nach oben

Erschienen in:

01.11.2012 | Basic Neurosciences, Genetics and Immunology - Original Article

Erythropoietin reverts cognitive impairment and alters the oxidative parameters and energetic metabolism in sepsis animal model

verfasst von: Clarissa M. Comim, Omar J. Cassol Jr., Igor Abreu, Thais Moraz, Larissa S. Constantino, Francieli Vuolo, Letícia S. Galant, Natália de Rochi, Meline O. dos Santos Morais, Giselli Scaini, Tatiana Barichello, Emílio L. Streck, João Quevedo, Felipe Dal-Pizzol

Erschienen in: Journal of Neural Transmission | Ausgabe 11/2012

Einloggen, um Zugang zu erhalten

Abstract

Sepsis is characterized by systemic biochemical alterations including the central nervous system in the early times and cognitive impairment at later times after sepsis induction in the animal model. Recent studies have shown that, besides its hematological activity, erythropoietin (EPO) has cytoprotective effects on various cells and tissues. In order to corroborate elucidating the effects of alternative drugs for sepsis treatment, we evaluated the effects of both acute and chronic EPO treatment on oxidative stress and energetic metabolism in the hippocampus, and cognitive impairment, respectively, after sepsis induction by cecal ligation and perforation (CLP). To this aim, male Wistar rats underwent CLP with “basic support” or sham operation. In the acute treatment, EPO was administered once immediately after CLP induction. The rats were then killed after 6 and 24 h, and the hippocampus was removed for analysis of oxidative stress and energetic metabolism, respectively. Regarding the chronic treatment, EPO was administered once daily until the 4th day after induction. Aversive memory was tested on the 10th day after surgery. It was observed that the acute use of EPO (a single dose) alters the oxidative parameters and energetic metabolism. Chronic use (4 days) reversed cognitive impairment in the sepsis animal model. Mortality rates were attenuated only during chronic treatment.

Abdelrahman M, Rafi A, Ghacha R, Qayyum T, Karkar A (2004) Post-transplant erythrocytosis: a review of 47 renal transplant recipients. Saudi J Kidney Dis Transpl (an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia) 4:433–439

Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126PubMedCrossRef

Akimoto T, Kusano E, Muto S, Fujita N, Okada K, Saito T, Komatsu N, Ono S, Ebata S, Ando Y, Homma S, Asano Y (1999) The effect of erythropoietin on interleukin-1beta mediated increase in nitric oxide synthesis in vascular smooth muscle cells. J hypertens 9:1249–1256CrossRef

Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR (2001) Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 29:1303–1310PubMedCrossRef

Aoshiba K, Onizawa S, Tsuji T, Nagai A (2009) Therapeutic effects of erythropoietin in murine models of endotoxin shock. Crit Care Med 37:889–898PubMedCrossRef

Ates E, Yalcin AU, Yilmaz S, Koken T, Tokyol C (2005) Protective effect of erythropoietin on renal ischemia and reperfusion injury. ANZ J Surg 75:1100–1105PubMedCrossRef

Bannister JV, Calabrese L (1987) Assays for superoxide dismutase. Methods Biochem Anal 32:279–312PubMedCrossRef

Barichello T, Martins MR, Reinke A, Feier G, Ritter C, Quevedo J, Dal-Pizzol F (2005) Cognitive impairment in sepsis survivors from cecal ligation and perforation. Crit Care Med 33:221–223PubMedCrossRef

Barichello T, Fortunato JJ, Vitali AM, Feier G, Reinke A, Moreira JC, Quevedo J, Dal-Pizzol F (2006) Oxidative variables in the brain after sepsis induced by cecal ligation and perforation. Crit Care Med 34:886–889PubMedCrossRef

Bohlius J, Schmidlin K, Brillant C, Schwarzer G, Trelle S, Seidenfeld J, Zwahlen M, Clarke M, Weingart O, Kluge S, Piper M, Rades D, Steensma DP, Djulbegovic B, Fey MF, Ray-Coquard I, Machtay M, Moebus V, Thomas G, Untch M, Schumacher M, Egger M, Engert A (2009) Recombinant human erythropoiesis-stimulating agents and mortality in patients with cancer: a meta-analysis of randomized trials. Lancet 373:1532–1542PubMedCrossRef

