• Journal of The Korean Society of Clinical Toxicology
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• v.17 no.2
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• pp.66-78
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• 2019

Purpose: Thallium (TI+) autometallography is often used for the imaging of neuronal metabolic activity in the rodent brain under various pathophysiologic conditions. The purpose of this study was to apply a thallium autometallographic technique to observe changes in neuronal activity in the forebrain of rats following acute carbon monoxide (CO) intoxication. Methods: In order to induce acute CO intoxication, adult Sprague-Dawley rats were exposed to 1100 ppm of CO for 40 minutes, followed by 3000 ppm of CO for 20 minutes. Animals were sacrificed at 30 minutes and 5 days after induction of acute CO intoxication for thallium autometallography. Immunohistochemical staining and toluidine blue staining were performed to observe cellular damage in the forebrain following intoxication. Results: Acute CO intoxication resulted in significant reduction of TI+ uptake in major forebrain structures, including the cortex, hippocampus, thalamus, and striatum. In the cortex and hippocampal CA1 area, marked reduction of TI+ uptake was observed in the cell bodies and dendrites of pyramidal neurons at 30 minutes following acute CO intoxication. There was also strong uptake of TI+ in astrocytes in the hippocampal CA3 area following acute CO intoxication. However, there were no significant histological findings of cell death and no reduction of NeuN (+) neuronal populations in the cortex and hippocampus at 5 days after acute CO intoxication. Conclusion: The results of this study suggest that thallium autometallography can be a new and useful technique for imaging functional changes in neural activity of the forebrain structure following mild to moderate CO intoxication.

• Biomolecules & Therapeutics
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• v.29 no.3
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• pp.321-330
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• 2021

Oxidative stress plays a crucial role in the development of neuronal disorders including brain ischemic injury. Thioredoxin 1 (Trx1), a 12 kDa oxidoreductase, has anti-oxidant and anti-apoptotic functions in various cells. It has been highly implicated in brain ischemic injury. However, the protective mechanism of Trx1 against hippocampal neuronal cell death is not identified yet. Using a cell permeable Tat-Trx1 protein, protective mechanism of Trx1 against hydrogen peroxide-induced cell death was examined using HT-22 cells and an ischemic animal model. Transduced Tat-Trx1 markedly inhibited intracellular ROS levels, DNA fragmentation, and cell death in H2O2-treatment HT-22 cells. Tat-Trx1 also significantly inhibited phosphorylation of ASK1 and MAPKs in signaling pathways of HT-22 cells. In addition, Tat-Trx1 regulated expression levels of Akt, NF-κB, and apoptosis related proteins. In an ischemia animal model, Tat-Trx1 markedly protected hippocampal neuronal cell death and reduced astrocytes and microglia activation. These findings indicate that transduced Tat-Trx1 might be a potential therapeutic agent for treating ischemic injury.

• Korean Journal of Acupuncture
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• v.22 no.3
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• pp.137-156
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• 2005

Objectives : Cnidium officinale(CO) has been used for medication for stroke in the Oriental Medicine. So this study was planned to investigate the effects of CO on the focal ischemia-induced by Middle Cerebral Artery Occlusion(MCAO) in rats Materials and methods : The focal ischemia was induced by MCAO. CO extracts through oral administration and herbal acupuncture at GB2l was carried out during 3 weeks after focal ischemia-induced. Eight-arm radial maze was used for the behavioral task. For the neuroprotective effect of CO, we investigated AchE, ChAT, and NGF-expression by immnohistochemical method. Results : The error rate in the eight-arm radial maze task was significantly decreased in normal group compared to control group on 1-6days, OA-CO1(CO oral administration, 0.8g/kg) group on 1-6days, OA-CO2(CO oral administration, 1.6g/kg) group on 1-3,5,6days, HA-CO1(CO herbal acupuncture, 0.016g/kg) group on 2,3,6days, HA-CO2(CO herbal acupuncture, 0.008g/kg) group on 1-3,5,6days. The rate of correct choice was significantly increased in OA-CO1, HA-CO2. The density of neurons in the hippocampal CA1 was the most increased in OA-CO1, HA-CO1, HA-CO2. The density of ChAT in the hippocampal CA1 was increased in OA-CO1, HA-CO2. The density of ChAT in the hippocampal CA1 was significantly increased in OA-CO1, HA-CO2. The density of NGE in the hippocampal CAI was significantly increased in OA-CO1, OA-CO2, HA-CO2. Conclusions : These results suggest that CO oral administration with 0.8g/kg and CO herbal acupuncture with 0.008g/kg might be used as a regulator of cell death of cholinergic system induced by stroke.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.1
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• pp.15-21
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• 2013

