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Sang Won Suh - One of the best experts on this subject based on the ideXlab platform.
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Protective Effects of Protocatechuic Acid on Seizure-Induced Neuronal Death
International journal of molecular sciences, 2018Co-Authors: Song Lee, A Ra Kho, Bo Choi, Jeong Jeong, Dae Hong, Sang Lee, Min Lee, Hong Song, Hui Choi, Sang Won SuhAbstract:Protocatechuic acid (PCA) is a type of phenolic acid found in green tea and has been shown to have potent antioxidant and anti-inflammatory properties. However, the effect of PCA on pilocarpine seizure-induced Neuronal Death in the hippocampus has not been evaluated. In the present study, we investigated the potential therapeutic effects of PCA on seizure-induced brain injury. Epileptic seizure was induced by intraperitoneal (i.p.) injection of pilocarpine (25 mg/kg) in adult male rats, and PCA (30 mg/kg) was injected into the intraperitoneal space for three consecutive days after the seizure. Neuronal injury and oxidative stress were evaluated three days after a seizure. To confirm whether PCA increases Neuronal survival and reduced oxidative injury in the hippocampus, we performed Fluoro-Jade-B (FJB) staining to detect Neuronal Death and 4-hydroxynonenal (4HNE) staining to detect oxidative stress after the seizure. In the present study, we found that, compared to the seizure vehicle-treated group, PCA administration reduced Neuronal Death and oxidative stress in the hippocampus. To verify whether a decrease of Neuronal Death by PCA treatment was due to reduced glutathione (GSH) concentration, we measured glutathione with N-ethylmaleimide (GS-NEM) levels in hippocampal neurons. A seizure-induced reduction in the hippocampal Neuronal GSH concentration was preserved by PCA treatment. We also examined whether microglia activation was affected by the PCA treatment after a seizure, using CD11b staining. Here, we found that seizure-induced microglia activation was significantly reduced by the PCA treatment. Therefore, the present study demonstrates that PCA deserves further investigation as a therapeutic agent for reducing hippocampal Neuronal Death after epileptic seizures.
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Administration of Protocatechuic Acid Reduces Traumatic Brain Injury-Induced Neuronal Death.
International journal of molecular sciences, 2017Co-Authors: Sang Hwon Lee, Bo Young Choi, Song Hee Lee, A Ra Kho, Jeong Hyun Jeong, Dae Ki Hong, Sang Won SuhAbstract:Protocatechuic acid (PCA) was first purified from green tea and has shown numerous biological activities, including anti-apoptotic, anti-inflammatory, and anti-atherosclerotic effects. The effect of PCA on traumatic brain injury (TBI)-induced Neuronal Death has not previously been evaluated. TBI is defined as damage to the brain resulting from external mechanical force, such as rapid acceleration or deceleration, impact, blast waves, or penetration by a projectile. TBI causes Neuronal Death in the hippocampus and cerebral cortex. The present study aimed to evaluate the therapeutic potential of PCA on TBI-induced Neuronal Death. Here, TBI was induced by a controlled cortical impact model using rats. PCA (30 mg/kg) was injected into the intraperitoneal (ip) space immediately after TBI. Neuronal Death was evaluated with Fluoro Jade-B (FJB) staining at 24 h after TBI. Oxidative injury was detected by 4-hydroxy-2-nonenal (4HNE), glutathione (GSH) concentration was analyzed by glutathione adduct with N-ethylmaleimide (GS-NEM) staining at 24 h after TBI, and microglial activation in the hippocampus was detected by CD11b immunohistochemistry at one week after TBI. We found that the proportion of degenerating neurons, oxidative injury, GSH depletion, and microglia activation in the hippocampus and cortex were all reduced by PCA treatment following TBI. Therefore, our study suggests that PCA may have therapeutic potential in preventing TBI-induced Neuronal Death.
