The Experts below are selected from a list of 2079 Experts worldwide ranked by ideXlab platform
Lung-sen Kao - One of the best experts on this subject based on the ideXlab platform.
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Soluble Epoxide Hydrolase Inhibition Attenuates Excitotoxicity Involving 14,15-Epoxyeicosatrienoic Acid–Mediated Astrocytic Survival and Plasticity to Preserve Glutamate Homeostasis
Molecular Neurobiology, 2019Co-Authors: Yi-min Kuo, Pei-chien Hsu, Chia-chi Hung, Ya-yu Hu, Yu-ling Gan, Chun-hua Lin, Feng-shiun Shie, Yu Jie Huang, Wen-kuei Chang, Lung-sen KaoAbstract:Astrocytes play pivotal roles in regulating glutamate homeostasis at tripartite synapses. Inhibition of soluble epoxide hydrolase (sEHi) provides neuroprotection by blocking the degradation of 14,15-epoxyeicosatrienoic acid (14,15-EET), a lipid mediator whose synthesis can be activated downstream from group 1 metabotropic glutamate receptor (mGluR) signaling in astrocytes. However, it is unclear how sEHi regulates glutamate excitotoxicity. Here, we used three primary rat cortical culture systems, neuron-enriched (NE), astrocyte-enriched glia-neuron mix (GN), and purified astrocytes, to delineate the underlying mechanism by which sEHi and 14,15-EET attenuate excitotoxicity. We found that sEH inhibitor 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) and 14,15-EET both attenuated N -methyl- D -aspartate (NMDA)-induced neurite damage and cell death in GN, not NE, cortical cultures. The anti-excitotoxic effects of 14,15-EET and AUDA were both blocked by the group 1 mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP), as were their protective effects against NMDA-disrupted perineuronal astrocyte processes expressing glutamate transporter-1 (GLT-1) and subsequent glutamate uptake. Knockdown of sEH expression also attenuated NMDA neurotoxicity in mGluR5- and GLT-1-dependent manners. The 14,15-EET/AUDA-preserved astroglial integrity was confirmed in glutamate-stimulated primary astrocytes along with the reduction of the c-Jun N-terminal kinase 1 phosphorylation, in which the 14,15-EET effect is mGluR5-dependent. In vivo studies validated that sEHi and genetic deletion of sEH ( Ephx2 -KO) ameliorated excitotoxic Kainic Acid-Induced Seizure, memory impairment, and neuronal loss while preserving GLT-1-expressing perineuronal astrocytes in hippocampal CA3 subregions. These results suggest that 14,15-EET mediates mGluR5-dependent anti-excitotoxicity by protecting astrocytes to maintain glutamate homeostasis, which may account for the beneficial effect of sEH inhibition in excitotoxic brain injury and diseases.
Sok Park - One of the best experts on this subject based on the ideXlab platform.
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Combined Low-Intensity Exercise and Ascorbic Acid Attenuates Kainic Acid-Induced Seizure and Oxidative Stress in Mice
Neurochemical Research, 2016Co-Authors: Hee-jae Kim, Wook Song, Eun Hee Jin, Jongkyu Kim, Yoonseok Chun, Sok ParkAbstract:Physical exercise and vitamins such as ascorbic acid (ASC) have been recognized as an effective strategy in neuroprotection and neurorehabilitatioin. However, there is a need to find an efficient treatment regimen that includes ASC and low-intensity exercise to diminish the risk of overtraining and nutritional treatment by attenuating oxidative stress. In the present study, we investigated the combined effect of low-intensity physical exercise (EX) and ASC on Kainic acid (KA)-induced Seizure activity and oxidative stress in mice. The mice were randomly assigned into groups as follows: “KA only” (n = 11), “ASC + KA” (n = 11), “Ex + KA” (n = 11), “ASC + Ex + KA” (n = 11). In the present study, low intensity of swimming training period lasted 8 weeks and consisted of 30-min sessions daily (three times per week) without tail weighting. Although no preventive effect of low-intensity exercise or ASC on KA Seizure occurrence was evident, there was a decrease of Seizure activity, Seizure development (latency to first Seizures), and mortality in “ASC + Ex + KA” compared to “ASC + KA”, “Ex + KA”, and “KA only” group. In addition, a preventive synergistic coordination of low-intensity exercise and ASC was evident in glutathione peroxidase and superoxide dismutase activity compared to separate treatment. These results suggest that low-intensity exercise and ASC treatment have preventive effects on Seizure activity and development with alternation of oxidative status.
