Interleukin-1β exacerbates hypoxia-induced neuronal damage, but attenuates toxicity produced by simulated ischaemia and excitotoxicity in rat organotypic hippocampal slice cultures

Pringle, Ashley K.; Niyadurupola, Nuwan; Johns, Paul; Anthony, Daniel C.; Iannotti, Fausto

doi:10.1016/s0304-3940(01)01795-5

Cited by 31 publications

(19 citation statements)

References 16 publications

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“…This observation is consistent with previous studies showing that IL-1␤ can modulate diverse forms of neurodegeneration and seizure activity (Relton and Rothwell, 1992;Vezzani et al, 1999Vezzani et al, , 2000Allan and Rothwell, 2001;Dubé et al, 2005) and that low concentrations of IL-1␤ can enhance hypoxia-induced neuronal death in cultured rat hippocampal slices (Pringle et al, 2001). Regarding possible mechanisms by which low doses of IL-1␤ increase AMPA excitotoxicity, one possibility may involve the inhibition of astroglial glutamine synthetase (Huang and O'Banion, 1998) or the reduction of astroglial glutamate uptake by a mechanism involving nitric oxide production (Hu et al, 2000).…”

Section: Effects Of Il-1␤ On Ampa-mediated Neuronal Deathsupporting

confidence: 93%

“…The effects of cytokines on AMPA-mediated neuronal cell death were studied by exposing WT slice cultures to mouse recombinant IL-1␤ (R & D Systems, London, UK) or mouse or human recombinant TNF-␣ (mouse sequence; R & D Systems; human sequence, Abingdon Peprotech, London, UK) using the following temporal sequences: preincubation for 24 h only before adding 8 M AMPA, preincubation plus coincubation with AMPA, or only coincubation with AMPA (see Fig. 1 B) (Wilde et al, 2000;Pringle et al, 2001). The same protocols were used to study the effect of anti-TNF-␣ antibody (Upstate Biotechnology, Lake Placid, NY) and IL-1ra (R & D Systems).…”

Section: Methodsmentioning

confidence: 99%

“…The same protocols were used to study the effect of anti-TNF-␣ antibody (Upstate Biotechnology, Lake Placid, NY) and IL-1ra (R & D Systems). Anti-TNF-␣ antibody was used at 81 g/ml or 162 g/ml to neutralize the biological effects of 1 ng/ml or 10 ng/ml TNF-␣, respectively (in agreement with the instruction of the supplier), whereas IL-1ra was given in a ratio of 10:1 to IL-1␤ concentrations (Pringle et al, 2001). We also performed a dose-response study (0.3-30 ng/ml) for either cytokines, applying the experimental protocol that allowed us to observe neurotoxic and/or neuroprotective effects against AMPA-mediated cell death.…”

Section: Methodsmentioning

confidence: 99%

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Modulator Effects of Interleukin-1β and Tumor Necrosis Factor-α on AMPA-Induced Excitotoxicity in Mouse Organotypic Hippocampal Slice Cultures

Bernardino¹,

Xapelli²,

Silva³

et al. 2005

J. Neurosci.

201

169

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The inflammatory cytokines interleukin-1␤ and tumor necrosis factor-␣ (TNF-␣) have been identified as mediators of several forms of neurodegeneration in the brain. However, they can produce either deleterious or beneficial effects on neuronal function. We investigated the effects of these cytokines on neuronal death caused by exposure of mouse organotypic hippocampal slice cultures to toxic concentrations of AMPA. Either potentiation of excitotoxicity or neuroprotection was observed, depending on the concentration of the cytokines and the timing of exposure. A relatively high concentration of mouse recombinant TNF-␣ (10 ng/ml) enhanced excitotoxicity when the cultures were simultaneously exposed to AMPA and to this cytokine. Decreasing the concentration of TNF-␣ to 1 ng/ml resulted in neuroprotection against AMPA-induced neuronal death independently on the application protocol. By using TNF-␣ receptor (TNFR) knock-out mice, we demonstrated that the potentiation of AMPA-induced toxicity by TNF-␣ involves TNF receptor-1, whereas the neuroprotective effect is mediated by TNF receptor-2. AMPA exposure was associated with activation and proliferation of microglia as assessed by macrophage antigen-1 and bromodeoxyuridine immunohistochemistry, suggesting a functional recruitment of cytokineproducing cells at sites of neurodegeneration. Together, these findings are relevant for understanding the role of proinflammatory cytokines and microglia activation in acute and chronic excitotoxic conditions.

