Erythropoietin Protects from Post-Traumatic Edema in the Rat Brain

Verdonck, Olivier; Lahrech, Hana; Francony, Gilles; Carle, Olivier; Farion, Régine; Looij, Yohan van de; Rémy, Chantal; Segebarth, Christoph; Payen, Jean François

doi:10.1038/sj.jcbfm.9600443

Cited by 80 publications

(62 citation statements)

References 46 publications

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“…Such a model mimics several pathophysiological characteristics of human focal cortical contusion (Nag, 1996) and produces a reproducible, demarcated lesion to the neocortex that allows evaluation of the efficacy of compounds with a neuroprotective potential (Hortobagyi et al, 2000). The present findings extend previous work by showing that rHuEPO significantly reduces brain injury and improves neurological recovery following traumatic insults (Brines et al, 2000;Lu et al, 2005;Ozturk et al, 2005;Shein et al, 2005;Siren et al, 2006;Verdonck et al, 2007;Yatsiv et al, 2005). In particular, rHuEPO administration improved both functional and cognitive recovery of the rats with an effect that was significantly shown since the early stage after TBI and lasted for 15 days.…”

Section: Discussionsupporting

confidence: 79%

“…Although the role of EPO as a neuroprotectant has been studied extensively in a wide range of in vitro and in vivo models of brain injury, up to date, there are only few studies evaluating the effect of rHuEPO after experimental TBI (Brines et al, 2000;Lu et al, 2005;Ozturk et al, 2005;Shein et al, 2005;Siren et al, 2006;Verdonck et al, 2007;Yatsiv et al, 2005) and none has used a cryogenic injury paradigm. Neurobehavioral improvement after EPO administration has been reported in other studies where different models of brain injury were used.…”

Section: Discussionmentioning

confidence: 99%

“…In this scenario, a large body of evidence has pointed out the efficacy of the hormone erythropoietin (EPO) as neuroprotectant. Although peripherally administered recombinant human EPO (rHuEPO) has shown to penetrate the blood-brain barrier (BBB) and reduce brain injury following a variety of insults (Brines et al, 2000;Digicaylioglu and Lipton, 2001;Grasso et al, 2004), its potential neuroprotective efficacy in an in vivo model of experimental TBI has been scarcely investigated (Brines et al, 2000;Lu et al, 2005;Ozturk et al, 2005;Shein et al, 2005;Siren et al, 2006;Verdonck et al, 2007;Yatsiv et al, 2005). Evidence shows widespread efficacy of rHuEPO in injury models of spinal cord (Celik et al, 2002;Gorio et al, 2002;Grasso et al, 2006), subarachnoid hemorrhage (Buemi et al, 2002a,b;Catania et al, 2002;Grasso, 2001;Grasso et al, 2002a,b;Springborg et al, 2002), retina, and the heart damage (Calvillo et al, 2003;Junk et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Neuroprotection by erythropoietin administration after experimental traumatic brain injury

et al. 2007

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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 blood-brain barrier (BBB) breakdown was evaluated by assay of Evans blue extravasation. Furthermore, extent of cerebral damage was assessed. Administration of rHuEPO markedly improved recovery from motor dysfunction compared with placebo group (P < 0.05). Brain edema was significantly reduced in the cortex of the EPO-treated group relative to that in the placebo-treated group (80.6 ± 0.3% versus 91.8% ± 0.8% respectively, P < 0.05). BBB breakdown was significantly lower in EPO-treated group than in the placebo-treated group (66.2 ± 18.7 μg/g versus 181.3 ± 21 μg/g, respectively, P < 0.05). EPO treatment reduced injury volume significantly compared with placebo group (17.4 ± 5.4 mm3 versus 37.1 ± 5.3 mm3, P < 0.05). EPO, administered in its recombinant form, affords significant neuroprotection in experimental TBI model and may hold promise for future clinical applications.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Neuroprotection by erythropoietin administration after experimental traumatic brain injury

et al. 2007

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“…67,76 -86 Brain edema after experimental injury can effectively be attenuated by posttreatment with EPO. 76,78,83 Mechanisms which account for the beneficial actions after traumatic injuries include inhibition of apoptosis, anti-inflammatory and anti-oxidant actions, restoration of blood-brain barrier integrity, stimulation of neurogenesis, and angiogenesis, 7,8,67,76 -84 but it is not yet clear which of the neuroprotective effects of EPO are responsible for the long-term prevention of trauma-induced brain atrophy, cognitive and neurobehavioral dysfunction. 86 Recovery of both motor function and reduction of the histopathological damage by EPO and its nonerythropoietic derivatives CEPO and asialo-EPO have been reported in various, but not all, models of spinal cord injury.…”