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Prevention of hypoglycemia-induced Neuronal Death by minocycline
Journal of neuroinflammation, 2012Co-Authors: Seok Joon Won, Byung Hoon Yoo, Tiina M. Kauppinen, Jin Hee Kim, Min Sohn, Man-seong Park, Hyung-joo Kwon, Jialing Liu, Sang Won SuhAbstract:Diabetic patients who attempt strict management of blood glucose levels frequently experience hypoglycemia. Severe and prolonged hypoglycemia causes Neuronal Death and cognitive impairment. There is no effective tool for prevention of these unwanted clinical sequelae. Minocycline, a second-generation tetracycline derivative, has been recognized as an anti-inflammatory and neuroprotective agent in several animal models such as stroke and traumatic brain injury. In the present study, we tested whether minocycline also has protective effects on hypoglycemia-induced Neuronal Death and cognitive impairment. To test our hypothesis we used an animal model of insulin-induced acute hypoglycemia. Minocycline was injected intraperitoneally at 6 hours after hypoglycemia/glucose reperfusion and injected once per day for the following 1 week. Histological evaluation for Neuronal Death and microglial activation was performed from 1 day to 1 week after hypoglycemia. Cognitive evaluation was conducted 6 weeks after hypoglycemia. Microglial activation began to be evident in the hippocampal area at 1 day after hypoglycemia and persisted for 1 week. Minocycline injection significantly reduced hypoglycemia-induced microglial activation and myeloperoxidase (MPO) immunoreactivity. Neuronal Death was significantly reduced by minocycline treatment when evaluated at 1 week after hypoglycemia. Hypoglycemia-induced cognitive impairment is also significantly prevented by the same minocycline regimen when subjects were evaluated at 6 weeks after hypoglycemia. Therefore, these results suggest that delayed treatment (6 hours post-insult) with minocycline protects against microglial activation, Neuronal Death and cognitive impairment caused by severe hypoglycemia. The present study suggests that minocycline has therapeutic potential to prevent hypoglycemia-induced brain injury in diabetic patients.
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Prevention of hypoglycemia-induced Neuronal Death by hypothermia.
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2009Co-Authors: Byung Seop Shin, Seok Joon Won, Byung Hoon Yoo, Tiina M. Kauppinen, Sang Won SuhAbstract:Hypothermia reduces Neuronal damage after cerebral ischemia and traumatic brain injury, while hyperthermia exacerbates damage from these insults. Previously we have shown that temperature-dependent modulation of excitotoxic Neuronal Death is mediated in part by temperature-dependent changes in the synaptic release/translocation of Zn(2+). In this study, we hypothesize that brain temperature also affects hypoglycemia-induced Neuronal Death by modulation of vesicular Zn(2+) release from presynaptic terminals. To test our hypothesis, we used a rat model of insulin-induced hypoglycemia. Here we found that hypoglycemia-induced Neuronal injury was significantly affected by brain temperature, that is, hypothermia inhibited while hyperthermia aggravated Neuronal Death. To investigate the mechanism of temperature-dependent Neuronal Death after hypoglycemia, we measured zinc release/translocation, reactive oxygen species (ROS) production, and microglia activation. Here we found that hypoglycemia-induced Zn(2+) release/translocation, ROS production, and microglia activation were inhibited by hypothermia but aggravated by hyperthermia. Even when the insult was accompanied by hyperthermic conditions, zinc chelation inhibited ROS production and microglia activation. Zinc chelation during hyperthermia reduced Neuronal Death, superoxide production, and microglia activation, which was comparable to the protective effects of hypothermia. We conclude that Neuronal Death after hypoglycemia is temperature-dependent and is mediated by increased Zn(2+) release, superoxide production, and microglia activation.
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Zinc release contributes to hypoglycemia-induced Neuronal Death.
Neurobiology of disease, 2004Co-Authors: Sang Won Suh, Philippe Garnier, Koji Aoyama, Yongmei Chen, Raymond A. SwansonAbstract:Neurons exposed to zinc exhibit activation of poly(ADP-ribose) polymerase-1 (PARP-1), an enzyme that normally participates in DNA repair but promotes cell Death when extensively activated. Endogenous, vesicular zinc in brain is released to the extracellular space under conditions causing Neuronal depolarization. Here, we used a rat model of insulin-induced hypoglycemia to assess the role of zinc release in PARP-1 activation and Neuronal Death after severe hypoglycemia. Zinc staining with N-(6-methoxy-8-quinolyl)-para-toluenesulfonamide (TSQ) showed depletion of presynaptic vesicular zinc from hippocampal mossy fiber terminals and accumulation of weakly bound zinc in hippocampal CA1 cell bodies after severe hypoglycemia. Intracerebroventricular injection of the zinc chelator calcium ethylene-diamine tetraacetic acid (CaEDTA) blocked the zinc accumulation and significantly reduced hypoglycemia-induced Neuronal Death. CaEDTA also attenuated the accumulation of poly(ADP-ribose), the enzymatic product of PARP-1, in hippocampal neurons. These results suggest that zinc translocation is an intermediary step linking hypoglycemia to PARP-1 activation and Neuronal Death.
