Quantitative proteomic characterization of microvesicles/exosomes from the cerebrospinal fluid of patients with acute bilirubin encephalopathy
- Authors:
- Ning Tan
- Shuiwang Hu
- Zhen Hu
- Zhouli Wu
- Bin Wang
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Affiliations: Department of Pediatrics, Zhujiang Hospital, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510280, P.R. China, Guangdong Provincial Key Laboratory of Proteomics, Department of Pathophysiology, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, National and Local Joint Engineering Laboratory for High‑through Molecular Diagnosis Technology, Translational Medicine Institute, Collaborative Research Center for Post‑doctoral Mobile Stations of Central South University, Affiliated The First People's Hospital of Chenzhou, Southern Medical University, University of South China, Chenzhou, Hunan 423000, P.R. China, Department of Neonatology, Affiliated The First People's Hospital of Chenzhou, Southern Medical University, University of South China, Chenzhou, Hunan 423000, P.R. China - Published online on: May 28, 2020 https://doi.org/10.3892/mmr.2020.11194
- Pages: 1257-1268
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Copyright: © Tan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
This article is mentioned in:
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Bhutani VK, Stark AR, Lazzeroni LC, Poland R, Gourley GR, Kazmierczak S, Meloy L, Burgos AE, Hall JY and Stevenson DK: Predischarge screening for severe neonatal hyperbilirubinemia identifies infants who need phototherapy. J Pediatr. 162:477–482.e1. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Bech LF, Donneborg ML, Lund AM and Ebbesen F: Extreme neonatal hyperbilirubinemia, acute bilirubin encephalopathy, and kernicterus spectrum disorder in children with galactosemia. Pediatr Res. 84:228–232. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Bahr TM, Christensen RD, Agarwal AM, George TI and Bhutani VK: The neonatal acute bilirubin encephalopathy registry (NABER): Background, aims, and protocol. Neonatology. 115:242–246. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Christensen RD, Agarwal AM, George TI, Bhutani VK and Yaish HM: Acute neonatal bilirubin encephalopathy in the state of utah 2009–2018. Blood Cells Mol Dis. 72:10–13. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
McGillivray A and Evans N: Severe neonatal jaundice: Is it a rare event in Australia? J Paediatr Child Health. 48:801–807. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Olusanya BO, Kaplan M and Hansen TWR: Neonatal hyperbilirubinaemia: A global perspective. Lancet Child Adolesc Health. 2:610–620. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Diala UM, Wennberg RP, Abdulkadir I, Farouk ZL, Zabetta CDC, Omoyibo E, Emokpae A, Aravkin A, Toma B, Oguche S, et al On behalf of the Stop Kernicterus In Nigeria (SKIN) study group, : Patterns of acute bilirubin encephalopathy in Nigeria: A multicenter pre-intervention study. J Perinatol. 38:873–880. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Morioka I, Nakamura H, Koda T, Yokota T, Okada H, Katayama Y, Kunikata T, Kondo M, Nakamura M, Hosono S, et al: Current incidence of clinical kernicterus in preterm infants in Japan. Pediatr Int. 57:494–497. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Radmacher PG, Groves FD, Owa JA, Ofovwe GE, Amuabunos EA, Olusanya BO and Slusher TM: A modified Bilirubin-induced neurologic dysfunction (BIND-M) algorithm is useful in evaluating severity of jaundice in a resource-limited setting. BMC Pediatr. 15:282015. View Article : Google Scholar : PubMed/NCBI | |
|
Morioka I, Iwatani S, Koda T, Iijima K and Nakamura H: Disorders of bilirubin binding to albumin and bilirubin-induced neurologic dysfunction. Semin Fetal Neonatal Med. 20:31–36. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Watchko JF: Kernicterus and the molecular mechanisms of bilirubin-induced CNS injury in newborns. Neuromolecular Med. 8:513–529. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Deganuto M, Cesaratto L, Bellarosa C, Calligaris R, Vilotti S, Renzone G, Foti R, Scaloni A, Gustincich S, Quadrifoglio F, et al: A proteomic approach to the bilirubin-induced toxicity in neuronal cells reveals a protective function of DJ-1 protein. Proteomics. 10:1645–1657. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Brites D: The evolving landscape of neurotoxicity by unconjugated bilirubin: Role of glial cells and inflammation. Front Pharmacol. 3:882012. View Article : Google Scholar : PubMed/NCBI | |