Aspirin (acetylsalicylic acid) is one of the most widely used therapeutic agents based on its pharmacological actions, including anti-inflammatory, analgesic, anti-pyretic, and anti-thrombotic effects. In this study, we investigated the effects of aspirin on seizure susceptibility and hippocampal neuropathology following pilocarpine-induced status epilepticus (SE). SE was induced by pilocarpine hydrochloride (280 mg/kg, i.p.) administration in C57BL/6 mice (aged 8 weeks). Aspirin was administered daily (15 mg/kg or 150 mg/kg, i.p.) for 10 days starting 3 days before SE, continuing until 6 days after SE. After pilocarpine injection, SE onset time and mortality were recorded. Neuronal cell death was examined using cresyl violet and Fluoro-Jade staining, and glial responses were observed 7 days post SE using immunohistochemistry. In the aspirin-treated group, the onset time of SE was significantly shortened and mortality was markedly increased compared to the control group. However, in this study, aspirin treatment did not affect SE-induced neuronal cell death or astroglial and microglial responses in the hippocampus. In conclusion, these results suggest that the safety of aspirin should be reevaluated in some patients, especially with neurological disorders such as temporal lobe epilepsy.

• Journal of electromagnetic engineering and science
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• v.15 no.3
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• pp.123-128
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• 2015

Previously, we investigated extremely low-frequency magnetic fields (ELF-MFs) on diverse DNA damage responses, such as phosphorylated H2AX (${\gamma}H2AX$), comet tail moments, and aneuploidy production in several non-tumorigenic epithelial or fibroblast cell lines. However, the effect of ELF-MF on DNA damage responses in neuronal cells may not be well evaluated. Here, we investigated the effects of ELF-MF on the DNA damage responses in HT22 non-tumorigenic mouse neuronal cells. Exposure to a 60-Hz, 2 mT ELF-MF did not produce any increased ${\gamma}H2AX$ expression, comet tail moments, or aneuploidy formation. However, 2 mT ELF-MF transiently increased the cell number. From the results, ELF-MF could affect the DNA damage responses differently, depending on the cell lines.

• Journal of the Korean Society of Food Culture
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• v.36 no.6
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• pp.633-639
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• 2021

Raphanus sativus var. hortensis f. raphanistroides Makino (Korean wild radish [WR]) are root vegetables belonging to the Brassicaceae family. These radish species mostly grow in sea areas in Asia, where they have been traditionally used as a medicinal food to treat various diseases. To investigate the effect of WR on neuronal cell death in SH-SY5Y cells, beta-amyloid was used to develop the cell death model. WR attenuated neuronal cell death in SH-SY5Y and regulated the mitogen-activated protein kinase (MAPK) signaling. WR extract also inhibited acetylcholinesterase inhibitor activity. Additionally, the WR treatment group ameliorated the behavior of the memory-impaired mice in a scopolamine-induced mouse model. In the behavior test, WR treated mice showed shorter escape latency and swimming distance and improved the platform-crossing number and the swimming time within the target quadrant. Furthermore, WR prevented histological loss of neurons in hippocampal CA1 regions induced by scopolamine. This study shows that WR can prevent memory impairment which may be a crucial way for the prevention and treatment of memory dysfunction and neuronal cell death.

• The Journal of Internal Korean Medicine
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• v.25 no.3
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• pp.461-472
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• 2004

