hemorrhage in rats. Intracerebral hemorrhage is one of the most devastating types of stroke. This disease is known to cause severe neurological damage and also has a very high mortality rate. In the present study, the effects of whole body vibration exercise on memory capability and apoptotic neuronal cell death in the hippocampal CA1 region following intracerebral hemorrhage in rats were investigated. Intracerebral hemorrhage was induced by injection of collagenase into the hippocampal CA1 region using a stereotaxic instrument. The rats were divided into 5 groups: the sham-operation group, the hemorrhage-induction group, the hemorrhage-induction and 8 Hz vibration exercise group, the hemorrhage-induction and 16 Hz vibration exercise group, and the hemorrhage-induction and 24 Hz vibration exercise group. The animals in the whole body vibration exercise groups received whole body vibration at 8 Hz, 16 Hz, and 24 Hz, respectively for 30 min once a day during 14 consecutive days. In the present results, the apoptotic neuronal cell death in the hippocampal CA1 region was significantly increased following induction of intracerebral hemorrhage, resulting in memory impairment. Whole body vibration exercise suppressed hemorrhage-induced apoptosis in the hippocampal CA1 region. This suppressive effect of whole body vibration exercise also alleviated hemorrhage-induced memory impairment. Here in this study, we have shown that whole body vibration exercise inhibited intracerebral hemorrhage-induced apoptotic neuronal cell death and thus facilitated recovery of brain function following intracerebral hemorrhage.

• The Journal of Korean Academy of Sensory Integration
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• v.2 no.1
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• pp.21-32
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• 2004

Objective : Effect of treadmill exercise on hippocampal neural cell proliferation under normal conditions and alcohol intoxication conditions has been recently studied; however, this effect under sensory stimulation application has not clarified yet. In the present study, the effect of compression stimulation application on hippocampal neural cell proliferation in the dentate gyrus in normal and alcohol intoxicated rats was investigated. Methods : Experimental design: comparative investigation on number of 5-Bromo-2'-deoxyuridine(BrdU)B-positive cells in dentate gyrus 5 days after commencement. Setting: animal laboratory. Participants: male Sprague-Dawley rats of 3weeks old in age weighing $80{\pm}10gm$. Intervention: animals were randomly assigned into 4 groups; control-rest group(n=8), control-compression group(n=8), alcohol intoxication-rest group(n=8) and alcohol intoxication-compression group(n=8). Animals of the alcohol intoxicated groups were injected intraperitoneally with alcohol(2g/kg) twice per day for 3 days. All animals were injected BrdU(50mg/kg) intraperitoneally, and rats compression stimulation application groups were compressed using sphygmomanometer cuff times per day, for 5 days following alcohol administration. Measures: mean number of BrdU-positive cells in dentate gyrus was observed via immunohistochemistry. Results : Compression stimulation application significantly increased the number of BrdU-positive cells in the dentate gyrus. Also, treatment with alcohol for 3 days inhibited cell proliferation, and compression stimulation application alleviated alcohol-induced inhibition of new cell formation. Conclusion : These results suggest the possibility that compression stimulation application may help in improvement following alcohol-induced brain damaged.