RGD Reference Report - TNFR1 upregulation mediates tolerance after brain ischemic preconditioning. - Rat Genome Database
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TNFR1 upregulation mediates tolerance after brain ischemic preconditioning.

Authors: Pradillo, Jesús M  Romera, Cristina  Hurtado, Olivia  Cárdenas, Antonio  Moro, María A  Leza, Juan C  Dávalos, Antoni  Castillo, José  Lorenzo, Pedro  Lizasoain, Ignacio 
Citation: Pradillo JM, etal., J Cereb Blood Flow Metab. 2005 Feb;25(2):193-203. doi: 10.1038/sj.jcbfm.9600019.
RGD ID: 13825261
Pubmed: (View Article at PubMed) PMID:15647744
DOI: Full-text: DOI:10.1038/sj.jcbfm.9600019

A short ischemic event (ischemic preconditioning (IPC)) can result in subsequent resistance to severe ischemic injury (ischemic tolerance (IT)). The expression and neuroprotective role of tumor necrosis factor (TNF-alpha) have been described in models of IPC and we have showed the participation of its processing enzyme, the TNF-alpha convertase enzyme (TACE) in this process. We have now decided to explore the expression and localization of TNF receptors (TNFR) as well as other signalling mechanisms involved in IT. A period of 10 mins of temporary middle cerebral artery occlusion (tMCAO) was used for focal IPC. To evaluate the ability of IPC to produce IT, permanent MCAO was performed 48 hours after IPC. Ischemic preconditioning produced a reduction in infarct volume, as we showed previously. Ischemic preconditioning caused upregulation of neuronal TNFR1 that was reduced by the selective TACE inhibitor BB1101. Intracerebral administration of TNFR1 antisense oligodeoxynucleotide, which caused a reduction in TNFR1 expression, inhibited the IPC-induced protective effect, showing that TNFR1 upregulation is implicated in IT. Moreover, treatment with BB1101, TNFR1 antisense and lactacystin-a specific proteasome inhibitor-blocked IPC-induced NF-kappaB. Immunohistochemical studies showed the expression of TACE and TNFR1 in neurons. In summary, these data show that IPC produces neuronal upregulation of TACE and TNFR1, and that the pathway TACE/TNF-alpha/TNFR1/NF-kappaB is involved in IT.


Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Tnf  (tumor necrosis factor)
Tnfrsf1a  (TNF receptor superfamily member 1A)

Genes (Mus musculus)
Tnf  (tumor necrosis factor)
Tnfrsf1a  (tumor necrosis factor receptor superfamily, member 1a)

Genes (Homo sapiens)
TNF  (tumor necrosis factor)
TNFRSF1A  (TNF receptor superfamily member 1A)

Additional Information