|
Watchko JF and Tiribelli C: Bilirubin-induced neurologic damage - mechanisms and management approaches. N Engl J Med. 369:2021–2030. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Silva SL, Vaz AR, Barateiro A, Falcão AS, Fernandes A, Brito MA, Silva RF and Brites D: Features of bilirubin-induced reactive microglia: From phagocytosis to inflammation. Neurobiol Dis. 40:663–675. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Brites D: Bilirubin injury to neurons and glial cells: New players, novel targets, and newer insights. Semin Perinatol. 35:114–120. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Daood M, Tsai C, Ahdab-Barmada M and Watchko JF: ABC transporter (P-gp/ABCB1, MRP1/ABCC1, BCRP/ABCG2) expression in the developing human CNS. Neuropediatrics. 39:211–218. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Qaisiya M, Brischetto C, Jašprová J, Vitek L, Tiribelli C and Bellarosa C: Bilirubin-induced ER stress contributes to the inflammatory response and apoptosis in neuronal cells. Arch Toxicol. 91:1847–1858. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Chivet M, Javalet C, Laulagnier K, Blot B, Hemming FJ and Sadoul R: Exosomes secreted by cortical neurons upon glutamatergic synapse activation specifically interact with neurons. J Extracell Vesicles. 3:247222014. View Article : Google Scholar : PubMed/NCBI | |
|
Izadpanah M, Seddigh A, Ebrahimi Barough S, Fazeli SAS and Ai J: Potential of extracellular vesicles in neurodegenerative diseases: Diagnostic and therapeutic indications. J Mol Neurosci. 66:172–179. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Paolicelli RC, Bergamini G and Rajendran L: Cell-to-cell communication by extracellular vesicles: Focus on microglia. Neuroscience. 405:148–157. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Xiong XG, Liang Q, Zhang C, Wang Y, Huang W, Peng W, Wang Z and Xia ZA: Serum proteome alterations in patients with cognitive impairment after traumatic brain injury revealed by itraq-based quantitative proteomics. BioMed Res Int. 2017:85725092017. View Article : Google Scholar : PubMed/NCBI | |
|
Núñez Galindo A, Macron C, Cominetti O and Dayon L: Analyzing cerebrospinal fluid proteomes to characterize central nervous system disorders: A highly automated mass spectrometry-based pipeline for biomarker discovery. Methods Mol Biol. 1959:89–112. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Adav SS, Park JE and Sze SK: Quantitative profiling brain proteomes revealed mitochondrial dysfunction in Alzheimer's disease. Mol Brain. 12:82019. View Article : Google Scholar : PubMed/NCBI | |
|
Bortolussi G, Codarin E, Antoniali G, Vascotto C, Vodret S, Arena S, Cesaratto L, Scaloni A, Tell G and Muro AF: Impairment of enzymatic antioxidant defenses is associated with bilirubin-induced neuronal cell death in the cerebellum of Ugt1 KO mice. Cell Death Dis. 6:e17392015. View Article : Google Scholar : PubMed/NCBI | |
|
Chiasserini D, van Weering JRT, Piersma SR, Pham TV, Malekzadeh A, Teunissen CE, de Wit H and Jiménez CR: Proteomic analysis of cerebrospinal fluid extracellular vesicles: A comprehensive dataset. J Proteomics. 106:191–204. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
World Medical Association: World Medical Association Declaration of Helsinki, . Ethical Principles for Medical Research Involving Human Subjects. JAMA. 310:2191–2194. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Bhutani VK and Johnson-Hamerman L: The clinical syndrome of bilirubin-induced neurologic dysfunction. Semin Fetal Neonatal Med. 20:6–13. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Gardiner C, Ferreira YJ, Dragovic RA, Redman CW and Sargent IL: Extracellular vesicle sizing and enumeration by nanoparticle tracking analysis. J Extracell Vesicles. 2:22013. View Article : Google Scholar | |
|
Shao H, Im H, Castro CM, Breakefield X, Weissleder R and Lee H: New technologies for analysis of extracellular vesicles. Chemical reviews. 118:1917–1950. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Taylor DD and Doellgast GJ: Quantitation of peroxidase-antibody binding to membrane fragments using column chromatography. Anal Biochem. 98:53–59. 1979. View Article : Google Scholar : PubMed/NCBI | |
