Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Mini-Review Article

EPO and EPO-Receptor System as Potential Actionable Mechanism for the Protection of Brain and Heart in Refractory Epilepsy and SUDEP

Author(s): Jerónimo Auzmendi , María B. Puchulu, Julio C. G. Rodríguez , Ana M. Balaszczuk , Alberto Lazarowski and Amalia Merelli *

Volume 26, Issue 12, 2020

Page: [1356 - 1364] Pages: 9

DOI: 10.2174/1381612826666200219095548

Price: $65

Abstract

The most important activity of erythropoietin (EPO) is the regulation of erythrocyte production by activation of the erythropoietin receptor (EPO-R), which triggers the activation of anti-apoptotic and proliferative responses of erythroid progenitor cells. Additionally, to erythropoietic EPO activity, an antiapoptotic effect has been described in a wide spectrum of tissues. EPO low levels are found in the central nervous system (CNS), while EPO-R is expressed in most CNS cell types. In spite of EPO-R high levels expressed during the hypoxicischemic brain, insufficient production of endogenous cerebral EPO could be the cause of determined circuit alterations that lead to the loss of specific neuronal populations. In the heart, high EPO-R expression in cardiac progenitor cells appears to contribute to myocardial regeneration under EPO stimulation. Several lines of evidence have linked EPO to an antiapoptotic role in CNS and in heart tissue. In this review, an antiapoptotic role of EPO/EPO-R system in both brain and heart under hypoxic conditions, such as epilepsy and sudden death (SUDEP) has been resumed. Additionally, their protective effects could be a new field of research and a novel therapeutic strategy for the early treatment of these conditions and avoid SUDEP.

Keywords: Epilepsy, erythropoietin, erythropoietin receptor, P-glycoprotein, SUDEP, neuroprotection, cardioprotection.

« Previous Next »
[1]
Zhang Y, Wang L, Dey S, et al. Erythropoietin action in stress response, tissue maintenance and metabolism. Int J Mol Sci 2014; 15(6): 10296-333.
[http://dx.doi.org/10.3390/ijms150610296] [PMID: 24918289]
[2]
Bunn HF. Erythropoietin. Cold Spring Harb Perspect Med 2013; 3(3) a011619
[http://dx.doi.org/10.1101/cshperspect.a011619] [PMID: 23457296]
[3]
Ogunshola OO, Bogdanova AY. Epo and non-hematopoietic cells: what do we know? Methods Mol Biol 2013; 982: 13-41.
[http://dx.doi.org/10.1007/978-1-62703-308-4_2] [PMID: 23456860]
[4]
Semenza GL, Wang GL. A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. Mol Cell Biol 1992; 12(12): 5447-54.
[http://dx.doi.org/10.1128/MCB.12.12.5447] [PMID: 1448077]
[5]
Riksen NP, Hausenloy DJ, Yellon DM. Erythropoietin: ready for prime-time cardioprotection. Trends Pharmacol Sci 2008; 29(5): 258-67.
[http://dx.doi.org/10.1016/j.tips.2008.02.002] [PMID: 18359096]
[6]
Arcasoy MO. Non-erythroid effects of erythropoietin. Haematologica 2010; 95(11): 1803-5.
[http://dx.doi.org/10.3324/haematol.2010.030213] [PMID: 21037325]
[7]
Merelli A, Caltana L, Lazarowski A, Brusco A. Experimental evidence of the potential use of erythropoietin by intranasal administration as a neuroprotective agent in cerebral hypoxia. Drug Metabol Drug Interact 2011; 26(2): 65-9.
[http://dx.doi.org/10.1515/dmdi.2011.007] [PMID: 21756166]
[8]
Li GQ, Chen M. Cardioprotective effect of erythropoietin in rats with acute myocardial infarction through JNK pathway. Eur Rev Med Pharmacol Sci 2019; 23(3)(Suppl.): 153-60.
[PMID: 31389586]
[9]
Duggan M, Torkzaban B, Ahooyi TM, et al. Age-related neurodegenerative diseases. J Cell Physiol 2019. (Epub ahead of print)
[http://dx.doi.org/10.1002/jcp.29248] [PMID: 31556109]
[10]
Rama R, Garzón F, Rodríguez-Cruz Y, Maurice T, García-Rodríguez JC. Neuroprotective effect of Neuro-EPO in neurodegenerative diseases: “Alea jacta est”. Neural Regen Res 2019; 14(9): 1519-21.
[http://dx.doi.org/10.4103/1673-5374.255968] [PMID: 31089047]
[11]
Rodríguez Cruz Y, Strehaiano M, Rodríguez Obaya T, García Rodríguez JC, Maurice T. An intranasal formulation of erythropoietin (neuro-epo) prevents memory deficits and amyloid toxicity in the appswe transgenic mouse model of Alzheimer’s disease. J Alzheimers Dis 2017; 55(1): 231-48.
[http://dx.doi.org/10.3233/JAD-160500] [PMID: 27662300]
[12]
Merelli A, Czornyj L, Lazarowski A. Erythropoietin as a new therapeutic opportunity in brain inflammation and neurodegenerative diseases. Int J Neurosci 2015; 125(11): 793-7.
[http://dx.doi.org/10.3109/00207454.2014.989321] [PMID: 25405533]
[13]
Merelli A, Rodríguez JCG, Folch J, Regueiro MR, Camins A, Lazarowski A. Understanding the role of hypoxia inducible factor during neurodegeneration for new therapeutics opportunities. Curr Neuropharmacol 2018; 16(10): 1484-98.
