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Reduced functional deficits, neuroinflammation, and secondary tissue damage after treatment of stroke by nonerythropoietic erythropoietin derivatives

Reduced functional deficits, neuroinflammation, and secondary tissue damage after treatment of stroke by nonerythropoietic erythropoietin derivatives

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VILLA, Pia, Johan van BEEK, Anna Kirstine LARSEN, Jens GERWIEN, Søren CHRISTENSEN, Anthony CERAMI, Michael BRINES, Marcel LEIST, Pietro GHEZZI, Lars TORUP, 2007. Reduced functional deficits, neuroinflammation, and secondary tissue damage after treatment of stroke by nonerythropoietic erythropoietin derivatives. In: Journal of Cerebral Blood Flow & Metabolism. 27(3), pp. 552-563. ISSN 0271-678X. Available under: doi: 10.1038/sj.jcbfm.9600370

@article{Villa2007Reduc-7277, title={Reduced functional deficits, neuroinflammation, and secondary tissue damage after treatment of stroke by nonerythropoietic erythropoietin derivatives}, year={2007}, doi={10.1038/sj.jcbfm.9600370}, number={3}, volume={27}, issn={0271-678X}, journal={Journal of Cerebral Blood Flow & Metabolism}, pages={552--563}, author={Villa, Pia and Beek, Johan van and Larsen, Anna Kirstine and Gerwien, Jens and Christensen, Søren and Cerami, Anthony and Brines, Michael and Leist, Marcel and Ghezzi, Pietro and Torup, Lars} }

Gerwien, Jens Brines, Michael Christensen, Søren Larsen, Anna Kirstine 2011-03-24T17:33:10Z Gerwien, Jens Cerami, Anthony application/pdf Torup, Lars Villa, Pia deposit-license Larsen, Anna Kirstine Reduced functional deficits, neuroinflammation, and secondary tissue damage after treatment of stroke by nonerythropoietic erythropoietin derivatives Villa, Pia Ghezzi, Pietro Beek, Johan van Journal of Cerebral Blood Flow & Metabolism ; 27 (2007). - S. 552-563 2011-03-24T17:33:10Z Ghezzi, Pietro Cerami, Anthony eng Carbamylerythropoietin (CEPO) does not bind to the classical erythropoietin (EPO) receptor. Nevertheless, similarly to EPO, CEPO promotes neuroprotection on the histologic level in short-term stroke models. In the present study, we investigated whether CEPO and other nonerythropoietic EPO analogs could enhance functional recovery and promote long-term histologic protection after experimental focal cerebral ischemia. Rats were treated with the compounds after focal cerebral ischemia. Animals survived 1, 7, or 60 days and underwent behavioral testing (sensorimotor and foot-fault tests). Brain sections were stained and analyzed for Iba-1, myeloperoxidase, Tau-1, CD68 (ED1), glial fibrillary acidic protein (GFAP), Fluoro-Jade B staining, and overall infarct volumes. Treatment with CEPO reduced perifocal microglial activation (P< 0.05), polymorphomonuclear cell infiltration (P< 0.05), and white matter damage (P < 0.01) at 1 day after occlusion. Carbamylerythropoietin- treated rats showed better functional recovery relative to vehicle-treated animals as assessed 1, 7, 14, 28, and 50 days after stroke. Both GFAP and CD68 were decreased within the ipsilateral thalamus of CEPO-treated animals 60 days postoperatively (P < 0.01 and P < 0.05, respectively). Furthermore, behavioral analysis showed efficacy of CEPO treatment even if administered 24 h after the stroke. Other nonerythropoietic derivatives such as carbamylated darbepoetin alfa and the mutant EPO-S100E were also found to protect against ischemic damage and to improve postischemic neurologic function. In conclusion, these results show that postischemic intravenous treatment with nonerythropoietic EPO derivatives leads to improved functional recovery, which may be linked to their long-term effects against neuroinflammation and secondary tissue damage. Brines, Michael Leist, Marcel Torup, Lars Beek, Johan van 2007 Christensen, Søren Leist, Marcel

Dateiabrufe seit 01.10.2014 (Informationen über die Zugriffsstatistik)

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