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Synergic Effect of Exercise and Lipoic Acid on Protection Against Kainic Acid Induced Seizure Activity and Oxidative Stress in Mice
Neurochemical Research, 2014Co-Authors: Hee-jae Kim, Wook Song, Jin-soo Kim, Eun Hee Jin, Moon-seok Kwon, Sok ParkAbstract:Anti-convulsant effects of physical exercise and lipoic acid (LA), also referred to as thioctic acid with antioxidant activity, were investigated using chemical induced Seizure model. We investigated the synergic effect of physical exercise and LA on Kainic Acid-Induced Seizure activity caused by oxidative stress. After 8 weeks of swimming training, body weight decreased and endurance capacity increased significantly compared to sedentary mice. Kainic acid (30 mg/kg, i.p.) evoked Seizure activity 5 min after injection, and Seizure activity peaked approximately 80 min after Kainic acid treatment. Median Seizure activity score in KA only treated group was 4.55 (range 0.5–5), 3.45 for “LA + KA” group (range 0.5–4.3), 3.12 for “EX + KA” group (range 0.05–3.4, p
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Synergic effect of exercise and lipoic acid on protection against Kainic acid induced Seizure activity and oxidative stress in mice.
Neurochemical research, 2014Co-Authors: Hee-jae Kim, Wook Song, Jin-soo Kim, Eun Hee Jin, Moon-seok Kwon, Sok ParkAbstract:Anti-convulsant effects of physical exercise and lipoic acid (LA), also referred to as thioctic acid with antioxidant activity, were investigated using chemical induced Seizure model. We investigated the synergic effect of physical exercise and LA on Kainic Acid-Induced Seizure activity caused by oxidative stress. After 8 weeks of swimming training, body weight decreased and endurance capacity increased significantly compared to sedentary mice. Kainic acid (30 mg/kg, i.p.) evoked Seizure activity 5 min after injection, and Seizure activity peaked approximately 80 min after Kainic acid treatment. Median Seizure activity score in KA only treated group was 4.55 (range 0.5-5), 3.45 for "LA + KA" group (range 0.5-4.3), 3.12 for "EX + KA" group (range 0.05-3.4, p < 0.05 vs. "KA only" group), 2.13 for "EX + LA + KA" group (range 0.5-3.0, p < 0.05 vs. "EX + KA" group). Also, there was a synergic cooperation of exercise and LA in lowering the mortality in Kainic acid treated mice (χ2 = 5.45, p = 0.031; "EX + KA" group vs. "LA + EX + KA" group). In addition, the synergic effect of exercise and LA was found in PGx activity compared to separated treatment ("LA + EX + KA": 37.3 ± 1.36; p < 0.05 vs. "LA + KA" and "EX + KA" group). These results indicate that physical exercise along with LA could be a more efficient method for modulating Seizure activity and oxidative stress.
Yi-min Kuo - One of the best experts on this subject based on the ideXlab platform.