|
Osier N, Motamedi V, Edwards K, Puccio A, Diaz-Arrastia R, Kenney K and Gill J: Exosomes in acquired neurological disorders: New insights into pathophysiology and treatment. Mol Neurobiol. 55:9280–9293. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Tang BL: Promoting axonal regeneration through exosomes: An update of recent findings on exosomal PTEN and mTOR modifiers. Brain Res Bull. 143:123–131. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Fernandes A, Barateiro A, Falcão AS, Silva SL, Vaz AR, Brito MA, Silva RF and Brites D: Astrocyte reactivity to unconjugated bilirubin requires TNF-α and IL-1β receptor signaling pathways. Glia. 59:14–25. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Li M, Song S, Li S, Feng J and Hua Z: The blockade of nf-kappab activation by a specific inhibitory peptide has a strong neuroprotective role in a sprague-dawley rat kernicterus model. J Biol Chem. 290:30042–30052. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Watchko JF: Bilirubin-induced neurotoxicity in the preterm neonate. Clin Perinatol. 43:297–311. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Watchko JF and Maisels MJ: The enigma of low bilirubin kernicterus in premature infants: Why does it still occur, and is it preventable? Semin Perinatol. 38:397–406. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Vodret S, Bortolussi G, Jašprová J, Vitek L and Muro AF: Inflammatory signature of cerebellar neurodegeneration during neonatal hyperbilirubinemia in Ugt1−/− mouse model. J Neuroinflammation. 14:642017. View Article : Google Scholar : PubMed/NCBI | |
|
Kitamura M: Control of NF-κB and inflammation by the unfolded protein response. Int Rev Immunol. 30:4–15. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Feng J, Li M, Wei Q, Li S, Song S and Hua Z: Unconjugated bilirubin induces pyroptosis in cultured rat cortical astrocytes. J Neuroinflammation. 15:232018. View Article : Google Scholar : PubMed/NCBI | |
|
Zhu M, Wang X, Schultzberg M and Hjorth E: Differential regulation of resolution in inflammation induced by amyloid-β42 and lipopolysaccharides in human microglia. J Alzheimers Dis. 43:1237–1250. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Davies MG and Hagen PO: Systemic inflammatory response syndrome. Br J Surg. 84:920–935. 1997. View Article : Google Scholar : PubMed/NCBI | |
|
Anada RP, Wong KT, Jayapalan JJ, Hashim OH and Ganesan D: Panel of serum protein biomarkers to grade the severity of traumatic brain injury. Electrophoresis. 39:2308–2315. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Gasque P, Fontaine M and Morgan BP: Complement expression in human brain. Biosynthesis of terminal pathway components and regulators in human glial cells and cell lines. Immunol. 154:4726–4733. 1995. | |
|
Nataf S, Levison SW and Barnum SR: Expression of the anaphylatoxin C5a receptor in the oligodendrocyte lineage. Brain Res. 894:321–326. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Hammad A, Westacott L and Zaben M: The role of the complement system in traumatic brain injury: A review. J Neuroinflammation. 15:242018. View Article : Google Scholar : PubMed/NCBI | |
|
Brennan FH, Anderson AJ, Taylor SM, Woodruff TM and Ruitenberg MJ: Complement activation in the injured central nervous system: Another dual-edged sword? J Neuroinflammation. 9:1372012. View Article : Google Scholar : PubMed/NCBI | |
|
Bellander BM, Olafsson IH, Ghatan PH, Bro Skejo HP, Hansson LO, Wanecek M and Svensson MA: Secondary insults following traumatic brain injury enhance complement activation in the human brain and release of the tissue damage marker S100B. Acta Neurochir (Wien). 153:90–100. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Stoll BJ, Lee FK, Hale E, Schwartz D, Holmes R, Ashby R, Czerkinsky C and Nahmias AJ: Immunoglobulin secretion by the normal and the infected newborn infant. J Pediatr. 122:780–786. 1993. View Article : Google Scholar : PubMed/NCBI | |
|