Section: Traumatic Brain Injury and Spinal Cord Injurymentioning

confidence: 99%

Therapeutic Potential of Erythropoietin and its Structural or Functional Variants in the Nervous System

et al. 2009

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Summary:The growth factor erythropoietin (EPO) and erythropoietin receptors (EPOR) are expressed in the nervous system. Neuronal expression of EPO and EPOR peaks during brain development and is upregulated in the adult brain after injury. Peripherally administered EPO, and at least some of its variants, cross the blood-brain barrier, stimulate neurogenesis, neuronal differentiation, and activate brain neurotrophic, antiapoptotic, anti-oxidant and anti-inflammatory signaling. These mechanisms underlie their tissue protective effects in nervous system disorders. As the tissue protective functions of EPO can be separated from its stimulatory action on hematopoiesis, novel EPO derivatives and mimetics, such as asialo-EPO and carbamoylated EPO have been developed. While the therapeutic potential of the novel EPO derivatives continues to be characterized in preclinical studies, the experimental findings in support for the use of recombinant human (rh)EPO in human brain disease have already been translated to clinical studies in acute ischemic stroke, chronic schizophrenia, and chronic progressive multiple sclerosis. In this review article, we assess the studies on EPO and, in particular, on its structural or functional variants in experimental models of nervous system disorders, and we provide a short overview of the completed and ongoing clinical studies testing EPO as neuroprotective/neuroregenerative treatment option in neuropsychiatric disease.

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“…In addition, administration of EPO also represents a viable option for the prevention of retinal cell injury during glutamate toxicity [233] and glaucoma [234]. Systemic application of EPO also can improve functional outcome and reduce cell loss during spinal cord injury [235,236], traumatic cerebral edema [237], cortical trauma [238], and epileptic activity [211,239]. In direct relation to the potential protective cerebral effects of EPO, enhanced survival by EPO also extends to afford protection of the neurovascular unit during cerebral vascular disease [17,240].…”

Section: Erythropoietin a Cytokine And Growth Factormentioning

confidence: 99%

Triple play: Promoting neurovascular longevity with nicotinamide, WNT, and erythropoietin in diabetes mellitus

Maiese

2008

Biomedicine & Pharmacotherapy

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SummaryOxidative stress is a principal pathway for the dysfunction and ultimate destruction of cells in the neuronal and vascular systems for several disease entities, non promoting the ravages of oxidative stress to any less of a degree than diabetes mellitus. Diabetes mellitus is increasing in incidence as a result of changes in human behavior that relate to diet and daily exercise and is predicted to affect almost 400 million individuals worldwide in another two decades. Furthermore, both type 1 and type 2 diabetes mellitus can lead to significant disability in the nervous and cardiovascular systems, such as cognitive loss and cardiac insufficiency. As a result, innovative strategies that directly target oxidative stress to preserve neuronal and vascular longevity could offer viable therapeutic options to diabetic patients in addition to more conventional treatments that are designed to control serum glucose levels. Here we discuss the novel application of nicotinamide, Wnt signaling, and erythropoietin that modulate cellular oxidative stress and offer significant promise for the prevention of diabetic complications in the nervous and vascular systems. Essential to this process is the precise focus upon diverse as well as common cellular pathways governed by nicotinamide, Wnt signaling, and erythropoietin to outline not only the potential benefits, but also the challenges and possible detriments of these therapies. In this way, new avenues of investigation can hopefully bypass toxic complications, or at the very least, avoid contraindications that may limit care and offer both safe and robust clinical treatment for patients.

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Erythropoietin Protects from Post-Traumatic Edema in the Rat Brain

Cited by 80 publications

References 46 publications

Neuroprotection by erythropoietin administration after experimental traumatic brain injury

Neuroprotection by erythropoietin administration after experimental traumatic brain injury

Therapeutic Potential of Erythropoietin and its Structural or Functional Variants in the Nervous System

Triple play: Promoting neurovascular longevity with nicotinamide, WNT, and erythropoietin in diabetes mellitus

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