[http://dx.doi.org/10.2174/1570159X16666180110130253] [PMID: 29318974]
[14]
Freeman RS, Barone MC. Targeting hypoxia-inducible factor (HIF) as a therapeutic strategy for CNS disorders. Curr Drug Targets CNS Neurol Disord 2005; 4(1): 85-92.
[http://dx.doi.org/10.2174/1568007053005154] [PMID: 15723616]
[15]
Sharp FR, Bernaudin M. HIF1 and oxygen sensing in the brain. Nat Rev Neurosci 2004; 5(6): 437-48.
[http://dx.doi.org/10.1038/nrn1408] [PMID: 15152194]
[16]
Piret JP, Mottet D, Raes M, Michiels C. Is HIF-1alpha a pro- or an anti-apoptotic protein? Biochem Pharmacol 2002; 64(5-6): 889-92.
[17]
Semenza GL. Regulation of oxygen homeostasis by hypoxia-inducible factor 1. Physiology (Bethesda) 2009; 24(2): 97-106.
[http://dx.doi.org/10.1152/physiol.00045.2008] [PMID: 19364912]
[18]
Genc S, Koroglu TF, Genc K. Erythropoietin and the nervous system Brain Res 2004. 1000, 1–2: 19-31.
[19]
Brines M, Cerami A. Emerging biological roles for erythropoietin in the nervous systemNATURE REVIEWS | NEUROSCIENCE 2005. 6: 485-94.
[20]
Ehrenreich H, Hasselblatt M, Dembowski C, et al. Erythropoietin therapy for acute stroke is both safe and beneficial. Mol Med 2002; 8(8): 495-505.
[http://dx.doi.org/10.1007/BF03402029] [PMID: 12435860]
[21]
Wei S, Luo C, Yu S, et al. Erythropoietin ameliorates early brain injury after subarachnoid haemorrhage by modulating microglia polarization via the EPOR/JAK2-STAT3 pathway. Exp Cell Res 2017. 15;361(2): 342352.
[22]
Merelli A, Caltana L, Girimonti P, Ramos AJ, Lazarowski A, Brusco A. Recovery of motor spontaneous activity after intranasal delivery of human recombinant erythropoietin in a focal brain hypoxia model induced by CoCl2 in rats. Neurotox Res 2011; 20(2): 182-92.
[http://dx.doi.org/10.1007/s12640-010-9233-8] [PMID: 21116766]
[23]
Kopcho N, Chang G, Komives EA. Dynamics of ABC transporter P-glycoprotein in three conformational states. Sci Rep 2019; 91:: 15092.
[24]
Merelli A, Ramos AJ, Lazarowski A, Auzmendi J. Convulsive Stress mimics brain hypoxia and promotes the p-glycoprotein (p-gp) and erythropoietin receptor overexpression. recombinant human erythropoietin effect on p-gp activity. Front Neurosci 2019; 13: 750.
[http://dx.doi.org/10.3389/fnins.2019.00750] [PMID: 31379495]
[25]
Bateman LM, Li CS, Seyal M. Ictal hypoxemia in localization-related epilepsy: analysis of incidence, severity and risk factors. Brain 2008; 131(Pt 12): 3239-45.
[http://dx.doi.org/10.1093/brain/awn277] [PMID: 18952672]
[26]
Moseley BD, Nickels K, Britton J, Wirrell E. How common is ictal hypoxemia and bradycardia in children with partial complex and generalized convulsive seizures? Epilepsia 2010; 51(7): 1219-24.
[http://dx.doi.org/10.1111/j.1528-1167.2009.02490.x] [PMID: 20067502]
[27]
Sözmen ŞÇ, Kurul SH, Yiş U, Tuğyan K, Baykara B, Yılmaz O. Neuroprotective effects of recombinant human erythropoietin in the developing brain of rat after lithium-pilocarpine induced status epilepticus. Brain Dev 2012; 34(3): 189-95.
[http://dx.doi.org/10.1016/j.braindev.2011.05.002] [PMID: 21600713]
[28]
Rey F, Balsari A, Giallongo T, et al. Erythropoietin as a neuroprotective molecule: an overview of its therapeutic potential in neurodegenerative diseases. ASN Neuro 2019; 11 1759091419871420
[http://dx.doi.org/10.1177/1759091419871420] [PMID: 31450955]
[29]
Li Q, Han Y, Du J, et al. Recombinant human erythropoietin protects against brain injury through blunting the mTORC1 pathway in the developing brains of rats with seizures. Life Sci 2018; 194: 15-25.
[http://dx.doi.org/10.1016/j.lfs.2017.12.014] [PMID: 29233655]
[30]
Mansoor SR, Hashemian M, Khalili-Fomeshi M, Ashrafpour M, Moghadamnia AA, Ghasemi-Kasman M. Upregulation of klotho and erythropoietin contributes to the neuroprotection induced by curcumin-loaded nanoparticles in experimental model of chronic epilepsy. Brain Res Bull 2018; 142: 281-8.
[http://dx.doi.org/10.1016/j.brainresbull.2018.08.010] [PMID: 30130550]
[31]
Bahçekapılı N, Akgün-Dar K, Albeniz I, et al. Erythropoietin pretreatment suppresses seizures and prevents the increase in inflammatory mediators during pentylenetetrazole-induced generalized seizures. Int J Neurosci 2014; 124(10): 762-70.
[http://dx.doi.org/10.3109/00207454.2013.878935] [PMID: 24397543]
[32]
Jantzie LL, Getsy PM, Firl DJ, Wilson CG, Miller RH, Robinson S. Erythropoietin attenuates loss of potassium chloride co-transporters following prenatal brain injury. Mol Cell Neurosci 2014; 61: 152-62.
