Peran Eritropoietin pada Stroke Iskemik Akut

Lisda Amalia, Gilang Nispu Saputra

Abstract


Stroke iskemik merupakan salah satu penyebab stroke tersering, disebabkan oleh oklusi pembuluh darah serebral dan penyebab kematian ketiga. Iskemik otak akan menghasilkan penghasilan mediator inflamasi yang dapat berpartisipasi dalam jejas iskemik di otak. Saat awitan stroke iskemik terjadi, area otak yang diperdarahi oleh pembuluh darah akan kekurangan oksigen dan nutrisi sehingga sel otak terutama neuron berada dalam risiko, neuron ini masih dapat berfungsi yang dikenal sebagai penumbra. Hipoksia jaringan dan iskemik serebral mengaktivasi HIF-1α, yang kemudian mengaktivasi transkripsi gen eritropoietin (EPO) dan Vascular Endothelial Growth Factor (VEGF). Eritropoietin (EPO) merupakan peptida yang juga memiliki efek non–hematopoiesis yaitu berperan mendorong neuroproteksi. Eritropoietin (EPO)  dikeluarkan dalam hitungan menit dari proses iskemik dan mencapai puncak dalam 24 jam dari awitan stroke iskemik. Efek neuroproteksi dari  EPO yaitu sebagai anti apoptosis, anti oksidan, anti inflamasi, anti eksitoksisitas, neurogenesis, angiogenesis dan neurotropik. Dengan kata lain bahwa EPO dapat mengurangi derajat keparahan akibat oklusi pembuluh darah otak.

 

Role of Eritropoietin in Acute Ischemic Stroke

Abstract

Ischemic stroke is one of the most common causes of stroke, caused by cerebral vascular occlusion and the third cause of death. . Ischemic brain will generate income of inflammatory mediators who can participate in ischemic lesions in the brain. When the recitation of an ischemic stroke occurs, areas of the brain that are obscurated by blood vessels will lack oxygen and nutrients so that brain cells, especially neurons, are at risk, these neurons can still function known as penumbra. Tissue hypoxia and cerebral ischemic activate HIF-1α, which then activates the transcription of the Eritropietin (EPO) and Vascular Endothelial Growth Factor (VEGF) genes. Eritropoietin (EPO) is a peptide that also has the effect of non-hematopoiesis which is responsible for encouraging neuroprotection. Eritropietin (EPO) is issued in minutes of an ischemic process and reaches its peak within 24 hours of the onset ischemic stroke. The neuroprotection effect of EPO is as anti-apoptosis, anti-oxidant, anti-inflammatory, anti-excitation, neurogenesis, angiogenesis and neurotropic. In other words, EPO can reduce the severity due to occlusion of brain blood vessels.


Keywords


eritropoietin; neuroproteksi; stroke iskemik; eritropietin; ischemic stroke;, neuroprotection

Full Text:

PDF

References


Mestre H, Minian YC, Fainsod DZ. Ibara A. Pharmacological treatment of acute ischemic stroke.Intech Open Science. 2013. Hal 581-614

Hasil Utama Riset Kesehatan Dasar 2018. Jakarta: Kementrian Kesehatan Bdan Penelitian dan Pengembangan Kesehatan. 2018; 53.

Mahulae JX, Ilyas J. Determinan variasi klaim penyakit stroke peserta jaminan kesehatan nasional rumah sakit x sumatera utara. Jurnal Ekonomi Kesehatan Indonesia. Volume 2 Nomor 2. 2017. Hal 76-81.

Wappler EA, Felszeghy K, Varshney M, Mehra RD, Nyakas Csaba, dkk. Brain plasticity following ischemia.Dalam: Balestrino M., editor. Advances in the preclinical study of ischemic stroke. Edited by Maurizio Balestrino.Rijeka, 2012. Hal 89-114.

Fann DYW, Lee SY, Manzanero S, Chunduri P, Sobey CG, Arumugam T V. Pathogenesis of acute stroke and the role of inflammasomes. Ageing Res Rev 2013;12(4):941–66.

Subirós N, García D, Coro-antich RM. Erythropoietin : still on the neuroprotection road. 2012;161–73.

Lo EH, Dalkara T, Moskowitz MA. Neurological diseases: Mechanisms, challenges and opportunities in stroke. Nat Rev Neurosci. 2003;4(5):399–414.

Simats A, García-Berrocoso T, Montaner J. Neuroinflammatory biomarkers: From stroke diagnosis and prognosis to therapy. Biochim Biophys Acta - Mol Basis Dis. 2016;1862(3):411–24.

Lai TW, Zhang S, Wang YT. Excitotoxicity and stroke: Identifying novel targets for neuroprotection. Prog Neurobiol. 2014;115(C):157–88.

Liu XQ, Sheng R, Qin ZH. The neuroprotective mechanism of brain ischemic preconditioning. Acta Pharmacol Sin. 2009;30(8):1071–80.

Aberg ND, Stanne TM, Jood K, Schioler L,dkk. Serum erythropoietin and outcome after ischemic stroke: a prospective study.British Medical Journal; 2015. 1-9

Digicaylioglu M. Erythropoietin in stroke: quo vadis. Expert Opin Biol Ther. 2010;10(6):937–49.

Sucharew H, Khoury J, Moomaw CJ, Alwell K, Kissela BM, Belagaje S, et al. Profiles of the National Institutes of Health Stroke Scale Items as a Predictor of Patient Outcome. Stroke. 2013;44:2182-7.

Carbonell T, Rama R. Iron, Oxidative Stress and Early Neurological Deterioration in Ischemic Stroke. Curr Med Chem. 2007;14(8):857–74.

