Taoufik, Era, Petit, Edwige, Divoux, Didier, Tseveleki, Vivian, Mengozzi, Manuela, Roberts, Michael L., Valable, Samuel, Ghezzi, Pietro, Quackenbush, John, Brines, Michael, Cerami, Anthony and Probert, Lesley (2008) TNF receptor I sensitizes neurons to erythropoietin- and VEGF-mediated neuroprotection after ischemic and excitotoxic injury. Proceedings of the National Academy of Sciences, 105 (16). pp. 6185-6190. ISSN 0027-8424Full text not available from this repository.
CNS neurons use robust cytoprotective mechanisms to ensure survival and functioning under conditions of injury. These involve pathways induced by endogenous neuroprotective cytokines such as erythropoietin (EPO). Recently, in contrast to its well known deleterious roles, TNF has also been shown to exhibit neuroprotective properties. In the present study, we investigated the molecular mechanisms by which TNF receptor (TNFR)I mediates neuroprotection by comparing the gene expression profiles of lesioned cortex from WT and TNFRI KO mice after permanent middle cerebral artery occlusion. Several known neuroprotective molecules were identified as TNFRI targets, notably members of the Bcl-2 family, DNA repair machinery and cell cycle, developmental, and differentiation factors, neurotransmitters and growth factors, as well as their receptors, including EPO receptor (EPOR), VEGF, colony-stimulating factor receptor 1, insulin-like growth factor (IGF), and nerve growth factor (NGF). Further analysis showed that induction of EPOR and VEGF expression in primary cortical neurons after glucose deprivation (GD) largely depended on TNFRI and was further up-regulated by TNF. Also, EPO- and VEGF-induced neuroprotection against GD, oxygen-glucose deprivation, and NMDA excitotoxicity depended significantly on TNFRI presence. Finally, EPO prevented neuronal damage induced by kainic acid in WT but not TNFRI KO mice. Our results identify cross-talk between tissue protective cytokines, specifically that TNFRI is necessary for constitutive and GD-induced expression of EFOR and VEGF and for EIPO-mediated neuroprotection.
|Schools and Departments:||Brighton and Sussex Medical School > Clinical and Laboratory Investigation|
|Subjects:||Q Science > Q Science (General)|
|Depositing User:||Grecia GarciaGarcia|
|Date Deposited:||19 Aug 2011 11:33|
|Last Modified:||30 Nov 2012 16:55|
|Google Scholar:||47 Citations|