[http://dx.doi.org/10.1016/j.mcn.2014.06.009] [PMID: 24983520]
[33]
Zheng H, Wang X, Tang Z, Zheng W, Li Z. The PI3K/Akt and ERK1/2 signaling pathways mediate the erythropoietin-modulated calcium influx in kainic acid-induced epilepsy. Neuroreport 2013; 24(6): 335-41.
[http://dx.doi.org/10.1097/WNR.0b013e32835ffe03] [PMID: 23518641]
[34]
Zellinger C, Seeger N, Hadamitzky M, et al. Impact of the erythropoietin-derived peptide mimetic Epotris on the histopathological consequences of status epilepticus. Epilepsy Res 2011; 96(3): 241-9.
[http://dx.doi.org/10.1016/j.eplepsyres.2011.06.009] [PMID: 21741213]
[35]
Jung KH, Chu K, Lee ST, et al. Molecular alterations underlying epileptogenesis after prolonged febrile seizure and modulation by erythropoietin. Epilepsia 2011; 52(3): 541-50.
[http://dx.doi.org/10.1111/j.1528-1167.2010.02916.x] [PMID: 21269282]
[36]
Jing M, Shingo T, Yasuhara T, et al. The combined therapy of intrahippocampal transplantation of adult neural stem cells and intraventricular erythropoietin-infusion ameliorates spontaneous recurrent seizures by suppression of abnormal mossy fiber sprouting. Brain Res 2009; 1295: 203-17.
[http://dx.doi.org/10.1016/j.brainres.2009.07.079] [PMID: 19646969]
[37]
Castaneda-Arellano R, Beas-Zarate C, Feria-Velasco AI, Bitar-Alatorre EW, Rivera-Cervantes MC. From neurogenesis to neuroprotection in the epilepsy: signalling by erythropoietin. Front Biosci 2014; 19: 1445-55.
[http://dx.doi.org/10.2741/4295] [PMID: 24896364]
[38]
Ma BX, Li J, Li H, Wu SS. Recombinant human erythropoietin protects myocardial cells from apoptosis via the janus-activated kinase 2/signal transducer and activator of transcription 5 pathway in rats with epilepsy. Curr Ther Res Clin Exp 2015; 77: 90-8.
[http://dx.doi.org/10.1016/j.curtheres.2015.07.001] [PMID: 26649078]
[39]
Jiang C, Xu Q, Xu K, et al. Effects of erythropoietin on STAT1 and STAT3 levels following cerebral ischemia-reperfusion in rats. Int J Neurosci 2013; 123(10): 684-90.
[http://dx.doi.org/10.3109/00207454.2013.817409] [PMID: 23786492]
[40]
Pellegrini L, Bennis Y, Guillet B, et al. Therapeutic benefit of a combined strategy using erythropoietin and endothelial progenitor cells after transient focal cerebral ischemia in rats. Neurol Res 2013; 35(9): 937-47.
[http://dx.doi.org/10.1179/1743132813Y.0000000235] [PMID: 23816235]
[41]
Yu Z, Tang L, Chen L, Li J, Wu W, Hu C. Erythropoietin reduces brain injury after intracerebral hemorrhagic stroke in rats. Mol Med Rep 2013; 8(5): 1315-22.
[http://dx.doi.org/10.3892/mmr.2013.1666] [PMID: 24008820]
[42]
Meng H, Guo J, Wang H, Yan P, Niu X, Zhang J. Erythropoietin activates Keap1-Nrf2/ARE pathway in rat brain after ischemia. Int J Neurosci 2014; 124(5): 362-8.
[http://dx.doi.org/10.3109/00207454.2013.848439] [PMID: 24063261]
[43]
Teoh J, Boulos S, Chieng J, Knuckey NW, Meloni BP. Erythropoietin increases neuronal NDPKA expression, and NDPKA up-regulation as well as exogenous application protects cortical neurons from in vitro ischemia-related insults. Cell Mol Neurobiol 2014; 34(3): 379-92.
[http://dx.doi.org/10.1007/s10571-013-0023-8] [PMID: 24395206]
[44]
Ratilal BO, Arroja MM, Rocha JP, et al. Neuroprotective effects of erythropoietin pretreatment in a rodent model of transient middle cerebral artery occlusion. J Neurosurg 2014; 121(1): 55-62.
[http://dx.doi.org/10.3171/2014.2.JNS132197] [PMID: 24702327]
[45]
Prosvirnina MS, Shmonin AA, Mel’nikova EV, Vlasov TD. Neuroprotective effects of erythropoietin in focal brain ischemia in rats. Bull Exp Biol Med 2014; 156(5): 642-4.
[http://dx.doi.org/10.1007/s10517-014-2415-2] [PMID: 24770748]
[46]
Romanova GA, Shakova FM, Barskov IV, et al. Neuroprotective and antiamnesic effect of erythropoietin derivatives after experimental ischemic injury of cerebral cortex. Bull Exp Biol Med 2015; 158(3): 318-21.
[http://dx.doi.org/10.1007/s10517-015-2751-x] [PMID: 25573359]
[47]
Yuen CM, Yeh KH, Wallace CG, et al. EPO-cyclosporine combination therapy reduced brain infarct area in rat after acute ischemic stroke: role of innate immune-inflammatory response, micro-RNAs and MAPK family signaling pathway. Am J Transl Res 2017; 9(4): 1651-66.