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Soluble Epoxide Hydrolase Inhibition Attenuates Excitotoxicity Involving 14,15-Epoxyeicosatrienoic Acid–Mediated Astrocytic Survival and Plasticity to Preserve Glutamate Homeostasis
Molecular Neurobiology, 2019Co-Authors: Yi-min Kuo, Pei-chien Hsu, Chia-chi Hung, Ya-yu Hu, Yu-ling Gan, Chun-hua Lin, Feng-shiun Shie, Yu Jie Huang, Wen-kuei Chang, Lung-sen KaoAbstract:Astrocytes play pivotal roles in regulating glutamate homeostasis at tripartite synapses. Inhibition of soluble epoxide hydrolase (sEHi) provides neuroprotection by blocking the degradation of 14,15-epoxyeicosatrienoic acid (14,15-EET), a lipid mediator whose synthesis can be activated downstream from group 1 metabotropic glutamate receptor (mGluR) signaling in astrocytes. However, it is unclear how sEHi regulates glutamate excitotoxicity. Here, we used three primary rat cortical culture systems, neuron-enriched (NE), astrocyte-enriched glia-neuron mix (GN), and purified astrocytes, to delineate the underlying mechanism by which sEHi and 14,15-EET attenuate excitotoxicity. We found that sEH inhibitor 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) and 14,15-EET both attenuated N -methyl- D -aspartate (NMDA)-induced neurite damage and cell death in GN, not NE, cortical cultures. The anti-excitotoxic effects of 14,15-EET and AUDA were both blocked by the group 1 mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP), as were their protective effects against NMDA-disrupted perineuronal astrocyte processes expressing glutamate transporter-1 (GLT-1) and subsequent glutamate uptake. Knockdown of sEH expression also attenuated NMDA neurotoxicity in mGluR5- and GLT-1-dependent manners. The 14,15-EET/AUDA-preserved astroglial integrity was confirmed in glutamate-stimulated primary astrocytes along with the reduction of the c-Jun N-terminal kinase 1 phosphorylation, in which the 14,15-EET effect is mGluR5-dependent. In vivo studies validated that sEHi and genetic deletion of sEH ( Ephx2 -KO) ameliorated excitotoxic Kainic Acid-Induced Seizure, memory impairment, and neuronal loss while preserving GLT-1-expressing perineuronal astrocytes in hippocampal CA3 subregions. These results suggest that 14,15-EET mediates mGluR5-dependent anti-excitotoxicity by protecting astrocytes to maintain glutamate homeostasis, which may account for the beneficial effect of sEH inhibition in excitotoxic brain injury and diseases.
Hee-jae Kim - One of the best experts on this subject based on the ideXlab platform.
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Combined Low-Intensity Exercise and Ascorbic Acid Attenuates Kainic Acid-Induced Seizure and Oxidative Stress in Mice
Neurochemical Research, 2016Co-Authors: Hee-jae Kim, Wook Song, Eun Hee Jin, Jongkyu Kim, Yoonseok Chun, Sok ParkAbstract:Physical exercise and vitamins such as ascorbic acid (ASC) have been recognized as an effective strategy in neuroprotection and neurorehabilitatioin. However, there is a need to find an efficient treatment regimen that includes ASC and low-intensity exercise to diminish the risk of overtraining and nutritional treatment by attenuating oxidative stress. In the present study, we investigated the combined effect of low-intensity physical exercise (EX) and ASC on Kainic acid (KA)-induced Seizure activity and oxidative stress in mice. The mice were randomly assigned into groups as follows: “KA only” (n = 11), “ASC + KA” (n = 11), “Ex + KA” (n = 11), “ASC + Ex + KA” (n = 11). In the present study, low intensity of swimming training period lasted 8 weeks and consisted of 30-min sessions daily (three times per week) without tail weighting. Although no preventive effect of low-intensity exercise or ASC on KA Seizure occurrence was evident, there was a decrease of Seizure activity, Seizure development (latency to first Seizures), and mortality in “ASC + Ex + KA” compared to “ASC + KA”, “Ex + KA”, and “KA only” group. In addition, a preventive synergistic coordination of low-intensity exercise and ASC was evident in glutathione peroxidase and superoxide dismutase activity compared to separate treatment. These results suggest that low-intensity exercise and ASC treatment have preventive effects on Seizure activity and development with alternation of oxidative status.
