Neuroprotective effects of FK506 against excitotoxicity in organotypic hippocampal slice culture

Lee, Kyung Hee; Won, Ran; Kim, Un Jeng; Kim, Ga Min; Chung, Myung-Ae; Sohn, Jong Hee; Lee, Bae Hwan

doi:10.1016/j.neulet.2010.03.009

Cited by 17 publications

(14 citation statements)

References 27 publications

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“…Low concentrations of KA result in a specific loss of CA3 neurons, while high concentrations induce complete neuronal death. In our previous study [22], we observed the same phenomenon of selective vulnerability in the CA3 region at 5 μM (low concentration) KA exposure using PI uptake, and the results of cresyl violet and TUNEL staining corresponded with the PI results. Neuronal cell death may be caused by excessive ROS, mitochondrial dysfunction and caspase activation.…”

Section: Resultssupporting

confidence: 71%

Neuroprotective Effects of α-Tocotrienol on Kainic Acid-Induced Neurotoxicity in Organotypic Hippocampal Slice Cultures

Jung

Lee

Won

et al. 2013

IJMS

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Vitamin E, such as alpha-tocopherol (ATPH) and alpha-tocotrienol (ATTN), is a chain-breaking antioxidant that prevents the chain propagation step during lipid peroxidation. In the present study, we investigated the effects of ATTN on KA-induced neuronal death using organotypic hippocampal slice culture (OHSC) and compared the neuroprotective effects of ATTN and ATPH. After 15 h KA (5 μM) treatment, delayed neuronal death was detected in the CA3 region and reactive oxygen species (ROS) formation and lipid peroxidation were also increased. Both co-treatment and post-treatment of ATPH (100 μM) or ATTN (100 μM) significantly increased the cell survival and reduced the number of TUNEL-positive cells in the CA3 region. Increased dichlorofluorescein (DCF) fluorescence and levels of thiobarbiturate reactive substances (TBARS) were decreased by ATPH and ATTN treatment. These data suggest that ATPH and ATTN treatment have protective effects on KA-induced cell death in OHSC. ATTN treatment tended to be more effective than ATPH treatment, even though there was no significant difference between ATPH and ATTN in co-treatment or post-treatment.

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Section: Resultssupporting

confidence: 71%

Neuroprotective Effects of α-Tocotrienol on Kainic Acid-Induced Neurotoxicity in Organotypic Hippocampal Slice Cultures

Jung

Lee

Won

et al. 2013

IJMS

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“…Bausch and McNamara (2004) showed that, with 48 hr of KA (6-7 lM) treatment, there is a loss of CA3 pyramidal cells and a slight decrease in the number of granule cells. We also previously reported that cultured hippocampal slices present the same phenomenon of selective vulnerability in the CA3 with low-dose (5 lM) KA treatment after prolonged culture (21-25 DIV; Kim et al, 2008;Lee et al, 2010). Moreover, we observed relatively minor injury in the CA1 region.…”

Section: Regulation Of Glycolysis Reduces the Neuronal Cell Death Indsupporting

confidence: 79%

Inhibition of hexokinase leads to neuroprotection against excitotoxicity in organotypic hippocampal slice culture

Lee

Park

Won

et al. 2010

J of Neuroscience Research

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During seizures, glucose concentrations are high in the hippocampus. Mitochondrial hexokinase (HK) catalyzes the first essential step of glucose metabolism and directly couples extramitochondrial glycolysis to intramitochondrial oxidative phosphorylation. The neuroprotective effects of an HK inhibitor, 3-bromopyruvate (3-BrPA), on kainic acid (KA)-induced excitotoxic injury were investigated. Hippocampal slices were prepared from hippocampi of 6-8-day-old rats using a tissue chopper and placed on a membrane insert. After a treatment with KA (5 μM) for 15 hr, neuronal death was quantified by propidium iodide (PI), cresol violet, and TUNEL staining. KA-induced cell death was significantly prevented by 30 μM 3-BrPA treatment. According to Western blots, the expression level of phospho-Akt increased after 3-BrPA treatment. The induction of long-term potentiation (LTP) at 48 hr after 3-BrPA treatment tended to increase in the CA1 area compared with the KA-only group, but the difference was not significant. Blocking the PI3 kinase/Akt pathway using LY294002 reversed the neuroprotective effect of 3-BrPA. These results suggest that inhibition of HK may play a protective role against neuronal death in KA-induced excitotoxic injury.

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“…In vitro studies in human neuroblastoma and glioma cells as well as rat hippocampal neurons and hepatocytes demonstrated FK's antioxidative properties are linked to increased glutathione and superoxide dismutase levels and decreased ROS production [38][39][40]. These results add to our previous work showing enhanced expression of glutathione peroxidase (an antioxidant enzyme) and decreased expression of nitrotyrosine (a marker of peroxynitrite and oxidative stress) after CNI with FK treatment [2].…”

Section: Discussionsupporting

confidence: 59%

FK506 neuroprotection After cavernous nerve injury is mediated by thioredoxin and glutathione redox systems

Lagoda¹,

Xie²,

Sezen³

et al. 2015

The Journal of Sexual Medicine

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Neuroprotective effects of FK506 against excitotoxicity in organotypic hippocampal slice culture

Cited by 17 publications

References 27 publications

Neuroprotective Effects of α-Tocotrienol on Kainic Acid-Induced Neurotoxicity in Organotypic Hippocampal Slice Cultures

Neuroprotective Effects of α-Tocotrienol on Kainic Acid-Induced Neurotoxicity in Organotypic Hippocampal Slice Cultures

Inhibition of hexokinase leads to neuroprotection against excitotoxicity in organotypic hippocampal slice culture

FK506 neuroprotection After cavernous nerve injury is mediated by thioredoxin and glutathione redox systems

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