Erythropoietin crosses the blood–brain barrier to protect against experimental brain injury

Proceedings of the National Academy of Sciences of the United States of America - Tập 97 Số 19 - Trang 10526-10531 - 2000
Michael Brines1, Pietro Ghezzi1, Sonja Keenan1, Davide Agnello1, Nihal C. de Lanerolle1, A Cerami1, Loretta M. Itri1, Bruce Beutler1
1The Kenneth S. Warren Laboratories, 765 Old Saw Mill River Road, Tarrytown, NY 10591; Laboratory of Neuroimmunology, Mario Negri Institute for Pharmacological Research, Milan, Italy 20157; Department of Neurosurgery, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520; and Ortho Biotech Inc., P.O. Box 670, 700 U.S. Highway, Route 202 South, Raritan, NJ 08869-0602

Tóm tắt

Erythropoietin (EPO), recognized for its central role in erythropoiesis, also mediates neuroprotection when the recombinant form (r-Hu-EPO) is directly injected into ischemic rodent brain. We observed abundant expression of the EPO receptor at brain capillaries, which could provide a route for circulating EPO to enter the brain. In confirmation of this hypothesis, systemic administration of r-Hu-EPO before or up to 6 h after focal brain ischemia reduced injury by ≈50–75%. R-Hu-EPO also ameliorates the extent of concussive brain injury, the immune damage in experimental autoimmune encephalomyelitis, and the toxicity of kainate. Given r-Hu-EPO's excellent safety profile, clinical trials evaluating systemically administered r-Hu-EPO as a general neuroprotective treatment are warranted.

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Proceedings of the National Academy of Sciences of the United States of America

Tập 97 Số 19

10526-10531

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