[PMID: 28469772]
[48]
Mršić-Pelčić J, Pilipović K, Pelčić G, Vitezić D, Župan G. Decrease in oxidative stress parameters after post-ischaemic recombinant human erythropoietin administration in the hippocampus of rats exposed to focal cerebral ischaemia. Basic Clin Pharmacol Toxicol 2017; 121(6): 453-64.
[http://dx.doi.org/10.1111/bcpt.12833] [PMID: 28639431]
[49]
Yoo SJ, Cho B, Lee D, et al. The erythropoietin-derived peptide MK-X and erythropoietin have neuroprotective effects against ischemic brain damage. Cell Death Dis 2017; 8(8)e3003-3
[http://dx.doi.org/10.1038/cddis.2017.381] [PMID: 28817120]
[50]
Mazur M, Miller RH, Robinson S. Postnatal erythropoietin treatment mitigates neural cell loss after systemic prenatal hypoxic-ischemic injury. J Neurosurg Pediatr 2010; 6(3): 206-21.
[http://dx.doi.org/10.3171/2010.5.PEDS1032] [PMID: 20809703]
[51]
Jantzie LL, Corbett CJ, Firl DJ, Robinson S. Postnatal erythropoietin mitigates impaired cerebral cortical development following subplate loss from prenatal hypoxia-ischemia. Cereb Cortex 2015; 25(9): 2683-95.
[http://dx.doi.org/10.1093/cercor/bhu066] [PMID: 24722771]
[52]
Zhang L, Wang L, Ning FB, Wang T, Liang YC, Liu YL. Erythropoietin reduces hippocampus injury in neonatal rats with hypoxic ischemic brain damage via targeting matrix metalloprotein-2. Eur Rev Med Pharmacol Sci 2017; 21(19): 4327-33.
[PMID: 29077163]
[53]
Ma S, Chen J, Chen C, et al. Erythropoietin rescues memory impairment in a rat model of chronic cerebral hypoperfusion via the EPO-R/JAK2/STAT5/PI3K/Akt/GSK-3β pathway. Mol Neurobiol 2018; 55(4): 3290-9.
[http://dx.doi.org/10.1007/s12035-017-0568-5] [PMID: 28488208]
[54]
Zhao H, Wang R, Wu X, et al. Erythropoietin delivered via intra-arterial infusion reduces endoplasmic reticulum stress in brain microvessels of rats following cerebral ischemia and reperfusion. J Neuroimmune Pharmacol 2015; 10(1): 153-61.
[http://dx.doi.org/10.1007/s11481-014-9571-z] [PMID: 25626440]
[55]
Souvenir R, Flores JJ, Ostrowski RP, Manaenko A, Duris K, Tang J. Erythropoietin inhibits HIF-1α expression via upregulation of PHD-2 transcription and translation in an in vitro model of hypoxia-ischemia. Transl Stroke Res 2014; 5(1): 118-27.
[http://dx.doi.org/10.1007/s12975-013-0312-z] [PMID: 24323731]
[56]
Simon F, Floros N, Ibing W, Schelzig H, Knapsis A. Neurotherapeutic potential of erythropoietin after ischemic injury of the central nervous system. Neural Regen Res 2019; 14(8): 1309-12.
[http://dx.doi.org/10.4103/1673-5374.253507] [PMID: 30964047]
[57]
Zhang SJ, Wang RL, Zhao HP, et al. MEPO promotes neurogenesis and angiogenesis but suppresses gliogenesis in mice with acute ischemic stroke. Eur J Pharmacol 2019; 849(849): 1-10.
[http://dx.doi.org/10.1016/j.ejphar.2019.01.066] [PMID: 30716313]
[58]
Sola A, Rogido M, Lee BH, Genetta T, Wen TC. Erythropoietin after focal cerebral ischemia activates the Janus kinase-signal transducer and activator of transcription signaling pathway and improves brain injury in postnatal day 7 rats. Pediatr Res 2005; 57(4): 481-7.
[http://dx.doi.org/10.1203/01.PDR.0000155760.88664.06] [PMID: 15718373]
[59]
Wang R, Zhao H, Li J, et al. Erythropoietin attenuates axonal injury after middle cerebral artery occlusion in mice. Neurol Res 2017; 39(6): 545-51.
[http://dx.doi.org/10.1080/01616412.2017.1316904] [PMID: 28413924]
[60]
Elliot-Portal E, Laouafa S, Arias-Reyes C, Janes TA, Joseph V, Soliz J. Brain-derived erythropoietin protects from intermittent hypoxia-induced cardiorespiratory dysfunction and oxidative stress in mice. Sleep (Basel) 2018; 41(7): 1-13.
[http://dx.doi.org/10.1093/sleep/zsy072] [PMID: 29697839]
[61]
Al-Sarraf H, Malatiali S, Al-Awadi M, Redzic Z. Effects of erythropoietin on astrocytes and brain endothelial cells in primary culture during anoxia depend on simultaneous signaling by other cytokines and on duration of anoxia. Neurochem Int 2018; 113: 34-45.
[http://dx.doi.org/10.1016/j.neuint.2017.11.014] [PMID: 29180303]
[62]
Wang R, Li J, Duan Y, Tao Z, Zhao H, Luo Y. Effects of erythropoietin on gliogenesis during cerebral ischemic/reperfusion recovery in adult mice. Aging Dis 2017; 8(4): 410-9.