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Synergic Effect of Exercise and Lipoic Acid on Protection Against Kainic Acid Induced Seizure Activity and Oxidative Stress in Mice
Neurochemical Research, 2014Co-Authors: Hee-jae Kim, Wook Song, Jin-soo Kim, Eun Hee Jin, Moon-seok Kwon, Sok ParkAbstract:Anti-convulsant effects of physical exercise and lipoic acid (LA), also referred to as thioctic acid with antioxidant activity, were investigated using chemical induced Seizure model. We investigated the synergic effect of physical exercise and LA on Kainic Acid-Induced Seizure activity caused by oxidative stress. After 8 weeks of swimming training, body weight decreased and endurance capacity increased significantly compared to sedentary mice. Kainic acid (30 mg/kg, i.p.) evoked Seizure activity 5 min after injection, and Seizure activity peaked approximately 80 min after Kainic acid treatment. Median Seizure activity score in KA only treated group was 4.55 (range 0.5–5), 3.45 for “LA + KA” group (range 0.5–4.3), 3.12 for “EX + KA” group (range 0.05–3.4, p
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Synergic effect of exercise and lipoic acid on protection against Kainic acid induced Seizure activity and oxidative stress in mice.
Neurochemical research, 2014Co-Authors: Hee-jae Kim, Wook Song, Jin-soo Kim, Eun Hee Jin, Moon-seok Kwon, Sok ParkAbstract:Anti-convulsant effects of physical exercise and lipoic acid (LA), also referred to as thioctic acid with antioxidant activity, were investigated using chemical induced Seizure model. We investigated the synergic effect of physical exercise and LA on Kainic Acid-Induced Seizure activity caused by oxidative stress. After 8 weeks of swimming training, body weight decreased and endurance capacity increased significantly compared to sedentary mice. Kainic acid (30 mg/kg, i.p.) evoked Seizure activity 5 min after injection, and Seizure activity peaked approximately 80 min after Kainic acid treatment. Median Seizure activity score in KA only treated group was 4.55 (range 0.5-5), 3.45 for "LA + KA" group (range 0.5-4.3), 3.12 for "EX + KA" group (range 0.05-3.4, p < 0.05 vs. "KA only" group), 2.13 for "EX + LA + KA" group (range 0.5-3.0, p < 0.05 vs. "EX + KA" group). Also, there was a synergic cooperation of exercise and LA in lowering the mortality in Kainic acid treated mice (χ2 = 5.45, p = 0.031; "EX + KA" group vs. "LA + EX + KA" group). In addition, the synergic effect of exercise and LA was found in PGx activity compared to separated treatment ("LA + EX + KA": 37.3 ± 1.36; p < 0.05 vs. "LA + KA" and "EX + KA" group). These results indicate that physical exercise along with LA could be a more efficient method for modulating Seizure activity and oxidative stress.
