Tissue protection depends on upregulation of the TPR. (A) Rat spinal cord does not express high levels of EPOR, as estimated by immunocytochemistry. However, within a few hours after a 1-min compression of the spinal cord at level thoracic 3 (T3), EPOR immunoreactivity more than quadruples (± SEM). (B) AsialoEPO is a tissue-protective molecule derived by removing the terminal sialic acids of the oligosaccharide chains of EPO, which results in a circulating half-life of only ∼2 min in vivo. However, tissue-protective activity of asialoEPO is similar to that of EPO. AsialoEPO (50 µg/kg) administered intraperitoneally 24 h before a 1-min compression at T3 in rats is associated with little protection, as assessed by a motor score derived by the area under the curve (AUC) for weekly measurements carried out to 28 d. In contrast, when asialoEPO was administered immediately after release of compression, there was a significant improvement in the motor score compared with control animals (± SEM; drawn from data presented in (87)).