[http://dx.doi.org/10.14336/AD.2016.1209] [PMID: 28840056]
[63]
Hassouna I, Ott C, Wüstefeld L, et al. Revisiting adult neurogenesis and the role of erythropoietin for neuronal and oligodendroglial differentiation in the hippocampus. Mol Psychiatry 2016; 21(12): 1752-67.
[http://dx.doi.org/10.1038/mp.2015.212] [PMID: 26809838]
[64]
Garrigue P, Hache G, Bennis Y, et al. Erythropoietin pretreatment of transplanted endothelial colony-forming cells enhances recovery in a cerebral ischemia model by increasing their homing ability: a SPECT/CT study. J Nucl Med 2016; 57(11): 1798-804.
[http://dx.doi.org/10.2967/jnumed.115.170308] [PMID: 27609786]
[65]
Launay T, Hagström L, Lottin-Divoux S, et al. Blunting effect of hypoxia on the proliferation and differentiation of human primary and rat L6 myoblasts is not counteracted by Epo. Cell Prolif 2010; 43(1): 1-8.
[http://dx.doi.org/10.1111/j.1365-2184.2009.00648.x] [PMID: 20070732]
[66]
Brines M, Cerami A. Erythropoietin-mediated tissue protection: reducing collateral damage from the primary injury response. J Intern Med 2008; 264(5): 405-32.
[http://dx.doi.org/10.1111/j.1365-2796.2008.02024.x] [PMID: 19017170]
[67]
Collino M, Thiemermann C, Cerami A, Brines M. Flipping the molecular switch for innate protection and repair of tissues: Long-lasting effects of a non-erythropoietic small peptide engineered from erythropoietin. Pharmacol Ther 2015; 151: 32-40.
[http://dx.doi.org/10.1016/j.pharmthera.2015.02.005] [PMID: 25728128]
[68]
Guven Bagla A, Ercan E, Asgun HF, et al. Experimental acute myocardial infarction in rats: HIF-1α, caspase-3, erythropoietin and erythropoietin receptor expression and the cardioprotective effects of two different erythropoietin doses. Acta Histochem 2013; 115(7): 658-68.
[http://dx.doi.org/10.1016/j.acthis.2013.01.005] [PMID: 23453036]
[69]
Lu J, Yao YY, Dai QM, et al. Erythropoietin attenuates cardiac dysfunction by increasing myocardial angiogenesis and inhibiting interstitial fibrosis in diabetic rats. Cardiovasc Diabetol 2012; 11: 105.
[http://dx.doi.org/10.1186/1475-2840-11-105] [PMID: 22954171]
[70]
Tramontano AF, Muniyappa R, Black AD, et al. Erythropoietin protects cardiac myocytes from hypoxia-induced apoptosis through an Akt-dependent pathway. Biochem Biophys Res Commun 2003; 308(4): 990-4.
[http://dx.doi.org/10.1016/S0006-291X(03)01503-1] [PMID: 12927817]
[71]
Wright GL, Hanlon P, Amin K, Steenbergen C, Murphy E, Arcasoy MO. Erythropoietin receptor expression in adult rat cardiomyocytes is associated with an acute cardioprotective effect for recombinant erythropoietin during ischemia-reperfusion injury. FASEB J 2004; 18(9): 1031-3.
[http://dx.doi.org/10.1096/fj.03-1289fje] [PMID: 15059965]
[72]
Chiurchiù V, Lanuti M, De Bardi M, Battistini L, Maccarrone M. The differential characterization of GPR55 receptor in human peripheral blood reveals a distinctive expression in monocytes and NK cells and a proinflammatory role in these innate cells. Int Immunol 2015; 27(3): 153-60.
[http://dx.doi.org/10.1093/intimm/dxu097] [PMID: 25344934]
[73]
Depping R, Kawakami K, Ocker H, et al. Expression of the erythropoietin receptor in human heart. J Thorac Cardiovasc Surg 2005; 130(3): 877-8.
[http://dx.doi.org/10.1016/j.jtcvs.2004.12.041] [PMID: 16153943]
[74]
Anagnostou A, Liu Z, Steiner M, et al. Erythropoietin receptor mRNA expression in human endothelial cells. Proc Natl Acad Sci USA 1994; 91(9): 3974-8.
[http://dx.doi.org/10.1073/pnas.91.9.3974] [PMID: 8171022]
[75]
Naito Y, Sawada H, Oboshi M, et al. Cardiac remodeling in response to chronic iron deficiency: role of the erythropoietin receptor. J Hypertens 2015; 33(6): 1267-75.
[http://dx.doi.org/10.1097/HJH.0000000000000547] [PMID: 25715089]
[76]
Kiss K1, Csonka C2, Pálóczi J, et al. Novel, selective EPO receptor ligands lacking erythropoietic activity reduce infarct size in acute myocardial infarction in rats. Pharmacol Res 2016; 113(Pt A): 62-70.
[77]
Burger D, Lei M, Geoghegan-Morphet N, Lu X, Xenocostas A, Feng Q. Erythropoietin protects cardiomyocytes from apoptosis via up-regulation of endothelial nitric oxide synthase. Cardiovasc Res 2006; 72(1): 51-9.
[http://dx.doi.org/10.1016/j.cardiores.2006.06.026] [PMID: 16904088]
[78]
Calvillo L, Latini R, Kajstura J, et al. Recombinant human erythropoietin protects the myocardium from ischemia-reperfusion injury and promotes beneficial remodeling. Proc Natl Acad Sci USA 2003; 100(8): 4802-6.
[http://dx.doi.org/10.1073/pnas.0630444100] [PMID: 12663857]
[79]
Voors AA, Belonje AM, Zijlstra F, et al. A single dose of erythropoietin in ST-elevation myocardial infarction. Eur Heart J 2010; 31(21): 2593-600.