Raymond A. Swanson - One of the best experts on this subject based on the ideXlab platform.
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sequential release of nitric oxide zinc and superoxide in hypoglycemic Neuronal Death
Journal of Cerebral Blood Flow and Metabolism, 2008Co-Authors: Aaron M Hamby, Pak H Chan, Byung Seop Shin, Christian T. Sheline, Raymond A. SwansonAbstract:Oxidative stress and zinc release are both known to contribute to Neuronal Death after hypoglycemia; however, the cause–effect relationships between these events are not established. Here we found, using a rat model of profound hypoglycemia, that the Neuronal zinc release and translocation that occur immediately after hypoglycemia are prevented by the nitric oxide synthase inhibitor 7-nitroindazole but not by overexpression of superoxide dismutase-1 (SOD-1). However, overexpression of SOD-1 prevented activation of poly(ADP-ribose) polymerase-1 (PARP-1) and Neuronal Death, suggesting that zinc release is upstream of superoxide production. Accordingly, zinc-induced superoxide production was blocked in Neuronal cultures by the NADPH oxidase inhibitor apocynin and by genetic deficiency in the p47 phox subunit of NADPH oxidase. A key role for the vesicular zinc pool in this process was suggested by reduced superoxide formation and Neuronal Death in mice deficient in zinc transporter 3. Together, these findings suggest a series of events in which nitric oxide production triggers vesicular zinc release, which in turn activates NADPH oxidase and PARP-1. This sequence may also occur in other central nervous system disorders in which zinc, nitric oxide, and oxidative stress have been linked.
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hypoglycemic Neuronal Death is triggered by glucose reperfusion and activation of Neuronal nadph oxidase
Journal of Clinical Investigation, 2007Co-Authors: Aaron M Hamby, Pak H Chan, Raymond A. SwansonAbstract:Hypoglycemic coma and brain injury are potential complications of insulin therapy. Certain neurons in the hippocampus and cerebral cortex are uniquely vulnerable to hypoglycemic cell Death, and oxidative stress is a key event in this cell Death process. Here we show that hypoglycemia-induced oxidative stress and Neuronal Death are attributable primarily to the activation of Neuronal NADPH oxidase during glucose reperfusion. Superoxide production and Neuronal Death were blocked by the NADPH oxidase inhibitor apocynin in both cell culture and in vivo models of insulin-induced hypoglycemia. Superoxide production and Neuronal Death were also blocked in studies using mice or cultured neurons deficient in the p47phox subunit of NADPH oxidase. Chelation of zinc with calcium disodium EDTA blocked both the assembly of the Neuronal NADPH oxidase complex and superoxide production. Inhibition of the hexose monophosphate shunt, which utilizes glucose to regenerate NADPH, also prevented superoxide formation and Neuronal Death, suggesting a mechanism linking glucose reperfusion to superoxide formation. Moreover, the degree of superoxide production and Neuronal Death increased with increasing glucose concentrations during the reperfusion period. These results suggest that high blood glucose concentrations following hypoglycemic coma can initiate Neuronal Death by a mechanism involving extracellular zinc release and activation of Neuronal NADPH oxidase.
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astrocyte influences on ischemic Neuronal Death
Current Molecular Medicine, 2004Co-Authors: Raymond A. Swanson, Weihai Ying, Tiina M. KauppinenAbstract:Glutamate excitotoxicity,oxidative stress,and acidosis are primary mediators of Neuronal Death during ischemia and reperfusion.Astrocytes influence these processes in several ways. Glutamate uptake by astrocytes normally prevents excitotoxic glutamate elevations in brain extracellular space,and this process appears to be a critical determinant of Neuronal survival in the ischemic penumbra.Conversely,glutamate efflux from astrocytes by reversal of glutamate uptake, volume sensitive organic ion channels,and other routes may contribute to extracellular glutamate elevations.Glutamate activation of Neuronal N-methyl-D-aspartate (NMDA)receptors is modulated by glycine and D-serine:both of these neuromodulators are transported by astrocytes,and D-serine production is localized exclusively to astrocytes.Astrocytes influence Neuronal antioxidant status through release of ascorbate and uptake of its oxidized form,dehydroascorbate,and by indirectly supporting Neuronal glutathione metabolism.In addition,glutathione in astrocytes can serve as a sink for nitric oxide and thereby reduce Neuronal oxidant stress during ischemia.Astrocytes probably also influence Neuronal survival in the post-ischemic period.Reactive astrocytes secrete nitric oxide, TNF α ,matrix metalloproteinases,and other factors that can contribute to delayed Neuronal Death,and facilitate brain edema via aquaporin-4 channels localized to the astrocyte endfoot-endothelial interface.On the other hand erythropoietin,a paracrine messenger in brain,is produced by astrocytes and upregulated after ischemia.Erythropoietin stimulates the Janus kinase-2 (JAK-2)and nuclear factor-kappaB (NF-kB)signaling pathways in neurons to prevent programmed cell Death after ischemic or excitotoxic stress.Astrocytes also secrete several angiogenic and neurotrophic factors that are important for vascular and Neuronal regeneration after stroke.
