Erythropoietin protects against brain ischemic injury by inhibition of nitric oxide formation

Erythropoietin prevents in vitro glutamate-induced neuronal death and could play a role in the central nervous system. We investigated the in vivo eff ects of recombinant human erythropoietin after intraperitoneal (i.p.; 25-10 0 U) or intracerebroventricular (i.c.v.; 0.25-25 U) administration on survi val, brain malonildialdehyde (MDA) levels, brain edema, hippocampal neurona l death and brain nitric oxide (NO) synthesis after bilateral carotid occlu sion (5 min), followed by reperfusion in the Mongolian gerbil. Peripheral p osttreatment with recombinant human erythropoietin reduced postischemic MDA levels, brain edema and increased survival. Either peripheral or i.c.v. po sttreatment with recombinant human erythropoietin significantly reduced hip pocampal CA1 neuronal loss, observed 7 days after the ischemic event. Incre ase of nitrite and nitrate (as an index of NO formation) in the hippocampus , as observed after ischemia, was reduced in animals treated with recombina nt human erythropoietin. These data suggest that in vivo recombinant human erythropoietin effects on brain ischemic injury could be due to inhibition of NO overproduction. (C) 2000 Elsevier Science B.V. All rights reserved.