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involvement of endogenous prostaglandin f2α on Kainic acid induced Seizure activity through fp receptor the mechanism of proconvulsant effects of cox 2 inhibitors
Brain Research, 2008Co-Authors: Hee-jae Kim, Soo Hwan Lee, Changhyun Moon, Jeein Chung, Yisook Jung, Eun Joo BaikAbstract:Abstract COX-2 and prostaglandins (PGs) might play important roles in epilepsy. In Kainic Acid-Induced Seizures, the brain largely increases PGD 2 , first from COX-1 and later COX-2-induced PGF 2α . Pre-treatment with COX-2 inhibitors such as indomethacin, nimesulide, and celecoxib is known to aggravate Kainic acid (KA)-induced Seizure activity. However it is not known whether the proconvulsant effect of those non-steroidal anti-inflammatory drugs (NSAIDs) is due to changes in endogenous prostaglandins (PGs), or what types of PGs are involved. The purpose of this study was to determine the effect of intracisternally administered PGs on KA-induced Seizures aggravated by pre- or post-treatment with COX-2 inhibitors. Systemic KA injection (10 mg/kg i.p.) in mice evoked mild Seizure activity within 15 min. PGs were administrated intracisternally 20 min prior to KA administration. COX inhibitors (indomethacin, nimesulide, and ketoprofen, 10 mg/kg i.p.) were injected 1 h before or 15 min after KA. An additional COX-2 inhibitor, celecoxib, was administered orally. Intracisternally administered PGF 2α (700 ng), but not PGD 2 (700 ng) or PGE 2 (700 ng) completely alleviated KA-induced Seizures potentiated by COX-2 inhibitors, and also reduced KA-induced hippocampal neuronal death aggravated by indomethacin. PGF 2α alone did not affect KA-induced Seizures. However, an FP receptor antagonist, AL 8810 (10 or 50 ng) which is an 11β-fluoro analogue of PGF 2α potentiated KA-induced Seizure activity dose-dependently. In summary, pre- or post-treatment with COX-2 inhibitors aggravates KA-induced Seizures, which suggests to change the endogenous PGF 2α . Seizure-induced PGF 2α might act as an endogenous anticonvulsant through FP receptors.
Chia-chi Hung - One of the best experts on this subject based on the ideXlab platform.
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Soluble Epoxide Hydrolase Inhibition Attenuates Excitotoxicity Involving 14,15-Epoxyeicosatrienoic Acid–Mediated Astrocytic Survival and Plasticity to Preserve Glutamate Homeostasis
Molecular Neurobiology, 2019Co-Authors: Yi-min Kuo, Pei-chien Hsu, Chia-chi Hung, Ya-yu Hu, Yu-ling Gan, Chun-hua Lin, Feng-shiun Shie, Yu Jie Huang, Wen-kuei Chang, Lung-sen KaoAbstract:Astrocytes play pivotal roles in regulating glutamate homeostasis at tripartite synapses. Inhibition of soluble epoxide hydrolase (sEHi) provides neuroprotection by blocking the degradation of 14,15-epoxyeicosatrienoic acid (14,15-EET), a lipid mediator whose synthesis can be activated downstream from group 1 metabotropic glutamate receptor (mGluR) signaling in astrocytes. However, it is unclear how sEHi regulates glutamate excitotoxicity. Here, we used three primary rat cortical culture systems, neuron-enriched (NE), astrocyte-enriched glia-neuron mix (GN), and purified astrocytes, to delineate the underlying mechanism by which sEHi and 14,15-EET attenuate excitotoxicity. We found that sEH inhibitor 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) and 14,15-EET both attenuated N -methyl- D -aspartate (NMDA)-induced neurite damage and cell death in GN, not NE, cortical cultures. The anti-excitotoxic effects of 14,15-EET and AUDA were both blocked by the group 1 mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP), as were their protective effects against NMDA-disrupted perineuronal astrocyte processes expressing glutamate transporter-1 (GLT-1) and subsequent glutamate uptake. Knockdown of sEH expression also attenuated NMDA neurotoxicity in mGluR5- and GLT-1-dependent manners. The 14,15-EET/AUDA-preserved astroglial integrity was confirmed in glutamate-stimulated primary astrocytes along with the reduction of the c-Jun N-terminal kinase 1 phosphorylation, in which the 14,15-EET effect is mGluR5-dependent. In vivo studies validated that sEHi and genetic deletion of sEH ( Ephx2 -KO) ameliorated excitotoxic Kainic Acid-Induced Seizure, memory impairment, and neuronal loss while preserving GLT-1-expressing perineuronal astrocytes in hippocampal CA3 subregions. These results suggest that 14,15-EET mediates mGluR5-dependent anti-excitotoxicity by protecting astrocytes to maintain glutamate homeostasis, which may account for the beneficial effect of sEH inhibition in excitotoxic brain injury and diseases.