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Zinc release contributes to hypoglycemia-induced Neuronal Death.
Neurobiology of disease, 2004Co-Authors: Sang Won Suh, Philippe Garnier, Koji Aoyama, Yongmei Chen, Raymond A. SwansonAbstract:Neurons exposed to zinc exhibit activation of poly(ADP-ribose) polymerase-1 (PARP-1), an enzyme that normally participates in DNA repair but promotes cell Death when extensively activated. Endogenous, vesicular zinc in brain is released to the extracellular space under conditions causing Neuronal depolarization. Here, we used a rat model of insulin-induced hypoglycemia to assess the role of zinc release in PARP-1 activation and Neuronal Death after severe hypoglycemia. Zinc staining with N-(6-methoxy-8-quinolyl)-para-toluenesulfonamide (TSQ) showed depletion of presynaptic vesicular zinc from hippocampal mossy fiber terminals and accumulation of weakly bound zinc in hippocampal CA1 cell bodies after severe hypoglycemia. Intracerebroventricular injection of the zinc chelator calcium ethylene-diamine tetraacetic acid (CaEDTA) blocked the zinc accumulation and significantly reduced hypoglycemia-induced Neuronal Death. CaEDTA also attenuated the accumulation of poly(ADP-ribose), the enzymatic product of PARP-1, in hippocampal neurons. These results suggest that zinc translocation is an intermediary step linking hypoglycemia to PARP-1 activation and Neuronal Death.
Tetsumori Yamashima - One of the best experts on this subject based on the ideXlab platform.
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Can 'calpain-cathepsin hypothesis' explain Alzheimer Neuronal Death?
Ageing research reviews, 2016Co-Authors: Tetsumori YamashimaAbstract:Neurons are highly specialized post-mitotic cells, so their homeostasis and survival depend on the tightly-regulated, continuous protein degradation, synthesis, and turnover. In neurons, autophagy is indispensable to facilitate recycling of long-lived, damaged proteins and organelles in a lysosome-dependent manner. Since lysosomal proteolysis under basal conditions performs an essential housekeeping function, inhibition of the proteolysis exacerbates level of neurodegeneration. The latter is characterized by an accumulation of abnormal proteins or organelles within autophagic vacuoles which reveal as 'granulo-vacuolar degenerations' on microscopy. Heat-shock protein70.1 (Hsp70.1), as a means of molecular chaperone and lysosomal stabilizer, is a potent survival protein that confers neuroprotection against diverse stimuli, but its depletion induces neurodegeneration via autophagy failure. In response to hydroxynonenal generated from linoleic or arachidonic acids by the reactive oxygen species, a specific oxidative injury 'carbonylation' occurs at the key site Arg469 of Hsp70.1. Oxidative stress-induced carbonylation of Hsp70.1, in coordination with the calpain-mediated cleavage, leads to lysosomal destabilization/rupture and release of cathepsins with the resultant Neuronal Death. Hsp70.1 carbonylation which occurs anywhere in the brain is indispensable for Neuronal Death, but extent of calpain activation should be more crucial for determining the cell Death fate. Importantly, not only acute ischemia during stroke but also chronic ischemia due to ageing may cause calpain activation. Here, role of Hsp70.1-mediated lysosomal rupture is discussed by comparing ischemic and Alzheimer Neuronal Death. A common Neuronal Death cascade may exist between cerebral ischemia and Alzheimer's disease.
