Nuclear factor kappa B-mediated kainate neurotoxicity in the rat and hamster hippocampus

Won, Seok Joon; Ko, Hyuk Wan; Kim, E.Y; Park, Eun Chan; Huh, Kyu Ha; Jung, Noh-Pal; Choi, In Hong; Oh, Yumi; Shin, Hyo-Seon; Gwag, Byoung Joo

doi:10.1016/s0306-4522(99)00196-7

Cited by 29 publications

(17 citation statements)

References 46 publications

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“…Similar patterns towards excitotoxicity or (hypoxic-) ischemic insults in the hippocampus have been observed previously both in vivo [34-38] and in vitro in organotypic slice cultures [32,39-44], corroborating our findings. Interestingly, selectivity towards NMDA has been shown to be independent of an intact hippocampal neuronal circuitry as isolated CA3, CA1 and DG slice cultures still respond with a selective vulnerability towards NMDA, with the CA1 and CA3 regions being more susceptible to NMDA than the DG region [45].…”

Section: Discussionsupporting

confidence: 92%

Neuroprotective function for ramified microglia in hippocampal excitotoxicity

Vinet

Weering

Heinrich

et al. 2012

J Neuroinflammation

224

219

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BackgroundMost of the known functions of microglia, including neurotoxic and neuroprotective properties, are attributed to morphologically-activated microglia. Resting, ramified microglia are suggested to primarily monitor their environment including synapses. Here, we show an active protective role of ramified microglia in excitotoxicity-induced neurodegeneration.MethodsMouse organotypic hippocampal slice cultures were treated with N-methyl-D-aspartic acid (NMDA) to induce excitotoxic neuronal cell death. This procedure was performed in slices containing resting microglia or slices that were chemically or genetically depleted of their endogenous microglia.ResultsTreatment of mouse organotypic hippocampal slice cultures with 10-50 μM N-methyl-D-aspartic acid (NMDA) induced region-specific excitotoxic neuronal cell death with CA1 neurons being most vulnerable, whereas CA3 and DG neurons were affected less. Ablation of ramified microglia severely enhanced NMDA-induced neuronal cell death in the CA3 and DG region rendering them almost as sensitive as CA1 neurons. Replenishment of microglia-free slices with microglia restored the original resistance of CA3 and DG neurons towards NMDA.ConclusionsOur data strongly suggest that ramified microglia not only screen their microenvironment but additionally protect hippocampal neurons under pathological conditions. Morphological activation of ramified microglia is thus not required to influence neuronal survival.

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Section: Discussionsupporting

confidence: 92%

Neuroprotective function for ramified microglia in hippocampal excitotoxicity

Vinet

Weering

Heinrich

et al. 2012

J Neuroinflammation

224

219

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show abstract

“…In addition, in this study, the results for the NF- κ B levels were inconclusive because of the inconsistent results following the 3 experiments; the levels of NF- κ B were the upstream of the pro-inflammatory cytokines IL-1 β , IL-6, and TNF- α . Previous studies have reported that the DNA-binding activity of NF- κ B increased at 24 h following KA-treatment in rat models [10, 32]. In summary, we assert that the JNKp MAPK signal pathway plays a critical role in epileptogenesis at 3 h following KA administration; therefore, UR, RP, and VA suppression of the expression of JNKp MAPk inhibit the development of epilepsy.…”

Section: Discussionsupporting

confidence: 65%

Antiepileptic Effect ofUncaria rhynchophyllaandRhynchophyllineInvolved in the Initiation of c-Jun N-Terminal Kinase Phosphorylation of MAPK Signal Pathways in Acute Seizures of Kainic Acid-Treated Rats

Hsu

Tang

Liu

et al. 2013

Evidence-Based Complementary and Alternative Medicine

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Seizures cause inflammation of the central nervous system. The extent of the inflammation is related to the severity and recurrence of the seizures. Cell surface receptors are stimulated by stimulators such as kainic acid (KA), which causes intracellular mitogen-activated protein kinase (MAPK) signal pathway transmission to coordinate a response. It is known that Uncaria rhynchophylla (UR) and rhynchophylline (RP) have anticonvulsive effects, although the mechanisms remain unclear. Therefore, the purpose of this study is to develop a novel strategy for treating epilepsy by investigating how UR and RP initiate their anticonvulsive mechanisms. Sprague-Dawley rats were administered KA (12 mg/kg, i.p.) to induce seizure before being sacrificed. The brain was removed 3 h after KA administration. The results indicate that pretreatment with UR (1.0 g/kg), RP (0.25 mg/kg), and valproic acid (VA, 250 mg/kg) for 3 d could reduce epileptic seizures and could also reduce the expression of c-Jun aminoterminal kinase phosphorylation (JNKp) of MAPK signal pathways in the cerebral cortex and hippocampus brain tissues. Proinflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor-α remain unchanged, indicating that the anticonvulsive effect of UR and RP is initially involved in the JNKp MAPK signal pathway during the KA-induced acute seizure period.

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“…NF- κ B, a major regulator of inflammation, has been linked with epilepsy in many reports. Overexpression of NF- κ B in the brain hippocampus has been observed both in the experimental models of epilepsy [32] and in hippocampus tissues surgically removed from patients with temporal lobe epilepsy [33]. Yu et al reported that NF- κ B mediated TNF-induced upregulation of mdr1 promoter activity by selectively binding p65 to mdr1 , suggesting inflammation enhances BBB efflux transport through NF- κ B activation [34].…”

Section: Discussionmentioning

confidence: 99%

Nuclear Factor-Kappa B Activity Regulates Brain Expression of P-Glycoprotein in the Kainic Acid-Induced Seizure Rats

Qin²,

Liu³

et al. 2011

Mediators of Inflammation

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This study was aimed to investigate the effect of NF-κB activity on the seizure susceptibility, brain damage, and P-gp expression in kainic acid- (KA-) induced seizure rats. Male SD rats were divided into saline control group (NS group), KA induced epilepsy group (EP group), and epilepsy group intervened with NF-κB inhibitor-pyrrolidine dithiocarbamate salt (PDTC group) or with dexamethasone (DEX group). No seizures were observed in the rats of NS group. Compared with NS group, increased P-gp expression and NF-κB activation in the rat brain of the EP group were observed after KA micro-injection. Both PDTC and DEX pre-treatment significantly increased the latency to grade III or V seizure onset compared to EP group but failed to show neuron-protective effect as the number of survival neurons didn't significantly differ from that in EP group. Furthermore, PDTC pre-treatment significantly decreased P-gp expression along with NF-κB activation in the hippocampus CA3 area and amygdala complex of rats compared with the EP group, implying that NF-κB activation involved in the seizure susceptibility and seizure induced brain P-gp over-expression. Additionally, DEX pre-treatment only decreased P-gp expression level without inhibition of NF-κB activation, suggesting NF-κB independent pathway may also participate in regulating seizure induced P-gp over-expression.

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Nuclear factor kappa B-mediated kainate neurotoxicity in the rat and hamster hippocampus

Cited by 29 publications

References 46 publications

Neuroprotective function for ramified microglia in hippocampal excitotoxicity

Neuroprotective function for ramified microglia in hippocampal excitotoxicity

Antiepileptic Effect ofUncaria rhynchophyllaandRhynchophyllineInvolved in the Initiation of c-Jun N-Terminal Kinase Phosphorylation of MAPK Signal Pathways in Acute Seizures of Kainic Acid-Treated Rats

Nuclear Factor-Kappa B Activity Regulates Brain Expression of P-Glycoprotein in the Kainic Acid-Induced Seizure Rats

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