Zinn K and Özkan E: Neural immunoglobulin superfamily interaction networks. Curr Opin Neurobiol. 45:99–105. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Denstaedt SJ, Spencer-Segal JL, Newstead MW, Laborc K, Zhao AP, Hjelmaas A, Zeng X, Akil H, Standiford TJ and Singer BH: S100a8/a9 drives neuroinflammatory priming and protects against anxiety-like behavior after sepsis. J Immunol. 200:3188–3200. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Hermani A, De Servi B, Medunjanin S, Tessier PA and Mayer D: S100A8 and S100A9 activate MAP kinase and NF-kappaB signaling pathways and trigger translocation of RAGE in human prostate cancer cells. Exp Cell Res. 312:184–197. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Ghavami S, Rashedi I, Dattilo BM, Eshraghi M, Chazin WJ, Hashemi M, Wesselborg S, Kerkhoff C and Los M: S100A8/A9 at low concentration promotes tumor cell growth via RAGE ligation and MAP kinase-dependent pathway. J Leukoc Biol. 83:1484–1492. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Ryu MJ, Liu Y, Zhong X, Du J, Peterson N, Kong G, Li H, Wang J, Salamat S, Chang Q, et al: Oncogenic Kras expression in postmitotic neurons leads to S100A8-S100A9 protein overexpression and gliosis. J Biol Chem. 287:22948–22958. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Wang S, Song R, Wang Z, Jing Z, Wang S and Ma J: S100A8/A9 in Inflammation. Front Immunol. 9:12982018. View Article : Google Scholar : PubMed/NCBI | |
|
Low D, Subramaniam R, Lin L, Aomatsu T, Mizoguchi A, Ng A, DeGruttola AK, Lee CG, Elias JA, Andoh A, et al: Chitinase 3-like 1 induces survival and proliferation of intestinal epithelial cells during chronic inflammation and colitis-associated cancer by regulating S100A9. Oncotarget. 6:36535–36550. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Donato R, Cannon B, Sorci G, Riuzzi F, Hsu K, Weber D and Geczy C: Functions of s100 proteins. Curr Mol Med. 13:24–57. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Ryckman C, Vandal K, Rouleau P, Talbot M and Tessier PA: Proinflammatory activities of s100: Proteins s100a8, s100a9, and s100a8/a9 induce neutrophil chemotaxis and adhesion. J Immunol. 170:3233–3242. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Pruenster M, Kurz AR, Chung KJ, Cao-Ehlker X, Bieber S, Nussbaum CF, Bierschenk S, Eggersmann TK, Rohwedder I, Heinig K, et al: Extracellular MRP8/14 is a regulator of β2 integrin-dependent neutrophil slow rolling and adhesion. Nat Commun. 6:69152015. View Article : Google Scholar : PubMed/NCBI | |
|
Nishikawa Y, Kajiura Y, Lew JH, Kido JI, Nagata T and Naruishi K: Calprotectin induces il-6 and mcp-1 production via toll-like receptor 4 signaling in human gingival fibroblasts. J Cell Physiol. 232:1862–1871. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Ma L, Sun P, Zhang JC, Zhang Q and Yao SL: Proinflammatory effects of S100A8/A9 via TLR4 and RAGE signaling pathways in BV-2 microglial cells. Int J Mol Med. 40:31–38. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Horvath I, Jia X, Johansson P, Wang C, Moskalenko R, Steinau A, Forsgren L, Wågberg T, Svensson J, Zetterberg H, et al: Pro-inflammatory s100a9 protein as a robust biomarker differentiating early stages of cognitive impairment in alzheimer's disease. ACS Chem Neurosci. 7:34–39. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Wache C, Klein M, Ostergaard C, Angele B, Häcker H, Pfister HW, Pruenster M, Sperandio M, Leanderson T, Roth J, et al: Myeloid-related protein 14 promotes inflammation and injury in meningitis. J Infect Dis. 212:247–257. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Meldolesi J: Exosomes and ectosomes in intercellular communication. Curr Biol. 28:R435–R444. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Fritz G, Botelho HM, Morozova-Roche LA and Gomes CM: Natural and amyloid self-assembly of S100 proteins: Structural basis of functional diversity. FEBS J. 277:4578–4590. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Jansen S, Podschun R, Leib SL, Grötzinger J, Oestern S, Michalek M, Pufe T and Brandenburg LO: Expression and function of psoriasin (S100A7) and koebnerisin (S100A15) in the brain. Infect Immun. 81:1788–1797. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Qin W, Ho L, Wang J, Peskind E and Pasinetti GM: S100A7, a novel Alzheimer's disease biomarker with non-amyloidogenic alpha-secretase activity acts via selective promotion of ADAM-10. PLoS One. 4:e41832009. View Article : Google Scholar : PubMed/NCBI | |
|
