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Title

Transforming growth factor-α acting at the epidermal growth factor receptor reduces infarct volume after permanent middle cerebral artery occlusion in rats

AuthorsJusticia, Carles ; Planas, Anna M.
KeywordsStroke
Tyrosine kinase
Neuroprotection
Brain
4,5-Dianilinophthalimide
Issue Date1999
PublisherLippincott Williams & Wilkins
CitationJournal of Cerebral Blood Flow and Metabolism 19(2): 128-132 (1999)
AbstractTransforming growth factor-α (TGF-α) is a ligand for the epidermal growth factor (EGF) receptor (EGFR), and is more abundant than EGF in the brain. The authors studied whether administration of exogenous TGF-α into the brain can protect neurons against ischemia in a model of permanent middle cerebral artery (MCA) occlusion in the rat, and whether any effect of TGF-α was mediated by EGFR by administering 4,5-dianilinophthalimide (DAPH), a protein-tyrosine kinase inhibitor with high selectivity for EGFR. Rats received either TGF-α (10 or 25 ng), DAPH (100 ng), DAPH plus TGF-α (25 ng), or vehicle in the ipsilateral first ventricle. Drugs were administered twice: 30 minutes before and 30 minutes after MCA occlusion, and infarct volume was evaluated 24 hours later. Transforming growth factor-α at the dose of 25 ng caused a statistically significant reduction of infarct volume (60%) in relation to ischemic rats administered vehicle. This reduction was no longer seen when TGF-α was administered in combination with DAPH. The present results show that TGF-α can protect neurons from ischemic damage, and that this effect is mediated by EGFR. It is suggested that activation of EGFR-mediated intracellular signalling pathways contributes to the survival of neural cells susceptible to ischemic injury.
Publisher version (URL)http://dx.doi.org/10.1097/00004647-199902000-00002
URIhttp://hdl.handle.net/10261/116856
DOI10.1097/00004647-199902000-00002
Identifiersdoi: 10.1097/00004647-199902000-00002
issn: 0271-678X
Appears in Collections:(IIBB) Artículos
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