Erythropoietin crosses the blood-brain barrier to protect against experimental brain injury.
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 approximately 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.
Brines
M L
ML
The Kenneth S. Warren Laboratories, 765 Old Saw Mill River Road, Tarrytown, NY 10591, USA. mbrines@kswl.org
Ghezzi
P
P
Keenan
S
S
Agnello
D
D
de Lanerolle
N C
NC
Cerami
C
C
Itri
L M
LM
Cerami
A
A
D000818:Animals; D001710:Biotin / Q000378:metabolism; D001812:Blood-Brain Barrier; D001930:Brain Injuries / Q000517:prevention & control*; D004921:Erythropoietin / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018696:Neuroprotective Agents / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D017467:Receptors, Erythropoietin / Q000378:metabolism; D011994:Recombinant Proteins; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control
D018696:Neuroprotective Agents; D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D004921:Erythropoietin; D001710:Biotin; D007608:Kainic Acid