Cain SM, Curtis SE (1991) Experimental models of pathologic oxygen supply dependency. Crit Care Med 19:603–612PubMedCrossRef

Calapai G, Marciano MC, Corica F, Allegra A, Parisi A, Frisina N, Caputi AP, Buemi M (2000) Erythropoietin protects against brain ischemic injury by inhibition of nitric oxide formation. Eur J Pharmacol 401:349–356PubMedCrossRef

Cassina A, Radi R (1996) Differential inhibitory action of nitric oxide and peroxynitrite on mitochondrial electron transport. Arch Biochem Biophys 328:309–316PubMedCrossRef

Chandra V, Pandav R, Laxminarayan R, Tanner C, Manyam B, Rajkumar S, Silberberg D, Brayne C, Chow J, Herman S, Hourihan F, Kasner S, Morillo L, Ogunniyi A, Theodore W, Zhang ZX (2006) Neurological disorders. In: Jamison DT, Breman JG, Measham AR, Alleyne G, Claeson M, Evans DB, Jha P, Mills A, Musgrove P (eds) Disease control priorities in developing countries, 2nd edn. World Bank, Washington, DC

Chao CC, Hu S, Peterson PK (1995) Glia, cytokines, and neurotoxicity. Crit Rev Neurobiol 9:189–205PubMed

Comim CM, Rezin GT, Scaini G, Di-Pietro PB, Cardoso MR, Petronilho FC, Ritter C, Streck EL, Quevedo J, Dal-Pizzol F (2008) Mitochondrial respiratory chain and creatine kinase activities in rat brain after sepsis induced by cecal ligation and perforation. Mitochondrion 8:313–318PubMedCrossRef

Comim CM, Constantino LC, Barichello T, Streck EL, Quevedo J, Dal-Pizzol F (2009) Cognitive impairment in the septic brain. Curr Neurovasc Res 6:194–203PubMedCrossRef

Comim CM, Cassol-Jr OJ, Constantino LC, Petronilho F, Constantino LS, Stertz L, Kapczinski F, Barichello T, Quevedo J, Dal-Pizzol F (2010) Depressive-like parameters in sepsis survivor rats. Neurotoxic Res 17:279–286CrossRef

Comim CM, Cassol-Jr OJ, Constantino LS, Felisberto F, Petronilho F, Rezin GT, Scaini G, Daufenbach JF, Streck EL, Quevedo J, Dal-Pizzol F (2011) Alterations in inflammatory mediators, oxidative stress parameters and energetic metabolism in the brain of sepsis survivor rats. Neurochem Res 36:304–311PubMedCrossRef

Cuzzocrea S, Di PR, Mazzon E, Patel NS, Genovese T, Muia C, Crisafulli C, Caputi AP, Thiemermann C (2006) Erythropoietin reduces the development of nonseptic shock induced by zymosan in mice. Crit Care Med 34:1168–1177PubMedCrossRef

Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL (2008) Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 36:296–327PubMedCrossRef

Digicaylioglu M, Bichet S, Marti HH, Wenger RH, Rivas LA, Bauer C, Gassmann M (1995) Localization of specific erythropoietin binding sites in defined areas of the mouse brain. Proc Natl Acad Sci USA 9:3717–3720CrossRef

Ehrenreich H, Degner D, Meller J, Brines M, Béhé M, Hasselblatt M, Woldt H, Falkai P, Knerlich F, Jacob S, von Ahsen N, Maier W, Brück W, Rüther E, Cerami A, Becker W, Sirén AL (2004) Erythropoietin: a candidate compound for neuroprotection in schizophrenia. Mol Psychiatry 9:42–54PubMed

