Erythropoietin attenuates motor impairments induced by bilateral renal ischemia/reperfusion in rats

Tahamtan, Mahshid; Moosavi, Seyed Mostafa Shid; Sheibani,; Nayebpour, Mohsen; Esmaeili‐Mahani, Saeed; Shabani, Mohammad

doi:10.1111/fcp.12226

Cited by 14 publications

(10 citation statements)

References 31 publications

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“…Concerning muscle function, bilateral IRI induced by an hour occlusion confers poor motor coordination and balance in the rotarod experiment after one week, while grip strength was not altered [ 110 ]. Deterioration in the rotarod test indicates a deficit in motor coordination or fatigue resistance, so this could be worth investigating, as behavioral deficits occur even with mild renal failure, which may be due to uremic encephalopathy rather than uremic sarcopenia [ 136 ].…”

Section: Experimental Laboratory Tools For Exploration Of Uremic Smentioning

confidence: 99%

“…Indeed, the presence and bioactivity of the receptor in non-hematopoietic tissues implies that EPO exerts a pleiotropic effect in various tissues and organs [ 169 , 170 ]. Intriguingly, endurance time as assessed with a rotarod test in bilateral IRI mice was improved with EPO (1000 U/kg) intraperitoneally injected 30 min prior to surgery [ 110 ]. Additionally, prolyl hydroxylase domain (HIF-PH) inhibitors, which are expected to be erythropoiesis-stimulating agents, are a new class of compounds that focus on enhancing endogenous EPO production [ 171 ].…”

Section: Exploration Of Interventions To Overcome Uremic Sarcopenimentioning

confidence: 99%

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Uremic Sarcopenia: Clinical Evidence and Basic Experimental Approach

et al. 2020

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Sustained physical activity extends healthy life years while a lower activity due to sarcopenia can reduce them. Sarcopenia is defined as a decrease in skeletal muscle mass and strength due not only to aging, but also from a variety of debilitating chronic illnesses such as cancer and heart failure. Patients with chronic kidney disease (CKD), who tend to be cachexic and in frail health, may develop uremic sarcopenia or uremic myopathy due to an imbalance between muscle protein synthesis and catabolism. Here, we review clinical evidence indicating reduced physical activity as renal function deteriorates and explore evidence-supported therapeutic options focusing on nutrition and physical training. In addition, although sarcopenia is a clinical concept and difficult to recapitulate in basic research, several in vivo approaches have been attempted, such as rodent subtotal nephrectomy representing both renal dysfunction and muscle weakness. This review highlights molecular mechanisms and promising interventions for uremic sarcopenia that were revealed through basic research. Extensive study is still needed to cast light on the many aspects of locomotive organ impairments in CKD and explore the ways that diet and exercise therapies can improve both outcomes and quality of life at every level.

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Section: Experimental Laboratory Tools For Exploration Of Uremic Smentioning

confidence: 99%

Section: Exploration Of Interventions To Overcome Uremic Sarcopenimentioning

confidence: 99%

Uremic Sarcopenia: Clinical Evidence and Basic Experimental Approach

et al. 2020

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“…Reduction of locomotor activity is another symptom of hippocampal cytotoxicity that has been shown 24 hours and 1 week after renal reperfusion of bilateral ischemia [50]. It seems that destruction of CA1 neurons following AKI is involved in animals’ hypo-activity [20].…”

Section: Hippocampus Cytotoxicity and Apoptosismentioning

confidence: 99%

Brain consequences of acute kidney injury: Focusing on the hippocampus

Malek

2018

Kidney Res Clin Pract.

