Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0599766 (functional recovery)
 13,441 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Erythropoietin (EPO) functions as a tissue-protective cytokine in addition to its crucial hormonal role in red cell production. In the brain, for example, EPO and its receptor are locally produced, are modulated by metabolic stressors, and provide neuroprotective and antiinflammatory functions. We have previously shown that recombinant human EPO (rhEPO) administered within the systemic circulation enters the brain and is neuroprotective. At present, it is unknown whether rhEPO can also improve recovery after traumatic injury of the spinal cord. To evaluate whether rhEPO improves functional outcome if administered after cord injury, two rodent models were evaluated. First, a moderate compression of 0.6 N was produced by application of an aneurysm clip at level T3 for 1 min. RhEPO (1,000 units per kg of body weight i.p.) administered immediately after release of compression was associated with partial recovery of motor function within 12 h after injury, which was nearly complete by 28 days. In contrast, saline-treated animals exhibited only poor recovery. In the second model used, rhEPO administration (5,000 units per kg of body weight i.p. given once 1 h after injury) also produced a superior recovery of function compared with saline-treated controls after a contusion of 1 N at level T9. In this model of more severe spinal cord injury, secondary inflammation was also markedly attenuated by rhEPO administration and associated with reduced cavitation within the cord. These observations suggest that rhEPO provides early recovery of function, especially after spinal cord compression, as well as longer-latency neuroprotective, antiinflammatory and antiapoptotic functions.
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PMID:Recombinant human erythropoietin counteracts secondary injury and markedly enhances neurological recovery from experimental spinal cord trauma. 1208 84

Erythropoietin (EPO) plays an important role in the brain's response to neuronal injury. Systemic administration of recombinant human EPO (rhEPO) protects neurons from injury after middle cerebral artery occlusion, traumatic brain injury, neuroinflammation, and excitotoxicity. Protection is in part mediated by antiapoptotic mechanisms. We conducted parallel studies of rhEPO in a model of transient global retinal ischemia induced by raising intraocular pressure, which is a clinically relevant model for retinal diseases. We observed abundant expression of EPO receptor (EPO-R) throughout the ischemic retina. Neutralization of endogenous EPO with soluble EPO-R exacerbated ischemic injury, which supports a crucial role for an endogenous EPO/EPO-R system in the survival and recovery of neurons after an ischemic insult. Systemic administration of rhEPO before or immediately after retinal ischemia not only reduced histopathological damage but also promoted functional recovery as assessed by electroretinography. Exogenous EPO also significantly diminished terminal deoxynucleotidyltransferase-mediated dUTP end labeling labeling of neurons in the ischemic retina, implying an antiapoptotic mechanism of action. These results further establish EPO as a neuroprotective agent in acute neuronal ischemic injury.
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PMID:Erythropoietin administration protects retinal neurons from acute ischemia-reperfusion injury. 1213 Jun 65

Erythropoietin (EPO) in the renal cortex is synthesized by fibroblast-like cells that are in direct contact with capillaries and adjacent tubular cells. Prompted by this anatomical relationship, we asked whether renal cells express EPO receptors (EPORs) through which EPO could act as a renotropic cytokine. We found that all regions of human, rat and mouse kidney, mesangial and proximal and distal tubular cells express authentic EPORs. Similar EPOR expression was detected in kidney cancer cells, and in cyst epithelia from polycystic kidneys. In vitro, EPO stimulated mitogenesis in all normal and malignant cells, and cell survival and motogenesis in injured tubular cells. Since the normal kidney is essentially unresponsive to EPO, we hypothesized that EPO's cytokine effects in the kidney are revealed when tubular cells are induced to proliferate by a prior insult, as occurs in acute renal failure. Accordingly, we found that EPO treatment of rats with 'ischemic' acute renal failure afforded renoprotection and accelerated functional recovery.
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PMID:Unexpected renal actions of erythropoietin. 1238 12