Objectives : For the screening of neuroprotective effects of medicinal herbs, the complex system of animal models suffer some disadvantages in controlling critical parameters such as blood pressure and body temperature. Additionally, application of drugs to the appropriate brain area sometimes is difficult, due to poor permeability though the blood brain barrier, and so potential protective effects might be masked. Methods : Organotypic hippocampal slice culture (OHSC) method has the advantages of being relatively easy to prepare and of maintaining the general structure, including tissue integrity and the connections between cells. Drugs can easily be applied and neuronal damage can easily be quantified by using tissues and culture media. This study demonstrates neuroprotective effects of Puerariae radix (葛根, PR), Salviae miltiorrhizae radix (丹蔘, SR), Rhei rhizoma (大黃, RR), and Bupleuri radix (柴胡, BR). These were screenedand compared to MK-801, antagonist of NMDA receptors, by using OHSC of 1 week-old Sprague-Dawley rats. Oxygen/glucose deprivation (OGD) were conducted in an anaerobic chamber $(85%\;N_2,\;10%\;CO_2\;and\;5%\;H_2)$ in a deoxygenated glucose-free medium for 60 minutes. Water extracts of each herbs were treated to culture media with $5\;{\mu}g/ml$ for 48 hours. Results : Neuronal cell death in the cultures was monitored by densitometric measurements of the cellular uptake of propidium iodide (PI). PI fluorescence images were obtained at 48 hours after the OGD and medicinal herb treatment. Also TUNEL-positive cells in the CAI and DG regions and LDH concentrations in culture media were measured at 48 hours after the OGD. According to measured data, MK-801, PR, SR and BR demonstrated significant neuroprotective effect against excessive neuronal cell death and apoptosis induced by the OGD insult. Especially, PR revealed similar neuroprotective effect to MK-801 and RR demonstrated weak neuroprotective effect. Conclusions : These results suggest that OHSC can be a suitable method for screening of neuroprotective effects of medicinal herbs. (This work was supported by the research program of Dongguk University and Grant 01-PJ9-PG1-01CO03-0003 from Ministry of Health & Welfare.)

• Journal of Life Science
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• v.15 no.3 s.70
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• pp.505-512
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• 2005

Excitotoxicity and epileptogenesis have often been associated with glutamate receptor activation. Accumulating evidences indicates that topiramate (TPM), an antiepileptic drug with multiple mechanisms of action has neuroprotective activity. We explored the neuroprotective effect of TPM on the status epilepticus (SE)-induced hippocampal neuronal death. After development of SE by kainite injection (15 mg/Kg), rats were treated with TPM (10mg/kg) for 1 week. The neuronal death was detected by Apop tag in situ detection kit, and the expression levels of glutamate receptors were semi-quantitatively analyzed by immunoblot. Kainate-induced SE caused a significant neuronal death and cell loss in CAI and CA3 regions of hippocampus at 1 week. However, treatment of TPM for 1 week after SE markedly reduced hippocampal neuronal death. The expression of N-methyl-D-aspartate (NMDA) receptor subunit 1, was increased by SE, but was not affected by 1 week treatment of TPM. The expressions of NMDA receptor subunit 2a and 2b were not changed by either SE or TPM. As for ${\alpha}-amino-3-hydroxy-5-methyl-4-isoxazole-propionate$ (AMPA) glutamate receptors (GluR), kainate-induced SE markedly up-regulated GluR1 expression but down-regulated GluR2 expression, leading to increased formation of $Ca^{2+}$ permeable GluR2- lacking AMPA receptors. TPM administration for 1 week attenuated SE-induced expression of both the up-regulation of GluR1 and down-regulation of GluR2, reversing the ratio of GluR1/GluR2 to the control value. In conclusion, TPM protects neuronal cell death against glutamate induced excitotoxicity in kainate-induced SE model, supporting the potential of TPM as a neuroprotective agent.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.2
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• pp.374-380
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• 2009

Samryungbaikchul-san(SRBCS) has been used in oriental medicine for the treatments of gastrointestinal and neurological disorders. Here, potential protective function of SRBCS was investigated in neural tissues in Alzheimer's disease(AD) mouse model. In primary cultured cells from the spinal cord of newborn rats, treatment of ${\beta}$-amyloid peptide elevated cell counts positive to glial fibrillary acidic protein(GFAP) or caspase 3 immunoreactivity, but the co-treatment of SRBCS reduced positive cell counts. In vivo administration of scopolamine, an inhibitor of muscarinic receptor, resulted in increases in the number of glial fibrillary acidic protein(GFAP) and caspase 3-positive cells in hippocampal subfields, which was then decreased by the treatment of SRBCS or acetylcholinesterase inhibitor galathamine. The present data suggest that SRBCS may play a protective role in damaged neural tissues caused by scopolamine treatments in mice.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.185.1-185.1
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• 2003

In this study, we investigated the effect of cadmium on genes expression related to zinc homeostasis in HT22 hippocampal neuron cell line by RT -PCR and western blotting technics. In the time-course effect, cadmium up-regulated the relative levels of MT -I and MT -II to~b-actin at 4 hr after treatment. These effects were consistent with MT -I/II protein contents by western blot analysis. But MT -III, a specific MT isoform in brain, was not affected by cadmium. (omitted)