Ehrenreich H, Weissenborn K, Prange H, Schneider D, Weimar C, Wartenberg K, Schellinger PD, Bohn M, Becker H, Wegrzyn M, Jähnig P, Herrmann M, Knauth M, Bähr M, Heide W, Wagner A, Schwab S, Reichmann H, Schwendemann G, Dengler R, Kastrup A, Bartels C, EPO Stroke Trial Group (2009) Recombinant human erythropoietin in the treatment of acute ischemic stroke. Stroke 40:e647–e656PubMedCrossRef

Esterbauer H, Cheeseman KH (1990) Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. Methods Enzymol 186:407–421PubMedCrossRef

Farrell F, Lee A (2004) The erythropoietin receptor and its expression in tumor cells and other tissues. Oncologist 5:18–30CrossRef

Fauchère JC, Dame C, Vonthein R, Koller B, Arri S, Wolf M, Bucher HU (2008) An approach to using recombinant erythropoietin for neuroprotection in very preterm infants. Pediatrics 122:375–382PubMedCrossRef

Fischer JC, Ruitenbeek W, Berden JA, Trijbels JM, Veerkamp JH, Stadhouders AM, Sengers RC, Janssen AJ (1985) Differential investigation of the capacity of succinate oxidation in human skeletal muscle. Clin Chim Acta 153:23–36PubMedCrossRef

Floyd RA (1999) Antioxidants, oxidative stress, and degenerative neurological disorders. Proc Soc Exp Biol Med 222:236–245PubMedCrossRef

Harris KW, Winkelmann JC (1996) Enzyme-linked immunosorbent assay detects a potential soluble form of the erythropoietin receptor in human plasma. Am J Hematol 52:8–13PubMedCrossRef

Hu S, Peterson PK, Chao CC (1997) Cytokine-mediated neuronal apoptosis. Neurochem Int 30:427–431PubMedCrossRef

Hughes BP (1962) A method for the estimation of serum creatine kinase and its use in comparing creatine kinase and aldolase activity in normal and pathological sera. Clin Chim Acta 7:597–603PubMedCrossRef

Iwashyna TJ, Ely EW, Smith DM, Langa KM (2010) Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA 304:1787–1794PubMedCrossRef

Jelkmann W (1992) Erythropoietin: structure, control of production, and function. Physiol Rev 2:449–489

Kafa IM, Uysal M, Bakirci S, Ayberk Kurt M (2010) Sepsis induces apoptotic cell death in different regions of the brain in a rat model of sepsis. Acta Neurobiol Exp 70:246–260

Levine RL, Williams JA, Stadtman ER, Shacter E (1994) Carbonyl assays for determination of oxidatively modified proteins. Methods Enzymol 233:346–357PubMedCrossRef

Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193:265–275PubMed

Maiese K, Li F, Chong ZZ (2004) Erythropoietin in the brain: can the promise to protect be fulfilled? Trends Pharmacol Sci 11:577–583CrossRef

Marshall JC, Deitch C, Moldawer LL, Opal S, Redl H, Van der Poll T (2005) Preclinical models of shock and sepsis: what can they tell us? Shock 24:1–6PubMedCrossRef

Messaris E, Memos N, Chatzigianni E, Konstadoulakis MM, Menenakos E, Katsaragakis S, Voumvourakis C, Androulakis G (2004) Time-dependent mitochondrial-mediated programmed neuronal cell death prolongs survival in sepsis. Crit Care Med 32:1764–1770PubMedCrossRef

Miro O, Cardellach F, Barrientos A, Casademont J, Rotig A, Rustin P (1998) Cytochrome c oxidase assay in minute amounts of human skeletal muscle using single wavelength spectrophotometers. J Neurosci Methods 80:107–111PubMedCrossRef

Mitra A, Bansal S, Wang W, Falk S, Zolty E, Schrier RW (2007) Erythropoietin ameliorates renal dysfunction during endotoxaemia. Nephrol Dial Transplant 22:2349–2353PubMedCrossRef

Nelson DP, Samsel RW, Wood LDH, Schumacker PT (1988) Pathological supply dependence of systemic and intestinal O₂ uptake during endotoxemia. J Appl Physiol 64:2410–2419PubMed