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ca2 dependent proteases in ischemic Neuronal Death a conserved calpain cathepsin cascade from nematodes to primates
Cell Calcium, 2004Co-Authors: Tetsumori YamashimaAbstract:From rodents to primates, transient global brain ischemia is a well known cause of delayed Neuronal Death of the vulnerable neurons including cornu Ammonis 1 (CA1) pyramidal cells of the hippocampus. Previous reports using the rodent experimental paradigm indicated that apoptosis is a main contributor to such ischemic Neuronal Death. In primates, however, the detailed molecular mechanism of ischemic Neuronal Death still remains obscure. Recent data suggest that necrosis rather than apoptosis appear to be the crucial component of the damage to the nervous system during human ischemic injuries and neurodegenerative diseases. Currently, necrotic Neuronal Death mediated by Ca2+-dependent cysteine proteases, is becoming accepted to underlie the pathology of neurodegenerative conditions from the nematode Caenorhabditis elegans to primates. This paper reviews the role of cysteine proteases such as caspase, calpain and cathepsin in order to clarify the mechanism of ischemic Neuronal Death being triggered by the unspecific digestion of lysosomal proteases.
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Ca2+-dependent proteases in ischemic Neuronal Death: A conserved ‘calpain–cathepsin cascade’ from nematodes to primates
Cell Calcium, 2004Co-Authors: Tetsumori YamashimaAbstract:From rodents to primates, transient global brain ischemia is a well known cause of delayed Neuronal Death of the vulnerable neurons including cornu Ammonis 1 (CA1) pyramidal cells of the hippocampus. Previous reports using the rodent experimental paradigm indicated that apoptosis is a main contributor to such ischemic Neuronal Death. In primates, however, the detailed molecular mechanism of ischemic Neuronal Death still remains obscure. Recent data suggest that necrosis rather than apoptosis appear to be the crucial component of the damage to the nervous system during human ischemic injuries and neurodegenerative diseases. Currently, necrotic Neuronal Death mediated by Ca2+-dependent cysteine proteases, is becoming accepted to underlie the pathology of neurodegenerative conditions from the nematode Caenorhabditis elegans to primates. This paper reviews the role of cysteine proteases such as caspase, calpain and cathepsin in order to clarify the mechanism of ischemic Neuronal Death being triggered by the unspecific digestion of lysosomal proteases.
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Implication of cysteine proteases calpain, cathepsin and caspase in ischemic Neuronal Death of primates.
Progress in neurobiology, 2000Co-Authors: Tetsumori YamashimaAbstract:Although more than 8000 papers of apoptosis are published annually, there are very few reports concerning necrosis in the past few years. A number of recent studies using lower species animals have suggested that the cornu Ammonis (CA) 1 Neuronal Death after brief global cerebral ischemia occurs by apoptosis, an active and genetically controlled cell suicide process. However, the studies of monkeys and humans rather support necrosis, the calpain-mediated release of lysosomal enzyme cathepsin after ischemia conceivably contributes to the cell degeneration of CA1 neurons. This paper provides an overview of recent developments in ischemic Neuronal Death, presents the cascade of the primate Neuronal Death with particular attentions to the cysteine proteases, and also indicates selective cathepsin inhibitors as a novel neuroprotectant. Furthermore, the possible interaction of calpain, cathepsin, and caspase in the cascade of ischemic Neuronal Death is discussed.
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Postictal blockade of ischemic hippocampal Neuronal Death in primates using selective cathepsin inhibitors.
Experimental Neurology, 1999Co-Authors: Katsuhiro Tsuchiya, Yukihiko Kohda, Masaki Yoshida, Liang Zhao, Takashi Ueno, Junkoh Yamashita, Tohru Yoshioka, Eiki Kominami, Tetsumori YamashimaAbstract:Abstract This paper is to study the participation of cathepsin in ischemic Neuronal Death of the monkey hippocampal cornu ammonis (CA) 1 sector and also to clarify whether its selective inhibitor epoxysuccinyl peptides such as CA-074 and E-64c can inhibit the Neuronal Death or not. In the preceding reports, we demonstrated μ-calpain activation and subsequent rupturing of the lysosomal membrane of postischemic CA1 neurons and also increase of enzyme activity of cathepsins B and L in monkeys undergoing a complete 20-min whole brain ischemia. Here, morphological, immunohistochemical and enzymatical analyses were performed to examine the efficacy of two selective cathepsin inhibitors in the postictal blockade of delayed Neuronal Death in the monkey hippocampus. Both inhibitors could significantly decrease enzyme activities of cathepsins B and L in all hippocampal sectors. When CA-074 was intravenously administered immediately after the ischemic insult, approximately 67% of CA1 neurons were saved from delayed Neuronal Death on day 5 after ischemia. In contrast, when E-64c was similarly administered, approximately 84% of CA1 neurons were saved from delayed Neuronal Death on day 5. The surviving neurons showed mild central chromatolysis and negligible immunoreactivity for cathepsins B and L. These observations indicate that the use of cathepsin inhibitors may become novel strategy for prevention of ischemic delayed Neuronal Death in the primate hippocampus.