Erythropoietin (EPO), originally recognized for its central role in erythropoiesis, has been shown to improve neurological outcome after stroke. Here, we investigated the treatment of experimental autoimmune encephalomyelitis (EAE) in mice with EPO. Mice were treated with recombinant human EPO (rhEPO) upon onset of paresis. Neurological functional tests were scored daily by grading of clinical signs (score 0-5). Hematoxylin and eosin (HE) staining of cerebral tissue was performed to detect inflammatory infiltrates. Double staining for Luxol fast blue and Bielshowsky was used to demonstrate myelin and axons, respectively. Immunohistochemistry was performed to measure the expression of bromodeoxyuridine (BrdU, a marker for cell proliferation), NG2 (a marker for oligodendrocyte progenitor cells) and brain-derived neurotrophic factor (BDNF). Treatment with rhEPO significantly improved neurological functional recovery, reduced inflammatory infiltrates and demyelination, and increased oligodendrocyte progenitor cell proliferation and BDNF+ cells compared to the EAE controls. These data indicate that rhEPO treatment improved functional recovery after EAE in mice, possibly, via stimulating oligodendrogenesis, downregulating proinflammatory infiltrates and by elevating BDNF expression.
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PMID:Erythropoietin treatment improves neurological functional recovery in EAE mice. 1571 57

Erythropoietin (EPO), the principal hematopoietic cytokine produced by the kidney and the liver in fetuses, regulates mammalian erythropoiesis and exhibits diverse cellular effects in non-hematopoietic tissues. The introduction of recombinant human EPO (rhEPO) has marked a significant advance in the management of anemia associated with chronic renal failure. At the same time, experimental studies have unveiled its potential cardioprotective actions. As with other preconditioning agents, administration of exogenous rhEPO can confer myocardial protection against ischemia-reperfusion injury, in terms of reduction in cellular apoptosis and necrosis as well as improvement in myocardial functional recovery. The purpose of this study is to review current information regarding the various protocols used to investigate the effects of rhEPO administration as well as its cardioprotective properties. We also address the potential mechanisms underlying the protective effects of EPO. A better understanding of these mechanisms is essential for the development of clinical applications and the design of novel therapeutical strategies.
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PMID:Erythropoietin and myocardial protection: what's new? 1601 30

Erythropoietin (EPO), a pleiotropic cytokine involved in erythropoiesis, is tissue-protective in ischemic, traumatic, toxic and inflammatory injuries. In this study, we investigated the effect of EPO in experimental intracerebral hemorrhage (ICH). Two hours after inducing ICH via the stereotaxic infusion of collagenase, recombinant human EPO (500 or 5000 IU/kg, ICH + EPO group) or PBS (ICH + vehicle group) was administered intraperitoneally, then once daily afterwards for 1 or 3 days. ICH + EPO showed the better functional recovery in both rotarod and modified limb placing tests. The brain water content was decreased in ICH + EPO dose-dependently, as compared with ICH + vehicle. The effect of EPO on the brain water content was inhibited by N(omega)-Nitro-L-arginine methyl ester hydrochloride (L-NAME, 10 mg/kg). Mean hemorrhage volume was also decreased in ICH + EPO. EPO reduced the numbers of TUNEL +, myeloperoxidase + or OX-42 + cells in the perihematomal area. In addition, EPO reduced the mRNA level of TNF-alpha, Fas and Fas-L, as well as the activities of caspase-8, 9 and 3. EPO treatment showed up-regulations of endothelial nitric oxide synthase (eNOS) and p-eNOS, pAkt, pSTAT3 and pERK levels. These data suggests that EPO treatment in ICH induces better functional recovery with reducing perihematomal inflammation and apoptosis, coupled with activations of eNOS, STAT3 and ERK.
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PMID:Erythropoietin reduces perihematomal inflammation and cell death with eNOS and STAT3 activations in experimental intracerebral hemorrhage. 1653 88

Erythropoietin (EPO) has been used widely for the treatment of anaemia associated with chronic kidney disease and cancer chemotherapy for nearly 20 years. More recently, EPO has been found to interact with its receptor (EPO-R) expressed in a large variety of non-haematopoietic tissues to induce a range of cytoprotective cellular responses, including mitogenesis, angiogenesis, inhibition of apoptosis and promotion of vascular repair through mobilization of endothelial progenitor cells from the bone marrow. Administration of EPO or its analogue, darbepoetin, promotes impressive renoprotection in experimental ischaemic and toxic acute renal failure, as evidenced by suppressed tubular epithelial apoptosis, enhanced tubular epithelial proliferation and hastened functional recovery. This effect is still apparent when administration is delayed up to 6 h after the onset of injury and can be dissociated from its haematological effects. Based on these highly encouraging results, at least one large randomized controlled trial of EPO therapy in ischaemic acute renal failure is currently underway. Preliminary experimental and clinical evidence also indicates that EPO may be renoprotective in chronic kidney disease. The purpose of the present article is to review the renoprotective benefits of different protocols of EPO therapy in the settings of acute and chronic kidney failure and the potential mechanisms underpinning these renoprotective actions. Gaining further insight into the pleiotropic actions of EPO will hopefully eventuate in much-needed, novel therapeutic strategies for patients with kidney disease.
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PMID:Novel renoprotective actions of erythropoietin: new uses for an old hormone. 1688 70