Quevedo J, Vianna MR, Roesler R, Izquierdo I (1999) Two time windows of anisomycin-induced amnesia for inhibitory avoidance training in rats: protection from amnesia by pretraining but not pre-exposure to the task apparatus. Learn Mem 6:600–607PubMedCrossRef

Rietschel ET, Brade H, Holst O, Brade L, Müller-Loennies S, Mamat U, Zähringer U, Beckmann F, Seydel U, Brandenburg K, Ulmer AJ, Mattern T, Heine H, Schletter J, Loppnow H, Schönbeck U, Flad HD, Hauschildt S, Schade UF, Di Padova F, Kusumoto S, Schumann RR (1996) Bacterial endotoxin: chemical constitution, biological recognition, host response, and immunological detoxification. Curr Top Microbiol Immunol 216:39–81PubMedCrossRef

Sands KE, Bates DW, Lanken PN, Graman PS, Hibberd PL, Kahn KL, Parsonnet J, Panzer R, Orav EJ, Snydman DR, Black E, Schwartz JS, Moore R, Johnson BL, Platt R (1997) Academic Medical Center Consortium Sepsis Project Working Group: epidemiology of sepsis syndrome in 8 academic medical centers. JAMA 278:234–238PubMedCrossRef

Semmler A, Okulla T, Sastre M, Dumitrescu-Ozimek L, Heneka MT (2005) Systemic inflammation induces apoptosis with variable vulnerability of different brain regions. J Chem Neuroanat 30:144–157PubMedCrossRef

Sharples EJ, Yaqoob MM (2006) Erythropoietin and acute renal failure. Sem Nephrol 4:325–331CrossRef

Sharples EJ, Patel N, Brown P, Stewart K, Mota-Philipe H, Sheaff M, Kieswich J, Allen D, Harwood S, Raftery M, Thiemermann C, Yaqoob MM (2004) Erythropoietin protects the kidney against the injury and dysfunction caused by ischemia–reperfusion. J Am Soc Nephrol 15:2115–2224PubMedCrossRef

Sølling C, Christensen AT, Nygaard U, Krag S, Frøkiaer J, Wogensen L, Krog J, Tønnesen EK (2011a) Erythropoietin does not attenuate renal dysfunction or inflammation in a porcine model of endotoxemia. Acta Anaesthesiol Scand 55(4):411–421PubMedCrossRef

Sølling C, Nygaard U, Christensen AT, Wogensen L, Krog J, Tønnesen EK (2011b) Lymphocyte apoptosis is resistant to erythropoietin in porcine endotoxemia. APMIS 119:143–154PubMedCrossRef

Sprung CL, Peduzzi PN, Shatney CH, Schein RM, Wilson MF, Sheagren JN, Hinshaw LB (1990) Impact of encephalopathy on mortality in the sepsis syndrome. The Veterans Administration Systemic Sepsis Cooperative Study Group. Crit Care Med 18:801–806PubMedCrossRef

Squadrito F, Altavilla D, Squadrito G, Campo GM, Arlotta M, Quartarone C, Saitta A, Caputi AP (1999) Recombinant human erythropoietin inhibits iNOS activity and reverts vascular dysfunction in splanchnic artery occlusion shock. Br J Pharmacol 2:482–488CrossRef

Srere PA (1969) Citrate synthase. Methods Enzymol 13:3–11CrossRef

Streck EL, Comim CM, Barichello T, Quevedo J (2008) The septic brain. Neurochem Res 33:2171–2177PubMedCrossRef

Tonelli M, Hemmelgarn B, Reiman T, Manns B, Reaume MN, Lloyd A, Wiebe N, Klarenbach S (2009) Benefits and harms of erythropoiesis-stimulating agents for anemia related to cancer: a meta-analysis. CMAJ 180:E62–E71PubMedCrossRef

Tuon L, Comim CM, Petronilho F, Barichello T, Izquierdo I, Quevedo J, Dal-Pizzol F (2008) Time-dependent behavioral recovery after sepsis in rats. Intensive Care Med 34:1724–1731PubMedCrossRef

