Abstract
TNF-α has been reported to be relevant in stroke-induced neuronal death. However the precise function of TNF-α in brain ischemia remains controversial since there are data supporting either a detrimental or a protective effect. Here we show that TNF-α is released after oxygen-glucose deprivation (OGD) of cortical cultures and is a major contributor to the apoptotic death observed without affecting the OGD-mediated necrotic cell death. In this paradigm, apoptosis depends on TNF-α-induced activation of caspase-8 and -3 without affecting the activation of caspase-9. By using knock-out mice for TNF-α receptor 1, we show that the activation of both caspase-3 and -8 by TNF-α is mediated by TNF-α receptor 1. The pro-apoptotic role of TNF-α in OGD is restricted to neurons and microglia, since astrocytes do not express either TNF-α or TNF-α receptor 1. Altogether, these results show that apoptosis of cortical neurons after OGD is mediated by TNF-α/TNF-α receptor 1. © 2009 Elsevier Inc. All rights reserved.
Original language | English |
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Pages (from-to) | 438-447 |
Journal | Neurobiology of Disease |
Volume | 35 |
DOIs | |
Publication status | Published - 1 Jan 2009 |
Keywords
- Apoptosis
- Brain
- Caspase
- Cell culture
- Ischemia
- TNF-α