Erythropoietin and erythropoietin receptor in human ischemic/hypoxic brain

Using immunohistochemistry, expression of erythropoietin (EPO), a hypoxia-i nducible neuroprotective factor, and its receptor (EPOR) were investigated in human brain tissue after ischemia/hypoxia. Autopsy brains of neuropathol ogically normal subjects were compared to those with ischemic infarcts or h ypoxic damage. In normal brain, weak EPO/EPOR immunoreactivity was mainly n euronal. In fresh infarcts, EPO immunoreactivity appeared in vascular endot helium, EPOR in microvessels and neuronal fibers. In older infarcts reactiv e astrocytes exhibited EPO/EPOR immunoreactivity. Acute hypoxic brain damag e was associated with vascular EPO expression, older hypoxic damage with EP O/EPOR immunoreactivity in reactive astrocytes. The pronounced up-regulatio n of EPO/EPOR in human ischemic/hypoxic brains underlines their role as an endogenous neuroprotective system and suggests a novel therapeutic potentia l in cerebrovascular disease for EPO, a clinically well-characterized and s afe compound.