The aim of the present study is to evaluate the effects of erythropoietin to the collateral sprouting by using systemically delivered erythropoietin in an end-to-side nerve repair model. Forty-five rats were evaluated in four groups: (A) end-to-side neurorrhaphy only, (B) end-to-side neurorrhaphy and erythropoietin administration, (C) end-to-end neurorrhaphy and (D) nerve stumps buried into neighboring muscles. In all animals, the contralateral healthy side served as control. Functional assessment of nerve regeneration was performed at intervals up to 5 months using the Peroneal Function Index. Evaluation 150 days after surgery included peroneal and tibial nerve morphometric examination, and wet weights of the tibialis anterior muscle. During the first three weeks after surgery, when erythropoietin was regularly administered, functional evaluation showed that erythropoietin may facilitate peripheral nerve regeneration. However, there was rapid deterioration in the functional recovery when erythropoietin's administration was discontinued. As a consequence, at the end of this study, erythropoietin failed to maintain its initial stimulating effect in axonal regeneration. The results of wet muscle weights revealed statistically significant differences between Groups A and C, and Group B. Furthermore, data on axonal counting showed significant difference between Groups A and C, and Group B. Erythropoietin appears to facilitate peripheral nerve regeneration at the initial phase of its administration. Further investigation will be necessary to optimise the conditions (dose, mode of administration) in order to maintain its effects.
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PMID:Axonal regeneration stimulated by erythropoietin: an experimental study in rats. 1753 73

Erythropoietin (EPO), the principal hematopoietic hormone produced by the kidney and the liver in fetuses, regulates mammalian erythropoiesis and exhibits diverse cellular effects in nonhematopoietic tissues. The introduction of recombinant human EPO (rhEPO) has marked a significant advance in the management of anemia associated with chronic renal failure. At the same time, experimental studies have unveiled its potential neuroprotective and cardioprotective properties, occurring independently of its hematopoietic action. As with other cytoprotective agents, administration of exogenous rhEPO can confer cerebral and myocardial protection against ischemia-reperfusion injury in terms of reduction in cellular apoptosis and necrosis, as well as improvement in functional recovery. Very recent studies even suggest that this drug could have beneficial applications in oncology, protecting against chemotherapy cardiotoxicity. The purpose of this letter is to review current information regarding the various conditions in which rhEPO and its derivates could confer cellular protection. We also address clinical perspectives and novel therapeutic strategies that could be developed based on these studies. Thus, EPO seems to be a very promising agent for protecting cellular survival during both acute and chronic diseases, and its future should be considered with enthusiasm.
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PMID:Cellular protection by erythropoietin: new therapeutic implications? 1771 90

Erythropoietin (Epo) has neuroprotective activity in a variety of settings. Thus, we investigated whether Epo has a role in the functional recovery of rats after facial nerve injury. The right facial nerve of 24 Wistar rats (6 wks old) was crushed twice at the level of the stylomastoid foramen, for 30 s each time, using jeweler's forceps held perpendicular to the nerve. The left facial nerve did not undergo the surgical lesion. The rats were randomly divided into 4 groups: (group 1) the control group (placebo, treated with saline); and groups treated with Epo at a dose of 1,000 U/kg body weight (group 2), 5,000 U/kg body weight (group 3), and 10,000 U/kg body weight (group 4). The Epo and saline were administered subcutaneously pre-operatively and treatment was repeated every 24 h for the first 2 weeks after the operation. Behavioral recovery from facial paralysis was measured daily, beginning 1 day after surgery, until full recovery of the eye blink reflex and whisker movements were observed. The average recovery times for the full blink reflex and whisker movements were significantly shorter (about 2-3 days) in rats treated with a high dose Epo (5,000, 10,000 U/kg body weight) compared to the placebo-treated rats (p<0.05). There was no significant difference between low dose Epo-treated rats (1,000 U/kg body weight) and the placebo-treated rats. These results suggest that high dose Epo can promote the functional recovery of rats following facial nerve injury. Further studies are warranted to probe alternative treatment schedules (dose, mode of administration), underlying histological mechanisms and combination treatment with additional neuroprotective factors.
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PMID:High dose erythropoietin promotes functional recovery of rats following facial nerve crush. 1923 Nov 94


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