The brain and other sites of erythropoietin production.

Ischemic hypoxia of the head induced in dogs by carotid compression produces EPO secretion, upon direct cerebral stimulation, and adaptive carotid-respiratory reflexes via sino-carotid stimulation. During hypoxic hypoxia, there also occurs extrarenal EPO production, as shown in binephrectomized rats compared to controls. Ischemic hypoxia of a single kidney transplanted in the neck area (the other kidney being removed) does not induce EPO secretion. An additional factor, of extra-renal origin, is required for the renal production of EPO in a non-hypoxic organism. Section of the spinal cord at C6 level in rats does not abolish EPO secretion induced by hypobaric hypoxia, a fact that suggests that there is no nervous center to control EPO release into a peripheral organ, but EPO might be produced in the brain itself, possibly crossing the blood-brain barrier to reach the blood flow. Stereotactical attempts to locate nervous centers of erythropoiesis regulation also failed. EPO secretion obtained by electrical stimulation of different brain areas suggests the existence of widespread secretory cells, which might be the astrocytes. EPO production along the lymph-forming territories and the involvement of the lining macrophages is reported.