A Ra Kho - One of the best experts on this subject based on the ideXlab platform.
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Effects of Cerebrolysin on Hippocampal Neuronal Death After Pilocarpine-Induced Seizure.
Frontiers in neuroscience, 2020Co-Authors: Dong Hyeon Kang, Bo Young Choi, Song Hee Lee, A Ra Kho, Jeong Hyun Jeong, Dae Ki Hong, Beom Seok Kang, Min Kyu Park, Hong Ki Song, Hui Chul ChoiAbstract:Epilepsy is one of the most common and severe brain diseases. The exact cause of epilepsy is unclear. Epilepsy often occurs following brain damage, such as traumatic brain injury (TBI) and ischemia. Cerebrolysin is a porcine brain peptide that is a unique neurotropic and neuroprotective agent. Cerebrolysin has been reported to increase neuroprotective effects after TBI, ischemia, and other CNS diseases. However, the effects of cerebrolysin on seizures are not known. Therefore, this study aimed to investigate the effects of neuropeptide cerebrolysin on Neuronal Death in the hippocampus after a seizure. To confirm the effects of cerebrolysin, we used a pilocarpine-induced seizure animal model. Cerebrolysin (2.5 ml/kg, i.p., once per day for 7 days) was immediately injected after a seizure induction. After 1 week, we obtained brain tissues and performed staining to histologically evaluate the potentially protective effects of cerebrolysin on seizure-induced Neuronal Death in the hippocampus. We found that cerebrolysin decreased hippocampal Neuronal Death after a seizure. In addition, an increase in brain-derived neurotrophic factor (BDNF) was confirmed through Western blot analysis to further support our hypothesis. Therefore, the present study suggests that the administration of cerebrolysin can be a useful therapeutic tool for preventing Neuronal Death after a seizure.
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Protective Effects of Protocatechuic Acid on Seizure-Induced Neuronal Death
International journal of molecular sciences, 2018Co-Authors: Song Lee, A Ra Kho, Bo Choi, Jeong Jeong, Dae Hong, Sang Lee, Min Lee, Hong Song, Hui Choi, Sang Won SuhAbstract:Protocatechuic acid (PCA) is a type of phenolic acid found in green tea and has been shown to have potent antioxidant and anti-inflammatory properties. However, the effect of PCA on pilocarpine seizure-induced Neuronal Death in the hippocampus has not been evaluated. In the present study, we investigated the potential therapeutic effects of PCA on seizure-induced brain injury. Epileptic seizure was induced by intraperitoneal (i.p.) injection of pilocarpine (25 mg/kg) in adult male rats, and PCA (30 mg/kg) was injected into the intraperitoneal space for three consecutive days after the seizure. Neuronal injury and oxidative stress were evaluated three days after a seizure. To confirm whether PCA increases Neuronal survival and reduced oxidative injury in the hippocampus, we performed Fluoro-Jade-B (FJB) staining to detect Neuronal Death and 4-hydroxynonenal (4HNE) staining to detect oxidative stress after the seizure. In the present study, we found that, compared to the seizure vehicle-treated group, PCA administration reduced Neuronal Death and oxidative stress in the hippocampus. To verify whether a decrease of Neuronal Death by PCA treatment was due to reduced glutathione (GSH) concentration, we measured glutathione with N-ethylmaleimide (GS-NEM) levels in hippocampal neurons. A seizure-induced reduction in the hippocampal Neuronal GSH concentration was preserved by PCA treatment. We also examined whether microglia activation was affected by the PCA treatment after a seizure, using CD11b staining. Here, we found that seizure-induced microglia activation was significantly reduced by the PCA treatment. Therefore, the present study demonstrates that PCA deserves further investigation as a therapeutic agent for reducing hippocampal Neuronal Death after epileptic seizures.