Sharma R, Gowda H, Chavan S, Advani J, Kelkar D, Kumar GS, Bhattacharjee M, Chaerkady R, Prasad TS, Pandey A, et al: Proteomic signature of endothelial dysfunction identified in the serum of acute ischemic stroke patients by the itraq-based lc-ms approach. J Proteome Res. 14:2466–2479. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Kim C and Kaufmann SH: Defensin: A multifunctional molecule lives up to its versatile name. Trends Microbiol. 14:428–431. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Park YG, Jeong JK, Lee JH, Lee YJ, Seol JW, Kim SJ, Hur TY, Jung YH, Kang SJ and Park SY: Lactoferrin protects against prion protein-induced cell death in neuronal cells by preventing mitochondrial dysfunction. Int J Mol Med. 31:325–330. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Semple F and Dorin JR: β-Defensins: Multifunctional modulators of infection, inflammation and more? J Innate Immun. 4:337–348. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Tollner TL, Bevins CL and Cherr GN: Multifunctional glycoprotein DEFB126 - a curious story of defensin-clad spermatozoa. Nat Rev Urol. 9:365–375. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Kazakos EI, Kountouras J, Polyzos SA and Deretzi G: Novel aspects of defensins' involvement in virus-induced autoimmunity in the central nervous system. Med Hypotheses. 102:33–36. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Williams WM, Torres S, Siedlak SL, Castellani RJ, Perry G, Smith MA and Zhu X: Antimicrobial peptide β-defensin-1 expression is upregulated in Alzheimer's brain. J Neuroinflammation. 10:1272013. View Article : Google Scholar : PubMed/NCBI | |
|
Rocha-Ferreira E and Hristova M: Antimicrobial peptides and complement in neonatal hypoxia-ischemia induced brain damage. Front Immunol. 6:562015. View Article : Google Scholar : PubMed/NCBI | |
|
Miles K, Clarke DJ, Lu W, Sibinska Z, Beaumont PE, Davidson DJ, Barr TA, Campopiano DJ and Gray M: Dying and necrotic neutrophils are anti-inflammatory secondary to the release of alpha-defensins. J Immunol. 183:2122–2132. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Zakharova ET, Sokolov AV, Pavlichenko NN, Kostevich VA, Abdurasulova IN, Chechushkov AV, Voynova IV, Elizarova AY, Kolmakov NN, Bass MG, et al: Erythropoietin and Nrf2: Key factors in the neuroprotection provided by apo-lactoferrin. Biometals. 31:425–443. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Legrand D, Elass E, Carpentier M and Mazurier J: Lactoferrin: A modulator of immune and inflammatory responses. Cell Mol Life Sci. 62:2549–2559. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Legrand D: Lactoferrin, a key molecule in immune and inflammatory processes. Biochem Cell Biol. 90:252–268. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Bennett RM and Kokocinski T: Lactoferrin content of peripheral blood cells. Br J Haematol. 39:509–521. 1978. View Article : Google Scholar : PubMed/NCBI | |
|
Qaisiya M, Coda Zabetta CD, Bellarosa C and Tiribelli C: Bilirubin mediated oxidative stress involves antioxidant response activation via Nrf2 pathway. Cell Signal. 26:512–520. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Ginet V, van de Looij Y, Petrenko V, Toulotte A, Kiss J, Hüppi PS and Sizonenko SV: Lactoferrin during lactation reduces lipopolysaccharide-induced brain injury. Biofactors. 42:323–336. 2016.PubMed/NCBI | |
|
van de Looij Y, Ginet V, Chatagner A, Toulotte A, Somm E, Hüppi PS and Sizonenko SV: Lactoferrin during lactation protects the immature hypoxic-ischemic rat brain. Ann Clin Transl Neurol. 1:955–967. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Somm E, Larvaron P, van de Looij Y, Toulotte A, Chatagner A, Faure M, Métairon S, Mansourian R, Raymond F, Gruetter R, et al: Protective effects of maternal nutritional supplementation with lactoferrin on growth and brain metabolism. Pediatr Res. 75:51–61. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Lee SH, Pyo CW, Hahm DH, Kim J and Choi SY: Iron-saturated lactoferrin stimulates cell cycle progression through PI3K/Akt pathway. Mol Cells. 28:37–42. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Thompson AG, Gray E, Heman-Ackah SM, Mäger I, Talbot K, Andaloussi SE, Wood MJ and Turner MR: Extracellular vesicles in neurodegenerative disease - pathogenesis to biomarkers. Nat Rev Neurol. 12:346–357. 2016. View Article : Google Scholar : PubMed/NCBI |
