0000000000324473
AUTHOR
Michele Buemi
Down with the erythropoietin. Long live the erythropoietin!
In recent years the use of erythropoietin has exploded, and the anaemia of patients with chronic renal failure has been practically resolved with the administration of rHuEpo (recombinant human, Erythropoietin). However, as a result of an intense commercial campaign, strong therapies with this growth hormone, prescribed to achieve surprising sporting performances, got athletes to run the risk of thrombosis and vascular accidents because of red blood cells increase. Erythropoietin represents a significant subject of research. In fact, besides the ability of stimulating erythrocyte production, it has many pleiotropic effects. Several studies allow the assertion that EPO, in different concentr…
Erythropoietin and erythropoietin receptor expression after experimental spinal cord injury encourages therapy by exogenous erythropoietin
OBJECTIVE: Erythropoietin (EPO) is a pleiotropic cytokine originally identified for its role in erythropoiesis. Recent studies have demonstrated that EPO and its receptor (EPO-R) are expressed in the central nervous system, where EPO exerts neuroprotective functions. Because the expression of the EPO and EPO-R network is poorly investigated in the central nervous system, the aim of the present study was to investigate whether the resident EPO and EPO-R network is activated in the injured nervous system. METHODS: A well-standardized model of compressive spinal cord injury in rats was used. EPO and EPO-R expression was determined by immunohistochemical analysis at 8 hours and at 2, 8, and 14 …
Amelioration of spinal cord compressive injury by pharmacological preconditioning with erythropoietin and a nonerythropoietic erythropoietin derivative.
Object Spinal cord injury (SCI) is a devastating clinical syndrome for which no truly efficacious therapy has yet been identified. In preclinical studies, erythropoietin (EPO) and its nonerythropoietic derivatives asialoEPO and carbamylated EPO have markedly improved functional outcome when administered after compressive SCI. However, an optimum treatment paradigm is currently unknown. Because the uninjured spinal cord expresses a high density of EPO receptor (EPOR) in the basal state, signaling through these existing receptors in advance of injury (pharmacological preconditioning) might confer neuroprotection and therefore be potentially useful in situations of anticipated damage. Methods…
The Role of Erythropoietin in Aneurysmal Subarachnoid Haemorrhage: From Bench to Bedside
Subarachnoid haemorrhage (SAH) caused by a ruptured aneurysm accounts for only 5 % of strokes, but occurs at a fairly young age and carries a poor prognosis. Delayed cerebral ischaemia (DCI) is an important cause of death and dependence after aneurysmal SAH. The current mainstay of preventing DCI is nimodipine and maintenance of normovolemia, but even with this strategy DCI occurs in a considerable proportion of patients.
Erythropoietin in Traumatic Brain Injury: An Answer Will Come Soon
Traumatic brain injury (TBI) is a major cause of morbidity and mortality in the United States. It is estimated that each year TBIs are associated with 1.1 million emergency department visits, 235,000 hospitalizations, and 50,000 deaths (1). Despite improvements in medical interventions, there are still no neuroprotective agents available to counteract secondary or delayed damage to the traumatically injured human brain or to promote its repair. TBI encompasses heterogeneous etiologic, anatomical, and molecular patterns of injury that exhibit different propensities to cause cerebral damage. Without careful consideration of individual injuries, the results of therapeutic trials remain difficu…
Intravenous recombinant erythropoietin does not lead to an increase in cerebrospinal fluid erythropoietin concentration
No abstract
Neuroprotective potential of erythropoietin and darbepoetin alfa in an experimental model of sciatic nerve injury. Laboratory investigation.