[http://dx.doi.org/10.1093/eurheartj/ehq304] [PMID: 20802250]
[80]
Kim KH, Oudit GY, Backx PH. Erythropoietin protects against doxorubicin-induced cardiomyopathy via a phosphatidylinositol 3-kinase-dependent pathway. J Pharmacol Exp Ther 2008; 324(1): 160-9.
[http://dx.doi.org/10.1124/jpet.107.125773] [PMID: 17928571]
[81]
Nandra KK, Collino M, Rogazzo M, Fantozzi R, Patel NS, Thiemermann C. Pharmacological preconditioning with erythropoietin attenuates the organ injury and dysfunction induced in a rat model of hemorrhagic shock. Dis Model Mech 2013; 6(3): 701-9.
[http://dx.doi.org/10.1242/dmm.011353] [PMID: 23264564]
[82]
Nishiya D, Omura T, Shimada K, et al. Effects of erythropoietin on cardiac remodeling after myocardial infarction. J Pharmacol Sci 2006; 101(1): 31-9.
[http://dx.doi.org/10.1254/jphs.FP0050966] [PMID: 16717399]
[83]
Parsa CJ, Matsumoto A, Kim J, et al. A novel protective effect of erythropoietin in the infarcted heart. J Clin Invest 2003; 112(7): 999-1007.
[http://dx.doi.org/10.1172/JCI18200] [PMID: 14523037]
[84]
Puchulu MB, Arreche N, Zotta E, et al. Erythropoietin improves cardiovascular function in adult rats after acute hemorrhage. J Cardiovasc Pharmacol 2019; 73(5): 290-300.
[http://dx.doi.org/10.1097/FJC.0000000000000666] [PMID: 31082960]
[85]
Moon C, Krawczyk M, Paik D, Lakatta EG, Talan MI. Cardioprotection by recombinant human erythropoietin following acute experimental myocardial infarction: dose response and therapeutic window. Cardiovasc Drugs Ther 2005; 19(4): 243-50.
[http://dx.doi.org/10.1007/s10557-005-3189-6] [PMID: 16187008]
[86]
Moon C, Krawczyk M, Lakatta EG, Talan MI. Therapeutic effectiveness of a single vs multiple doses of erythropoietin after experimental myocardial infarction in rats. Cardiovasc Drugs Ther 2006; 20(4): 245-51.
[http://dx.doi.org/10.1007/s10557-006-0080-z] [PMID: 17019537]
[87]
Moon C, Krawczyk M, Ahn D, et al. Erythropoietin reduces myocardial infarction and left ventricular functional decline after coronary artery ligation in rats. Proc Natl Acad Sci USA 2003; 100(20): 11612-7.
[http://dx.doi.org/10.1073/pnas.1930406100] [PMID: 14500913]
[88]
Westenbrink BD, Lipsic E, van der Meer P, et al. Erythropoietin improves cardiac function through endothelial progenitor cell and vascular endothelial growth factor mediated neovascularization. Eur Heart J 2007; 28(16): 2018-27.
[http://dx.doi.org/10.1093/eurheartj/ehm177] [PMID: 17576662]
[89]
Lipšic E, van der Meer P, Voors AA, et al. A single bolus of a long-acting erythropoietin analogue darbepoetin alfa in patients with acute myocardial infarction: a randomized feasibility and safety study. Cardiovasc Drugs Ther 2006; 20(2): 135-41.
[http://dx.doi.org/10.1007/s10557-006-7680-5] [PMID: 16761193]
[90]
Werner N, Kosiol S, Schiegl T, et al. Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med 2005; 353(10): 999-1007.
[http://dx.doi.org/10.1056/NEJMoa043814] [PMID: 16148285]
[91]
Zafiriou MP, Noack C, Unsöld B, et al. Erythropoietin responsive cardiomyogenic cells contribute to heart repair post myocardial infarction. Stem Cells 2014; 32(9): 2480-91.
[http://dx.doi.org/10.1002/stem.1741] [PMID: 24806289]
[92]
Bahlmann FH, De Groot K, Spandau JM, et al. Erythropoietin regulates endothelial progenitor cells. Blood 2004; 103(3): 921-6.
[http://dx.doi.org/10.1182/blood-2003-04-1284] [PMID: 14525788]
[93]
Lipšic E, Schoemaker RG, van der Meer P, Voors AA, van Veldhuisen DJ, van Gilst WH. Protective effects of erythropoietin in cardiac ischemia: from bench to bedside. J Am Coll Cardiol 2006; 48(11): 2161-7.
[http://dx.doi.org/10.1016/j.jacc.2006.08.031] [PMID: 17161240]
[94]
Ott I, Schulz S, Mehilli J, et al. Erythropoietin in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: a randomized, double-blind trial. Circ Cardiovasc Interv 2010; 3(5): 408-13.
[http://dx.doi.org/10.1161/CIRCINTERVENTIONS.109.904425] [PMID: 20736448]
[95]
Seo WW, Suh JW, Oh IY, et al. Efficacy of intracoronary erythropoietin delivery before reperfusion-gauging infarct size in patients with acute st-segment elevation myocardial infarction (ICEBERG). Int Heart J 2019; 60(2): 255-63.
[http://dx.doi.org/10.1536/ihj.18-035] [PMID: 30799375]
[96]
Manolis TA, Manolis AA, Melita H, Manolis AS. Sudden unexpected death in epilepsy: The neuro-cardio-respiratory connection. Seizure 2019; 64: 65-73.