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Administration of Protocatechuic Acid Reduces Traumatic Brain Injury-Induced Neuronal Death.
International journal of molecular sciences, 2017Co-Authors: Sang Hwon Lee, Bo Young Choi, Song Hee Lee, A Ra Kho, Jeong Hyun Jeong, Dae Ki Hong, Sang Won SuhAbstract:Protocatechuic acid (PCA) was first purified from green tea and has shown numerous biological activities, including anti-apoptotic, anti-inflammatory, and anti-atherosclerotic effects. The effect of PCA on traumatic brain injury (TBI)-induced Neuronal Death has not previously been evaluated. TBI is defined as damage to the brain resulting from external mechanical force, such as rapid acceleration or deceleration, impact, blast waves, or penetration by a projectile. TBI causes Neuronal Death in the hippocampus and cerebral cortex. The present study aimed to evaluate the therapeutic potential of PCA on TBI-induced Neuronal Death. Here, TBI was induced by a controlled cortical impact model using rats. PCA (30 mg/kg) was injected into the intraperitoneal (ip) space immediately after TBI. Neuronal Death was evaluated with Fluoro Jade-B (FJB) staining at 24 h after TBI. Oxidative injury was detected by 4-hydroxy-2-nonenal (4HNE), glutathione (GSH) concentration was analyzed by glutathione adduct with N-ethylmaleimide (GS-NEM) staining at 24 h after TBI, and microglial activation in the hippocampus was detected by CD11b immunohistochemistry at one week after TBI. We found that the proportion of degenerating neurons, oxidative injury, GSH depletion, and microglia activation in the hippocampus and cortex were all reduced by PCA treatment following TBI. Therefore, our study suggests that PCA may have therapeutic potential in preventing TBI-induced Neuronal Death.
Tian-ming Gao - One of the best experts on this subject based on the ideXlab platform.
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Nitric oxide as an upstream signal of p38 mediates hypoxia/reoxygenation-induced Neuronal Death.
Neuro-Signals, 2009Co-Authors: Ming Chen, Hong-yu Sun, Manas Das, Jiming Kong, Tian-ming GaoAbstract:Nitric oxide (NO) and p38 have been shown to be involved in the ischemia/hypoxia-induced Neuronal injury. In this study, we examined the activation patterns of mitogen-activated protein kinases and explored the relationship between NO and p38 in a model of hippocampal Neuronal Death induced by hypoxia/reoxygenation (H/R). p38 activity increased robustly during hypoxia and after reoxygenation, while the increase of c-Jun amino-terminal kinase and extracellular signal-related kinase activities showed mild tendency. Inhibition of p38 with SB203580 or SB202190 rescued Neuronal Death, whereas inhibition of extracellular signal-related kinases with PD98059 or c-Jun amino-terminal kinases with SP600125 offered no protection. p38 inhibitors also reduced Neuronal Death induced by the NO donor S-nitrosoglutathione. L-NAME, a nonspecific NO synthase inhibitor, blocked the p38 activation and rescued H/R-induced Neuronal Death. These results suggest that NO is an upstream signal of p38 that mediates the H/R-induced Neuronal Death.
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nitric oxide as an upstream signal of p38 mediates hypoxia reoxygenation induced Neuronal Death
Neurosignals, 2009Co-Authors: Ming Chen, Hong-yu Sun, Manas Das, Jiming Kong, Tian-ming GaoAbstract:Nitric oxide (NO) and p38 have been shown to be involved in the ischemia/hypoxia-induced Neuronal injury. In this study, we examined the activation patterns of mitogen-activated protein kinases and explored the relationship between NO and p38 in a model of hippocampal Neuronal Death induced by hypoxia/reoxygenation (H/R). p38 activity increased robustly during hypoxia and after reoxygenation, while the increase of c-Jun amino-terminal kinase and extracellular signal-related kinase activities showed mild tendency. Inhibition of p38 with SB203580 or SB202190 rescued Neuronal Death, whereas inhibition of extracellular signal-related kinases with PD98059 or c-Jun amino-terminal kinases with SP600125 offered no protection. p38 inhibitors also reduced Neuronal Death induced by the NO donor S-nitrosoglutathione. L-NAME, a nonspecific NO synthase inhibitor, blocked the p38 activation and rescued H/R-induced Neuronal Death. These results suggest that NO is an upstream signal of p38 that mediates the H/R-induced Neuronal Death.