Merali Z, Huang K, Mikulis D, Silver F, Kassner A. Evolution of blood-brain-barrier permeability after acute ischemic stroke. PLoS One. 2017;12(2):1–11.

Dirnagl U, Simon RP, Hallenbeck JM. Ischemic tolerance and endogenous neuroprotection. Trends Neurosci. 2003;26(5):248–54.

Rodrigo R, Fernandez-Gajardo R, Gutierrez R, Matamala J, Carrasco R, Miranda-Merchak A, dkk. Oxidative Stress and Pathophysiology of Ischemic Stroke: Novel Therapeutic Opportunities. CNS Neurol Disord - Drug Targets. 2013;12(5):698–714.

MA Mohammed, Almuitari A, Gong Chen, Xu Yuexian, Chang Yanzhong, Shi Honglian Factors controlling permeability of the bloof brain brarier. Cellular and Molecular Sciences. Springer 2015. Hal 57-77.

Gu G, Li Y, Peng Z, Xu J, Kang Z, dkk. Mechanism of ischemic tolerance induced by hyperbaric oxygen preconditioning involves up regulation of hypoxia inducible factor 1 alpha and eritropoietin in rats. Journal Appication Physiology. 2008; 104: 1185-91.

Fornage M, Chiang YA, Omeara ES, Psaty BM, Reiner AP, Siscovick DS,dkk. Biomarkers of inflammation and MRI-defined small vessel disease of the brain: The cardiovascular health study. Stroke. 2008;39(7):1952–9.

Czernicki Z, Baethman A, Ito U. Acta Neurochirurgica Supplementum 106 Brain Edema XV. Vol. 106, Acta Neurochirurgica Supplementum. 2010.

Omolara O, Ogunshala , Bogdanova AY. Epo and non hematopoietic cells: what do we know?. Tissue Protective Cytokines: Methods and Protocol. Springer Science. 2013.

Juul S, Pet G. The potential of erythropoietin to treat asphyxia in newborns. Res Reports Neonatol. 2014;Volume 4:195.

Brines M, Cerami A. Erratum: Emerging biological roles for erythropoietin in the nervous system. Nat Rev Neurosci. 2005;6(6):484–94.

Iron F, Requires R. involved . Following a proposal of Roberts and Bomford, Konijn and colleagues reported that inhibitors of 2006;291.

García-Yébenes I, Sobrado M, Moraga A, Zarruk JG, Romera VG, Pradillo JM dkk. Iron overload, measured as serum ferritin, increases brain damage induced by focal ischemia and early reperfusion. Neurochem Int. 2012;61(8):1364–9.

Lemus-Varela ML, Flores-Soto ME, Cervantes-Munguía R, Torres-Mendoza BMG, Gudiño-Cabrera G, Chaparro-Huerta V,dkk. Expression of HIF-1α, VEGF and EPO in peripheral blood from patients with two cardiac abnormalities associated with hypoxia. Clin Biochem. 2010;43(3):234–9.

Thompson JW, Dawson VL, Perez-Pinzon MA, Dawson TM. Intracellular Signaling: Mediators and Protective Responses. Mediators and Protective Responses. Sixth Edit. Stroke: Pathophysiology, Diagnosis, and Management. 2015. 80-89 p.

Brines M, Cerami A. Erythropoietin-mediated tissue protection: Reducing collateral damage from the primary injury response. J Intern Med. 2008;264(5):405–32.

Brines ML, Ghezzi P, Keenan S, Agnello D, de Lanerolle NC, Cerami C,dkk. Erythropoietin crosses the blood-brain barrier to protect against experimental brain injury. Proc Natl Acad Sci. 2000;97(19):10526–31.

Wang B, Kang M, Marchese M, Rodriguez E, Lu W, Li X,dkk. Beneficial Effect of Erythropoietin Short Peptide on Acute Traumatic Brain Injury. Neurotherapeutics. 2016;13(2):418–27.

Puspitasari V, Wahid S, Aliah A, Suhadi B, Kaelan C, As’ad S,dkk. Serum vascular endothelial growth factor as a predictor of clinical outcomes in anterior circulation ischemic stroke. Med J Indones. 2015;24(2):109–14.

Yip H-K, Tsai T-H, Lin H-S, Chen S-F, Sun C-K, Leu S,dkk. Effect of erythropoietin on level of circulating endothelial progenitor cells and outcome in patients after acute ischemic stroke. Crit Care. 2011;15(1):R40.

Lyden P. Using the National Institutes of Health Stroke Scale - A Cautionary Tale. Stroke. 2017;48:513-9.

Gajurel BP, Dhungana K, Parajuli P, Karn R, Rajbhandari R, Kafle D, et al. The National Institute of Health Stroke Scale Score and Outcome in Acute Ischemic Stroke. Journal of Institute of Medicine. 2014.

Agis D, Goggins MB, Oishi K, Oishi K, Davis C, Wright A, et al. Picturing the Size and Site of Stroke With an Expanded National Institutes of Health Stroke Scale. Stroke. 2016;47:1459-564.

Kementrian Kesehatan Republik Indonesia. Pedoman Pengendalian Stroke: Kementrian Kesehatan Republik Indonesia; 2013.42-4

Dahlan M. Sopiyudin. Pintu gerbang memahami epidemiologi, biostatistik dan metode penelitian. Epidemiologi indonesia. Edisi 2. Jakarta, 2017.

Iqbal F, Hussain S, Hassan M. Hypertension, Diabetes Mellitus, and Hypercholesterolaemia as Risk Factors for Stroke. Pakistan J Med Res. 2003;42(1).




DOI: https://doi.org/10.24244/jni.v9i2.262

Refbacks

  • There are currently no refbacks.


                                    

 

JNI is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License