[http://dx.doi.org/10.1016/j.seizure.2018.12.007] [PMID: 30566897]
[97]
Grossman A, Messerli FH, Grossman E. Drug induced hypertension-An unappreciated cause of secondary hypertension. Eur J Pharmacol 2015; 763; Pt A: 15-22.
[98]
Jurca SJ, Elliott WJ. Common substances that may contribute to resistant hypertension, and recommendations for limiting their clinical effects. Curr Hypertens Rep 2016; 18(10): 73.
[99]
Kanagy NL, Perrine MF, Cheung DK, Walker BR. Erythropoietin administration in vivo increases vascular nitric oxide synthase expression. J Cardiovasc Pharmacol 2003; 42(4): 527-33.
[http://dx.doi.org/10.1097/00005344-200310000-00011] [PMID: 14508239]
[100]
Bullard AJ, Yellon DM. Chronic erythropoietin treatment limits infarct-size in the myocardium in vitro. Cardiovasc Drugs Ther 2005; 19(5): 333-6.
[http://dx.doi.org/10.1007/s10557-005-4595-5] [PMID: 16382295]
[101]
Tsukahara H, Hiraoka M, Hori C, et al. Chronic erythropoietin treatment enhances endogenous nitric oxide production in rats. Scand J Clin Lab Invest 1997; 57(6): 487-93.
[http://dx.doi.org/10.3109/00365519709084598] [PMID: 9350067]
[102]
Vaziri ND, Zhou XJ, Smith J, et al. In vivo and in vitro pressor effects of erythropoietin in rats. Am J Physiol 1995; 269(6-Pt 2): F838-45.
[103]
Fernando G, Yamila R, Cesar GJ, et al. Neuroprotective effects of neuroepo using an in vitro model of stroke. In: Behav Sci (Basel,Switzerland). 2018; 8:(2:): 26.
[http://dx.doi.org/10.3390/bs8020026]
[104]
Auzmendi J, Buchholz B, Salguero J, et al. Pilocarpine-induced status epilepticus is associated with p-glycoprotein induction in cardiomyocytes, electrocardiographic changes, and sudden death Pharmaceuticals (Basel) 2018. 11(1 pii): E21.
[105]
Auzmendi J, Akyüz E, Lazarowski A. The role of P-glycoprotein (P-gp) and inwardly rectifying potassium (Kir) channels in sudden unexpected death in epilepsy (SUDEP). Epilepsy Behav 2019; 6 106590
[http://dx.doi.org/10.1016/j.yebeh.2019.106590] [PMID: 31706919]
[106]
Auzmendi JA, Orozco-Suárez S, Bañuelos-Cabrera I, et al. Pglycoprotein contributes to cell membrane depolarization of hippocampus and neocortex in a model of repetitive seizures induced by pentylenetetrazole in rats. Curr Pharm Des 2013. 013;19(38): 6732-8.
[107]
Auzmendi J, Merelli A, Girardi E, et al. Progressive heart P-glycoprotein (P-gp) overexpression after experimental repetitive seizures (ERS) associated with fatal status epilepticus (FSE). Is it related with SUDEP? Mol Cell Epilepsy 2014; 1: 43-51.
[108]
Tavares JG, Vasques ER, Arida RM, et al. Epilepsy-induced electrocardiographic alterations following cardiac ischemia and reperfusion in rats. Braz J Med Biol Res 2015; 48(2): 140-5.
[http://dx.doi.org/10.1590/1414-431x20144311] [PMID: 25590352]
[109]
Piwnica-Worms D, Kronauge JF, Chiu ML. Uptake and retention of hexakis (2-methoxyisobutyl isonitrile) technetium(I) in cultured chick myocardial cells. Mitochondrial and plasma membrane potential dependence. Circulation 1990; 82(5): 1826-38.
[http://dx.doi.org/10.1161/01.CIR.82.5.1826] [PMID: 2225379]
[110]
Lazarowski AJ, García Rivello HJ, Vera Janavel GL, et al. Cardiomyocytes of chronically ischemic pig hearts express the MDR-1 gene-encoded P-glycoprotein. J Histochem Cytochem 2005; 53(7): 845-50.
[http://dx.doi.org/10.1369/jhc.4A6542.2005] [PMID: 15995143]
[111]
Laguens RP, Lazarowski AJ, Cuniberti LA, et al. Expression of the MDR-1 gene-encoded P-glycoprotein in cardiomyocytes of conscious sheep undergoing acute myocardial ischemia followed by reperfusion. J Histochem Cytochem 2007; 55(2): 191-7.
[http://dx.doi.org/10.1369/jhc.6A7026.2006] [PMID: 17101727]
[112]
Shmuely S, van der Lende M, Lamberts RJ, Sander JW, Thijs RD. The heart of epilepsy: Current views and future concepts. Seizure 2017; 44: 176-83.
[http://dx.doi.org/10.1016/j.seizure.2016.10.001] [PMID: 27843098]
[113]
Fukuda K, Kanazawa H, Aizawa Y, Ardell JL, Shivkumar K. Cardiac innervation and sudden cardiac death. Circ Res 2015; 116(12): 2005-19.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.304679] [PMID: 26044253]
[114]
Fialho GL, Wolf P, Walz R, Lin K. Epilepsy and ultra-structural heart changes: The role of catecholaminergic toxicity and myocardial fibrosis. What can we learn from cardiology? Seizure 2019; 71: 105-9.
