Neuroprotection in stroke in the mouse with intravenous erythropoietin-Trojan horse fusion protein.

作者: Ailing Fu , Eric Ka-Wai Hui , Jeff Zhiqiang Lu , Ruben J. Boado , William M. Pardridge

DOI: 10.1016/J.BRAINRES.2010.10.097

关键词:

摘要: Erythropoietin (EPO) is a potential new treatment for acute stroke. However, EPO does not cross the blood-brain barrier (BBB). has been re-engineered as an IgG-EPO fusion protein, where fused to heavy chain of chimeric monoclonal antibody (MAb) against mouse transferrin receptor (TfR), which designated cTfRMAb-EPO protein. The able penetrate BBB following intravenous (IV) administration owing transport on TfR. In present study, neuroprotective properties alone and protein IV injection were investigated in permanent middle cerebral artery occlusion (MCAO) model adult mouse. Following MCAO, mice treated with low (1000 U/kg) high (10,000 doses recombinant EPO, or (0.05 mg/kg) (1.0 Hemispheric stroke volume neural deficit scores quantitated 24h after MCAO. There was no reduction either dose 1.0 mg/kg hemispheric reduced 81% 78%. These studies demonstrate degrees neuroprotection when neurotrophin enable across administration.

参考文章(13)
Hiroshi Kamiyama, Kumi Miura, Yukio Kato, Akira Okazaki, Kenji Kumaki, Yuichi Sugiyama, Motohiro Kato, Pharmacokinetics of Erythropoietin in Genetically Anemic Mice Drug Metabolism and Disposition. ,vol. 26, pp. 126- 131 ,(1998)
M. Sakanaka, T.-C. Wen, S. Matsuda, S. Masuda, E. Morishita, M. Nagao, R. Sasaki, In vivo evidence that erythropoietin protects neurons from ischemic damage. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 95, pp. 4635- 4640 ,(1998) , 10.1073/PNAS.95.8.4635
Myriam Bernaudin, Hugo H. Marti, Simon Roussel, Didier Divoux, André Nouvelot, Eric T. MacKenzie, Edwige Petit, A Potential Role for Erythropoietin in Focal Permanent Cerebral Ischemia in Mice Journal of Cerebral Blood Flow and Metabolism. ,vol. 19, pp. 643- 651 ,(1999) , 10.1097/00004647-199906000-00007
Feng Zhang, Armando P. Signore, Zhigang Zhou, Suping Wang, Guodong Cao, Jun Chen, Erythropoietin protects CA1 neurons against global cerebral ischemia in rat: potential signaling mechanisms. Journal of Neuroscience Research. ,vol. 83, pp. 1241- 1251 ,(2006) , 10.1002/JNR.20816
Maria A. Catania, Maria C. Marciano, Alessandra Parisi, Alessio Sturiale, Michele Buemi, Giovanni Grasso, Francesco Squadrito, Achille P. Caputi, Gioacchino Calapai, Erythropoietin prevents cognition impairment induced by transient brain ischemia in gerbils European Journal of Pharmacology. ,vol. 437, pp. 147- 150 ,(2002) , 10.1016/S0014-2999(02)01292-X
Ailing Fu, Eric Ka-Wai Hui, Jeff Zhiqiang Lu, Ruben J. Boado, William M. Pardridge, Neuroprotection in experimental stroke in the rat with an IgG–erythropoietin fusion protein Brain Research. ,vol. 1360, pp. 193- 197 ,(2010) , 10.1016/J.BRAINRES.2010.09.009
Ruben J. Boado, Eric Ka-Wai Hui, Jeff Zhiqiang Lu, William M. Pardridge, Drug Targeting of Erythropoietin Across the Primate Blood-Brain Barrier with an IgG Molecular Trojan Horse Journal of Pharmacology and Experimental Therapeutics. ,vol. 333, pp. 961- 969 ,(2010) , 10.1124/JPET.109.165092
William A Banks, Nelson L Jumbe, Catherine L Farrell, Michael L Niehoff, Anne C Heatherington, None, Passage of erythropoietic agents across the blood–brain barrier: a comparison of human and murine erythropoietin and the analog darbepoetin alfa European Journal of Pharmacology. ,vol. 505, pp. 93- 101 ,(2004) , 10.1016/J.EJPHAR.2004.10.035
Hannelore Ehrenreich, Karin Weissenborn, Hilmar Prange, Dietmar Schneider, Christian Weimar, Katja Wartenberg, Peter D. Schellinger, Matthias Bohn, Harald Becker, Martin Wegrzyn, Peter Jähnig, Manfred Herrmann, Michael Knauth, Mathias Bähr, Wolfgang Heide, Armin Wagner, Stefan Schwab, Heinz Reichmann, Günther Schwendemann, Reinhard Dengler, Andreas Kastrup, Claudia Bartels, Recombinant Human Erythropoietin in the Treatment of Acute Ischemic Stroke Stroke. ,vol. 40, ,(2009) , 10.1161/STROKEAHA.109.564872