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Section: Effects Of Il-1␤ On Ampa-mediated Neuronal Deathsupporting

confidence: 93%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Modulator Effects of Interleukin-1β and Tumor Necrosis Factor-α on AMPA-Induced Excitotoxicity in Mouse Organotypic Hippocampal Slice Cultures

Bernardino¹,

Xapelli²,

Silva³

et al. 2005

J. Neurosci.

201

169

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“…Taken together, these data suggest that the observed expression levels of the cytokines TNF-·, TNF-ß and IL-1ß as such play a minor role in the induction of the neuronal damage. In line with this observation, there is evidence that IL-1ß has neurotoxic effects in an injured brain, whereas this cytokine has no effects when administered to healthy brain tissue [34][35][36]. However, it has also been shown in previous studies that inhibition of TNF-· or administration of IL-1 receptor antagonist can result in reduced neuronal damage in brain tissue subjected to HI [24,26].…”

Section: Discussionmentioning

confidence: 74%

Inhibition of nNOS and iNOS following Hypoxia-Ischaemia Improves Long-Term Outcome but Does Not Influence the Inflammatory Response in the Neonatal Rat Brain

Tweel

Peeters-Scholte²,

Bel³

et al. 2002

Dev Neurosci

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In this study, we tested the hypothesis that combined inhibition of nNOS and iNOS will reduce neuronal damage and the inflammatory response induced by perinatal hypoxia-ischaemia (HI). In 12-day-old rats, HI was induced by right carotid artery occlusion followed by 90 min of 8% O₂. Immediately upon reoxygenation, the rats were treated with NOS inhibitors (n = 24) or placebo (n = 24). Neuropathology was scored at 6 weeks after HI on a 4-point scale (n = 12 per group). The expression of heat shock protein 70 (HSP70) and mRNA expression for cytokines were measured 12 h after HI (n = 12 per group). Histopathological analysis showed that the ipsilateral hemisphere in the NOS inhibition group was less damaged than in the placebo group (p < 0.05). HI induced a significant increase in HSP70 levels (p < 0.05) in the ipsilateral hemispheres, which tended to be lower in the NOS inhibition group (p = 0.07). HI induced an increase in mRNA expression for IL-1β, TNF-α and TNF-β, but there was no difference between the ipsi- and contralateral hemispheres. Combined inhibition of nNOS and iNOS did not induce any change in cytokine expression. We conclude that the long-term neuroprotective effects of combined nNOS and iNOS inhibition were not achieved by an altered cytokine response.

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“…However, there are conflicting data regarding the ability of pro-inflammatory cytokines to induce neurotoxicity. Both in vivo and in vitro studies have provided data suggesting that IL-1ß may exacerbate neuronal damage induced by hypoxic, ischemic, excitotoxic or traumatic injury (Rothwell and Luheshi, 2000;Pringle et al, 2001). In contrast, higher concentrations of IL-1ß (10-500 ng/ml) have been reported to be neuroprotective in vitro against neurodegeneration induced by oxygen/glucose deprivation (Pringle et al, 2001) as well as following excitotoxic insults (Strijbos and Rothwell, 1995).…”

Section: Introductionmentioning

confidence: 99%

The vitamin-E analog trolox and the NMDA antagonist MK-801 protect pyramidal neurons in hippocampal slice cultures from IL-1β-induced neurodegeneration

Radesäter¹,

Johansson

Öberg³

et al. 2003

neurotox res

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The neurotoxic effect of the pro-inflammatory cytokine interleukin (IL)-1beta was studied in monolayer cultures, obtained using roller-drum incubation of hippocampal slices from neonatal Sprague Dawley rats. Following exposure to recombinant rat IL-1beta for four days, a concentration dependent loss was observed in the number of NMDAR1 receptor subunit immunoreactive pyramidal neurons in the cultures, reaching significance at 10 ng/ml rIL-1beta. Also incubation with recombinant mouse IL-1beta caused a loss of pyramidal neurons, with a significant effect at a concentration of 30 pg/ml. The vitamin E analog trolox (30 microM) was found to exert a protective effect against the rIL-1beta induced neuronal degeneration. A neuroprotective action against rIL-1beta was also found after co-incubation with the NMDA antagonist dizocilpine (MK-801; 30 microM), while no protection was found with the GABAA mimetic clomethiazole. Hence, the pro-inflammatory cytokine IL-1beta is neurotoxic to hippocampal pyramidal neurons when studied in an in vitro system with advanced phenotypic characteristics. The neuroprotective effects exerted by trolox and MK-801 suggest that free radicals and NMDA receptor-mediated processes are involved in IL-1beta -induced neurodegeneration.

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Interleukin-1β exacerbates hypoxia-induced neuronal damage, but attenuates toxicity produced by simulated ischaemia and excitotoxicity in rat organotypic hippocampal slice cultures

Cited by 31 publications

References 16 publications

Modulator Effects of Interleukin-1β and Tumor Necrosis Factor-α on AMPA-Induced Excitotoxicity in Mouse Organotypic Hippocampal Slice Cultures

Modulator Effects of Interleukin-1β and Tumor Necrosis Factor-α on AMPA-Induced Excitotoxicity in Mouse Organotypic Hippocampal Slice Cultures

Inhibition of nNOS and iNOS following Hypoxia-Ischaemia Improves Long-Term Outcome but Does Not Influence the Inflammatory Response in the Neonatal Rat Brain

The vitamin-E analog trolox and the NMDA antagonist MK-801 protect pyramidal neurons in hippocampal slice cultures from IL-1β-induced neurodegeneration

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