[http://dx.doi.org/10.1016/j.seizure.2019.07.002] [PMID: 31306872]
[115]
Hirata A, Minamino T, Asanuma H, et al. Erythropoietin just before reperfusion reduces both lethal arrhythmias and infarct size via the phosphatidylinositol-3 kinase-dependent pathway in canine hearts. Cardiovasc Drugs Ther 2005; 19(1): 33-40.
[http://dx.doi.org/10.1007/s10557-005-6895-1] [PMID: 15883754]
[116]
Burger DE, Xiang FL, Hammoud L, Jones DL, Feng Q. Erythropoietin protects the heart from ventricular arrhythmia during ischemia and reperfusion via neuronal nitric-oxide synthase. J Pharmacol Exp Ther 2009; 329(3): 900-7.
[http://dx.doi.org/10.1124/jpet.109.150896] [PMID: 19307451]
[117]
Piuhola J, Kerkelä R, Keenan JI, Hampton MB, Richards AM, Pemberton CJ. Direct cardiac actions of erythropoietin (EPO): effects on cardiac contractility, BNP secretion and ischaemia/reperfusion injury. Clin Sci (Lond) 2008; 114(4): 293-304.
[http://dx.doi.org/10.1042/CS20070229] [PMID: 17919123]
[118]
Scorza FA, Arida RM, Cysneiros RM, et al. The brain-heart connection: implications for understanding sudden unexpected death in epilepsy. Cardiol J 2009; 16(5): 394-9.
[PMID: 19753516]
[119]
Surges R, Adjei P, Kallis C, et al. Pathologic cardiac repolarization in pharmacoresistant epilepsy and its potential role in sudden unexpected death in epilepsy: a case-control study. Epilepsia 2010; 51(2): 233-42.
[http://dx.doi.org/10.1111/j.1528-1167.2009.02330.x] [PMID: 19817816]
[120]
Leutmezer F, Schernthaner C, Lurger S. et al.Electrocardiographic changes at the onset of epileptic . Epilepsia 2003; 44(2): 348-54.
[121]
Mayer H, Benninger F, Urak L, Plattner B, Geldner J, Feucht M. EKG abnormalities in children and adolescents with symptomatic temporal lobe epilepsy. Neurology 2004; 63(2): 324-8.
[http://dx.doi.org/10.1212/01.WNL.0000129830.72973.56] [PMID: 15277628]
[122]
Almansori M, Ijaz M, Ahmed SN. Cerebral arrhythmia influencing cardiac rhythm: a case of ictal bradycardia. Seizure 2006; 15(6): 459-61.
[http://dx.doi.org/10.1016/j.seizure.2006.05.008] [PMID: 16798021]
[123]
Altenmüller DM, Zehender M, Schulze-Bonhage A. High-grade atrioventricular block triggered by spontaneous and stimulation-induced epileptic activity in the left temporal lobe. Epilepsia 2004; 45(12): 1640-4.
[http://dx.doi.org/10.1111/j.0013-9580.2004.34403.x] [PMID: 15571524]
[124]
Holst AG, Winkel BG, Risgaard B, et al. Epilepsy and risk of death and sudden unexpected death in the young: a nationwide study. Epilepsia 2013; 54(9): 1613-20.
[http://dx.doi.org/10.1111/epi.12328] [PMID: 23895621]
[125]
Nashef L. Sudden unexpected death in epilepsy: terminology and definitions. Epilepsia 1997; 38(11)(Suppl.): S6-8.
[http://dx.doi.org/10.1111/j.1528-1157.1997.tb06130.x] [PMID: 19909329]
[126]
Barrie N, Manolios N. The endocannabinoid system in pain and inflammation: Its relevance to rheumatic disease. Eur J Rheumatol 2017; 4(3): 210-8.
[http://dx.doi.org/10.5152/eurjrheum.2017.17025] [PMID: 29164003]
[127]
Tang F, Hartz AMS, Bauer B. Drug-resistant epilepsy: multiple hypotheses, few answers. Front Neurol 2017; 8: 301.
[http://dx.doi.org/10.3389/fneur.2017.00301] [PMID: 28729850]
[128]
Tishler DM, Weinberg KI, Hinton DR, Barbaro N, Annett GM, Raffel C. MDR1 gene expression in brain of patients with medically intractable epilepsy. Epilepsia 1995; 36(1): 1-6.
[http://dx.doi.org/10.1111/j.1528-1157.1995.tb01657.x] [PMID: 8001500]
[129]
Lazarowski A, Sevlever G, Taratuto A, Massaro M, Rabinowicz A. Tuberous sclerosis associated with MDR1 gene expression and drug-resistant epilepsy. Pediatr Neurol 1999; 21(4): 731-4.
[http://dx.doi.org/10.1016/S0887-8994(99)00074-0] [PMID: 10580886]
[130]
Lazarowski A, Ramos AJ, García-Rivello H, Brusco A, Girardi E. Neuronal and glial expression of the multidrug resistance gene product in an experimental epilepsy model. Cell Mol Neurobiol 2004; 24(1): 77-85.
[http://dx.doi.org/10.1023/B:CEMN.0000012726.43842.d2] [PMID: 15049512]
[131]
Darling RJ, Kuchibhotla U, Glaesner W, Micanovic R, Witcher DR, Beals JM. Glycosylation of erythropoietin affects receptor binding kinetics: role of electrostatic interactions. Biochemistry 2002; 41(49): 14524-31.
[http://dx.doi.org/10.1021/bi0265022] [PMID: 12463751]

Rights & Permissions Print Cite
Article Metrics
33
7
World Health Day
© 2024 Bentham Science Publishers | Privacy Policy