Release of TNFα in the rat hippocampus following epileptic seizures and excitotoxic neuronal damage

Bock, Frédéric de; Dornand, Jacques; Rondouin, G.

doi:10.1097/00001756-199604260-00004

Cited by 118 publications

(68 citation statements)

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“…Seizures induced by kainate injections into amygdala result in Х 12-fold upregulation of Molecular Psychiatry TNF␣ ir in both hippocampal hemispheres in 2 days. 30 These data indicate that epileptic seizures upregulate IL-1 and TNF␣ expression. Thus, upregulation of IL-1/TNF␣ expression may be elicited both systemically or centrally as in AIDS and epilepsy, respectively.…”

Section: Two Examples Of Upregulation Of Il-1 and Tnf␣ Expression: Aimentioning

confidence: 85%

“…35 However, glial cells may also initiate cytokine signal propagation after some central perturbations. For example, A␤ [25][26][27][28][29][30][31][32][33][34][35] injected into amygdala increases IL-1␤ ir first in microglia of the amygdala and later in distant hippocampal neurons. 41 This suggests that cell types propagating cytokine signals vary with the nature of the perturbation eliciting the signal.…”

Section: Centrally Elicited Cytokine Signalingmentioning

confidence: 99%

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Cytokine signals propagate through the brain

et al. 2000

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Interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF␣) are proinflammatory cytokines that are constitutively expressed in healthy, adult brain where they mediate normal neural functions such as sleep. They are neuromodulators expressed by and acting on neurons and glia. IL-1 and TNF␣ expression is upregulated in several important diseases/disorders. Upregulation of IL-1 and/or TNF␣ expression, elicited centrally or systemically, propagates through brain parenchyma following specific spatio-temporal patterns. We propose that cytokine signals propagate along neuronal projections and extracellular diffusion pathways by molecular cascades that need to be further elucidated. This elucidation is a prerequisite for better understanding of reciprocal interactions between nervous, endocrine and immune systems. Molecular Psychiatry (2000) 5, 604-615.

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Section: Two Examples Of Upregulation Of Il-1 and Tnf␣ Expression: Aimentioning

confidence: 85%

Section: Centrally Elicited Cytokine Signalingmentioning

confidence: 99%

Cytokine signals propagate through the brain

et al. 2000

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“…Also, the robust BID cleavage observed suggests upstream caspase-8 and/or death receptor pathways might next be examined in this model, since evidence for such pathways has been provided in vivo following seizures. 10,46,47 Questions remain as to whether the present in vitro studies will extrapolate to in vivo seizure models or a clinical setting. In support of this are the similarities in caspase-3 activation seen presently to that previously observed by our group following seizures in vivo 8 and in human temporal lobe resections from patients with intractable epilepsy.…”

Section: Discussionmentioning

confidence: 99%

Seizure-like activity leads to the release of BAD from 14-3-3 protein and cell death in hippocampal neurons in vitro

et al. 2003

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Seizure-induced neuronal death may involve engagement of the BCL-2 family of apoptosis-regulating proteins. In the present study we examined the activation of proapoptotic BAD in cultured hippocampal neurons following seizures induced by removal of chronic glutamatergic transmission blockade. Kynurenic acid withdrawal elicited an increase in seizure-like electrical activity, which was inhibited by blockers of AMPA (CNQX) and NMDA (MK801 and AP5) receptor function. However, only NMDA receptor antagonists inhibited calcium entry as assessed by fura-2, and cell death of hippocampal neurons. Seizures increased proteolysis of caspase-3 and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) of cells. Seizure-like activity induced dephosphorylation of BAD and the disruption of its constitutive interaction with 14-3-3 proteins. In turn, BAD dimerized with antiapoptotic BCL-Xl after seizures. However, the absence of neuroprotective effects of pathway intervention suggests that BAD may perform a reinforcement rather than instigator role in cell death following seizures in vitro.

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“…Interestingly, autoradiographic analysis of the binding of radiolabeled IL-1 to rodent brain has revealed a high density of type I receptors in neurons of the dentate gyrus (Takao et al, 1990;Ban et al, 1991), thus suggesting that IL-1␤ is synthesized in glia and then secreted in the extracellular space for interacting with its specific receptors. In this regard, a larger release of inflammatory cytokines has been described in hippocampal slices of epileptic rats (de Bock et al, 1996).…”

Section: Abstract: Bicuculline; Cytokines; Eeg; Epilepsy; Interleukimentioning

confidence: 96%

Interleukin-1β Immunoreactivity and Microglia Are Enhanced in the Rat Hippocampus by Focal Kainate Application: Functional Evidence for Enhancement of Electrographic Seizures

et al. 1999

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Using immunocytochemistry and ELISA, we investigated the production of interleukin (IL)-1␤ in the rat hippocampus after focal application of kainic acid inducing electroencephalographic (EEG) seizures and CA3 neuronal cell loss. Next, we studied whether EEG seizures per se induced IL-1␤ and microglia changes in the hippocampus using bicuculline as a nonexcitotoxic convulsant agent. Finally, to address the functional role of this cytokine, we measured the effect of human recombinant (hr)IL-1␤ on seizure activity as one marker of the response to kainate.Three and 24 hr after unilateral intrahippocampal application of 0.19 nmol of kainate, IL-1␤ immunoreactivity was enhanced in glia in the injected and the contralateral hippocampi. At 24 hr, IL-1␤ concentration increased by 16-fold ( p Ͻ 0.01) in the injected hippocampus. Reactive microglia was enhanced with a pattern similar to IL-1␤ immunoreactivity. Intrahippocampal application of 0.77 nmol of bicuculline methiodide, which induces EEG seizures but not cell loss, enhanced IL-1␤ immunoreactivity and microglia, although to a less extent and for a shorter time compared with kainate. One nanogram of (hr)IL-1␤ intrahippocampally injected 10 min before kainate enhanced by 226% the time spent in seizures ( p Ͻ 0.01). This effect was blocked by coinjection of 1 g (hr)IL-1␤ receptor antagonist or 0.1 ng of 3-((ϩ)-2-carboxypiperazin-4-yl)-propyl-1-phosphonate, selective antagonists of IL-1␤ and NMDA receptors, respectively.Thus, convulsant and/or excitotoxic stimuli increase the production of IL-1␤ in microglia-like cells in the hippocampus. In addition, exogenous application of IL-1␤ prolongs kainateinduced hippocampal EEG seizures by enhancing glutamatergic neurotransmission.

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Release of TNFα in the rat hippocampus following epileptic seizures and excitotoxic neuronal damage

Cited by 118 publications

References 0 publications

Cytokine signals propagate through the brain

Cytokine signals propagate through the brain

Seizure-like activity leads to the release of BAD from 14-3-3 protein and cell death in hippocampal neurons in vitro

Interleukin-1β Immunoreactivity and Microglia Are Enhanced in the Rat Hippocampus by Focal Kainate Application: Functional Evidence for Enhancement of Electrographic Seizures

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