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The high mortality rates associated with acute kidney injury are mainly due to extra-renal complications that occur following distant-organ involvement. Damage to these organs, which is commonly referred to as multiple organ dysfunction syndrome, has more severe and persistent effects. The brain and its sub-structures, such as the hippocampus, are vulnerable organs that can be adversely affected. Acute kidney injury may be associated with numerous brain and hippocampal complications, as it may alter the permeability of the blood-brain barrier. Although the pathogenesis of acute uremic encephalopathy is poorly understood, some of the underlying mechanisms that may contribute to hippocampal involvement include the release of multiple inflammatory mediators that coincide with hippocampus inflammation and cytotoxicity, neurotransmitter derangement, transcriptional dysregulation, and changes in the expression of apoptotic genes. Impairment of brain function, especially of a structure that has vital activity in learning and memory and is very sensitive to renal ischemic injury, can ultimately lead to cognitive and functional complications in patients with acute kidney injury. The objective of this review was to assess these complications in the brain following acute kidney injury, with a focus on the hippocampus as a critical region for learning and memory.

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“…EPO acts on its receptor (EPOR) to activate different kinases and intracellular signaling pathways in various nonhematopoietic tissues, such as in the kidney, endothelial cells, central nervous system (CNS), heart, and reproductive tract [ 22 – 26 ]. EPO has been used to protect against neurotoxicity [ 21 ], ischemia/reperfusion injury [ 27 , 28 ], and neurologic diseases [ 29 , 30 ]. n in vitro or vivo models, EPO has been effective in improving functional outcomes after the experimental induction of traumatic brain injury [ 31 – 33 ] and spinal cord injury [ 34 ], limiting neuronal damage-associated epilepsy [ 35 , 36 ] and reducing chemotherapy-induced peripheral neurotoxicity [ 37 , 38 ].…”

Section: Introductionmentioning

confidence: 99%

Erythropoietin attenuates motor neuron programmed cell death in a burn animal model

Lee

et al. 2018

PLoS ONE

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Burn-induced neuromuscular dysfunction may contribute to long-term morbidity; therefore, it is imperative to develop novel treatments. The present study investigated whether erythropoietin (EPO) administration attenuates burn-induced motor neuron apoptosis and neuroinflammatory response. To validate our hypothesis, a third-degree hind paw burn rat model was developed by bringing the paw into contact with a metal surface at 75°C for 10 s. A total of 24 male Sprague–Dawley rats were randomly assigned to four groups: Group A, sham-control; Group B, burn-induced; Group C, burn + single EPO dose (5000 IU/kg i.p. at D0); and Group D, burn + daily EPO dosage (3000 IU/kg/day i.p. at D0–D6). Two treatment regimens were used to evaluate single versus multiple doses treatment effects. Before sacrifice, blood samples were collected for hematological parameter examination. The histological analyses of microglia activation, iNOS, and COX-2 in the spinal cord ventral horn were performed at week 1 post-burn. In addition, we examined autophagy changes by biomarkers of LC3B and ATG5. The expression of BCL-2, BAX, cleaved caspase-3, phospho-AKT, and mTOR was assessed simultaneously through Western blotting. EPO administration after burn injury attenuated neuroinflammation through various mechanisms, including the reduction of microglia activity as well as iNOS and COX-2 expression in the spinal cord ventral horn. In addition, the expression of phospho-AKT, mTOR and apoptotic indicators, such as BAX, BCL-2, and cleaved caspase-3, was modulated. Furthermore, the activity of burn-induced autophagy in the spinal cord ventral horn characterized by the expression of autophagic biomarkers, LC3B and ATG5, was reduced after EPO administration. The present results indicate that EPO inhibits the AKT-mTOR pathway to attenuate burn-induced motor neuron programmed cell death and microglia activation. EPO can modulate neuroinflammation and programmed cell death and may be a therapeutic candidate for neuroprotection.

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Erythropoietin attenuates motor impairments induced by bilateral renal ischemia/reperfusion in rats

Cited by 14 publications

References 31 publications

Uremic Sarcopenia: Clinical Evidence and Basic Experimental Approach

Uremic Sarcopenia: Clinical Evidence and Basic Experimental Approach

Brain consequences of acute kidney injury: Focusing on the hippocampus

Erythropoietin attenuates motor neuron programmed cell death in a burn animal model

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