Vandijck D, Decruyenaere JM, Blot SI (2006) The value of sepsis definitions in daily ICU-practice. Acta Clin Belg 6:220–226

Vesey DA, Cheung C, Pat B, Endre Z, Gobe G, Johnson DW (2004) Erythropoietin protects against ischaemic acute renal injury. Nephrol Dial Transplant 19:348–355CrossRef

Westenfelder C, Dl Biddle, Rl Baranowski (1999) Human, rat, and mouse kidney cells express functional erythropoietin receptors. Kidney Int 3:808–820CrossRef

Wu ZS, Zhou GZ, Jiang JH, Shen GL, Yu RQ (2006) Gold colloid-bienzyme conjugates for glucose detection utilizing surface-enhanced Raman scattering. Talanta 3:533–539CrossRef

Yamaji R, Okada T, Moriya M, Naito M, Tsuruo T, Miyatake K, Nakano Y (1996) Brain capillary endothelial cells express two forms of erythropoietin receptor mRNA. Eur J Biochem 239:494–500PubMedCrossRef

Yamamoto M, Koshimura K, Sohmiya M, Murakami Y, Kato Y (2004) Effect of erythropoietin on nitric oxide production in the rat hippocampus using in vivo brain microdialysis. Neuroscience 128:163–168PubMedCrossRef

Young GB, Bolton CF, Austin TW, Archibald YM, Gonder J, Wells GA (1990) The encephalopathy associated with septic illness. Clin Invest Med 13:297–304PubMed

Titel: Erythropoietin reverts cognitive impairment and alters the oxidative parameters and energetic metabolism in sepsis animal model
verfasst von: Clarissa M. Comim
Omar J. Cassol Jr.
Igor Abreu
Thais Moraz
Larissa S. Constantino
Francieli Vuolo
Letícia S. Galant
Natália de Rochi
Meline O. dos Santos Morais
Giselli Scaini
Tatiana Barichello
Emílio L. Streck
João Quevedo
Felipe Dal-Pizzol
Publikationsdatum: 01.11.2012
Verlag: Springer Vienna
Erschienen in: Journal of Neural Transmission / Ausgabe 11/2012
Print ISSN: 0300-9564
Elektronische ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-012-0774-2

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Akuter Schwindel: Wann lohnt sich eine MRT?

28.04.2024 Schwindel Nachrichten

Akuter Schwindel stellt oft eine diagnostische Herausforderung dar. Wie nützlich dabei eine MRT ist, hat eine Studie aus Finnland untersucht. Immerhin einer von sechs Patienten wurde mit akutem ischämischem Schlaganfall diagnostiziert.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Frühe Alzheimertherapie lohnt sich

25.04.2024 AAN-Jahrestagung 2024 Nachrichten

Ist die Tau-Last noch gering, scheint der Vorteil von Lecanemab besonders groß zu sein. Und beginnen Erkrankte verzögert mit der Behandlung, erreichen sie nicht mehr die kognitive Leistung wie bei einem früheren Start. Darauf deuten neue Analysen der Phase-3-Studie Clarity AD.

Viel Bewegung in der Parkinsonforschung

25.04.2024 Parkinson-Krankheit Nachrichten

Neue arznei- und zellbasierte Ansätze, Frühdiagnose mit Bewegungssensoren, Rückenmarkstimulation gegen Gehblockaden – in der Parkinsonforschung tut sich einiges. Auf dem Deutschen Parkinsonkongress ging es auch viel um technische Innovationen.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 11/2012

Changes in insulin-signaling transduction pathway underlie learning/memory deficits in an Alzheimer’s disease rat model

The 5-HT1A-receptor agonist flibanserin reduces drug-induced dyskinesia in RGS9-deficient mice

Essential tremor: is it a neurodegenerative disease? No

Huntington’s disease from the patient, caregiver and physician’s perspectives: three sides of the same coin?

Chronic isolation stress compromises JNK/c-Jun signaling in rat brain