Object The objectives of this study were to examine whether the systemic administration of recombinant human erythropoietin (rHuEPO) and its long-lasting derivative darbepoetin alfa expedited functional recovery in a rat model of sciatic nerve injury, and to compare the effects of these agents in the model. Methods Thirty male Sprague–Dawley rats received a crush injury to the left sciatic nerve and subsequently underwent either placebo treatment, daily injections of rHuEPO, or weekly injections of darbepoetin alfa. Results Both rHuEPO and darbepoetin alfa were effective in reducing neurological impairment and improving compound muscle action potentials following nerve injury. Darbepoetin …
Proteinuric effect of transcranial magnetic stimulation in healthy subjects and diabetic patients with stage 3-4 CKD
BackgroundMany authors have investigated the numerous connections between the nervous system and kidneys, and recent literature has indicated that these similar systems are interconnected. Recent scientific works have shown that there is similarity between the cerebral cortex 'viscera representation' and the 'motor omunculus'. We studied the connection between the brain and kidney in vivo using repetitive transcranial magnetic stimulation (rTMS). Proteinuria and albuminuria were used as markers of renal response in patients with diabetes (DP) and in a group of healthy subjects (HSs) who received rTMS for 5 consecutive days.MethodsThe study population consists of the following four groups: G…
Brain and Cancer: The Protective Role of Erythropoietin
Erythropoietin (Epo) is a pleiotropic agent, that is to say, it can act on several cell types in different ways. An independent system Epo/Epo receptor (EpoR) was detected in brain, leading to the hypothesis that this hormone could be involved in cerebral functions. Epo/EpoR expression changes during ontogenesis, thus indicating the importance of this system in neurodevelopment. Moreover, the hypoxia-induced production of Epo in the adult brain suggests that it could exert a neurotrophic and neuroprotective effect in case of brain injury. Epo could also influence neuro- transmission, inducing neurotransmitters (NT) release. Epo therapy in anemic cancer patients is still a controversial issu…
Regenerative Medicine: Does Erythropoietin have a Role?
Regenerative Medicine, a recent new medical domain, aims to develop new therapies through the stimulation of natural regenerative processes also in human beings. In this field, Erythropoietin (EPO) represents a significant subject of research. Several studies allow the assertion that EPO, in different concentrations, has protective effects mainly on the central nervous system, cardiovascular system and renal tissue. This action is carried out through one of few regenerative activities of human beings: angiogenesis. This mechanism, which involves endothelial stem cells and VEGF (Vascular Endothelial Growth Factor), has been experimentally demonstrated with Recombinant human erythropoietin (r…
Neuroprotection by erythropoietin administration after experimental traumatic brain injury.
A large body of evidence indicates that the hormone erythropoietin (EPO) exerts beneficial effects in the central nervous system (CNS). To date, EPO's effect has been assessed in several experimental models of brain and spinal cord injury. This study was conducted to validate whether treatment with recombinant human EPO (rHuEPO) would limit the extent of injury following experimental TBI. Experimental TBI was induced in rats by a cryogenic injury model. rHuEPO or placebo was injected intraperitoneally immediately after the injury and then every 8 h until 2 or 14 days. Forty-eight hours after injury brain water content, an indicator of brain edema, was measured with the wet-dry method and bl…
CKD NUTRITION, INFLAMMATION AND OXIDATIVE STRESS
Introduction and Aims: Serum p-cresyl sulfate associates with cardiovascular disease in patients at different stages of chronic kidney disease. p-Cresyl sulfate concentrations are determined by intestinal uptake of p-cresol, human metabolism to p-cresyl sulfate and renal clearance. Whether intestinal uptake of p-cresol itself is associated with cardiovascular disease in patients with renal disease has not been studied to date. Methods: We performed a prospective study in patients with chronic kidney disease stage 1-5 (clinicaltrials.gov NCT00441623). Intestinal uptake of p-cresol, under steady state conditions, was estimated from 24h urinary excretion of p-cresyl sulfate. Primary endpoint w…
Neuroprotective effect of erythropoietin and darbepoetin alfa after experimental intracerebral hemorrhage.
OBJECTIVE: Intracerebral hemorrhage (ICH) is a devastating clinical syndrome for which no truly efficacious therapy has yet been identified. In preclinical studies, erythropoietin (EPO) and its long-lasting analog, darbepoetin alfa, have been demonstrated to be neuroprotective in several models of neuronal insult. The objectives of this study were to analyze whether the systemic administration of recombinant human EPO (rHuEPO) and its long-lasting derivative darbepoetin alfa expedited functional recovery and brain damage in a rat model of ICH. METHODS: Experimental ICH was induced in rats by injecting autologous blood into the right striatum under stereotactic guidance. Subsequently, animal…
The erythropoietin and regenerative medicine: a lesson from fish
Background Erythropoietin (EPO), the main haematopoietic growth factor for the proliferation and differentiation of erythroid progenitor cells, is also known for its angiogenic and regenerative properties. Materials and methods In this study, we aimed to test the regenerative effects of EPO administration in an experimental model of Sea bass (Dicentrarchus labrax) subjected to amputation of the caudal fin. Results Erythropoietin-treated fishes (3000 UI of human recombinant EPO-alpha immediately after cutting and after 15 days) showed an increased growth rate of their fins compared with those untreated (ANOVA variance: P :0 AE01 vs. P :0 AE04). By analysing fin length at established times (1…