Neuregulin-1 attenuates mortality associated with experimental cerebral malaria

Journal of Neuroinflammation

Volumn 11, Issue , 2014, Pages

  Solomon, Wesley ^a   Wilson, Nana O ^a   Anderson, Leonard ^a   Pitts, Sidney ^a   Patrickson, John ^a   Liu, Mingli ^a   Ford, Byron D ^a   Stiles, Jonathan K ^a  

^a MOREHOUSE SCHOOL OF MEDICINE   (United States)

Author keywords

Adjunctive therapy; Anti inflammatory; Blood brain barrier (BBB); Brain injury; Cerebral malaria (CM); Inflammation; Malaria; Neuregulin 1 (NRG 1); Plasmodium berghei ANKA (PbA); Pro inflammatory

Indexed keywords

ARTEMETHER; NEU DIFFERENTIATION FACTOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIINFLAMMATORY ACTIVITY; ANTIPROTOZOAL ACTIVITY; ARTICLE; BRAIN INJURY; BRAIN MALARIA; CONTROLLED STUDY; DISEASE ASSOCIATION; DRUG EFFICACY; EXPERIMENTAL INFECTION; EXTRACELLULAR MATRIX; INFECTION PREVENTION; MORTALITY; MOUSE; NEUROPATHOLOGY; NEUROPROTECTION; NONHUMAN; PARASITE CLEARANCE; PLASMODIUM BERGHEI; PLASMODIUM BERGHEI INFECTION; SURVIVAL;

ANIMALS; ANTIMALARIALS; ARTEMISININS; BEHAVIOR, ANIMAL; BLOOD-BRAIN BARRIER; BRAIN; CYTOKINES; DISEASE MODELS, ANIMAL; ENCEPHALITIS; ENDOTHELIUM; LEUKOCYTES; MALARIA, CEREBRAL; MICE; MICE, INBRED C57BL; NEUREGULIN-1; NEUROPROTECTIVE AGENTS; PLASMODIUM BERGHEI;

EID: 84892471542     PISSN: None     EISSN: 17422094     Source Type: Journal    
DOI: 10.1186/1742-2094-11-9     Document Type: Article

References (136)

1. World Health Organization World Malaria Report 2011. http://www.who.int/malaria/world_malaria_report_2011/WMR2011_noprofiles_lowres.pdf, World Health Organization.
2. Bondi FS. The incidence and outcome of neurological abnormalities in childhood cerebral malaria: a long-term follow-up of 62 survivors. Trans R Soc Trop Med Hyg 1992, 86:17-19. 10.1016/0035-9203(92)90420-H, 1566292.
3. Brewster DR, Kwiatkowski D, White NJ. Neurological sequelae of cerebral malaria in children. Lancet 1990, 336:1039-1043. 10.1016/0140-6736(90)92498-7, 1977027.
4. Holding PA, Stevenson J, Peshu N, Marsh K. Cognitive sequelae of severe malaria with impaired consciousness. Trans R Soc Trop Med Hyg 1999, 93:529-534. 10.1016/S0035-9203(99)90368-1, 10696414.
5. Idro R, Kakooza-Mwesige A, Balyejjussa S, Mirembe G, Mugasha C, Tugumisirize J, Byarugaba J. Severe neurological sequelae and behaviour problems after cerebral malaria in Ugandan children. BMC Res Notes 2010, 3:104. 10.1186/1756-0500-3-104, 2861066, 20398391.
6. Boivin MJ, Bangirana P, Byarugaba J, Opoka RO, Idro R, Jurek AM, John CC. Cognitive impairment after cerebral malaria in children: a prospective study. Pediatrics 2007, 119:e360-e366. 10.1542/peds.2006-2027, 2743741, 17224457.
7. Murphy SC, Breman JG. Gaps in the childhood malaria burden in Africa: cerebral malaria, neurological sequelae, anemia, respiratory distress, hypoglycemia, and complications of pregnancy. Am J Trop Med Hyg 2001, 64(Suppl 1-2):57-67.
8. Meremikwu MM, Asindi AA, Ezedinachi E. The pattern of neurological sequelae of childhood cerebral malaria among survivors in Calabar, Nigeria. Cent Afr J Med 1997, 43:231-234.
9. Idro R, Marsh K, John CC, Newton CR. Cerebral malaria: mechanisms of brain injury and strategies for improved neurocognitive outcome. Pediatr Res 2010, 68:267-274. 3056312, 20606600.
10. Newton CR, Krishna S. Severe falciparum malaria in children: current understanding of pathophysiology and supportive treatment. Pharmacol Ther 1998, 79:1-53. 10.1016/S0163-7258(98)00008-4, 9719344.
11. Dondorp A, Nosten F, Stepniewska K, Day N, White N. Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial. Lancet 2005, 366:717-725.
12. Mishra SK, Wiese L. Advances in the management of cerebral malaria in adults. Curr Opin Neurol 2009, 22:302-307. 10.1097/WCO.0b013e32832a323d, 19434799.
13. Mohanty S, Patel DK, Pati SS, Mishra SK. Adjuvant therapy in cerebral malaria. Indian J Med Res 2006, 124:245-260.
14. John CC, Kutamba E, Mugarura K, Opoka RO. Adjunctive therapy for cerebral malaria and other severe forms of Plasmodium falciparum malaria. Expert Rev Anti Infect Ther 2010, 8:997-1008. 10.1586/eri.10.90, 2987235, 20818944.
15. Day NP, Hien TT, Schollaardt T, Loc PP, Chuong LV, Chau TT, Mai NT, Phu NH, Sinh DX, White NJ, Ho M. The prognostic and pathophysiologic role of pro- and antiinflammatory cytokines in severe malaria. J Infect Dis 1999, 180:1288-1297. 10.1086/315016, 10479160.
16. Brown H, Turner G, Rogerson S, Tembo M, Mwenechanya J, Molyneux M, Taylor T. Cytokine expression in the brain in human cerebral malaria. J Infect Dis 1999, 180:1742-1746. 10.1086/315078, 10515846.
17. Hansen DS. Inflammatory responses associated with the induction of cerebral malaria: lessons from experimental murine models. PLoS Pathog 2012, 8:e1003045. 10.1371/journal.ppat.1003045, 3531491, 23300435.
18. Nacer A, Movila A, Baer K, Mikolajczak SA, Kappe SH, Frevert U. Neuroimmunological blood brain barrier opening in experimental cerebral malaria. PLoS Pathog 2012, 8:e1002982. 10.1371/journal.ppat.1002982, 3486917, 23133375.
19. Hunt NH, Grau GE. Cytokines: accelerators and brakes in the pathogenesis of cerebral malaria. Trends Immunol 2003, 24:491-499. 10.1016/S1471-4906(03)00229-1, 12967673.
20. John CC, Panoskaltsis-Mortari A, Opoka RO, Park GS, Orchard PJ, Jurek AM, Idro R, Byarugaba J, Boivin MJ. Cerebrospinal fluid cytokine levels and cognitive impairment in cerebral malaria. Am J Trop Med Hyg 2008, 78:198-205. 2254318, 18256412.
21. Schofield L, Grau GE. Immunological processes in malaria pathogenesis. Nat Rev Immunol 2005, 5:722-735. 10.1038/nri1686, 16138104.
22. Verra F, Mangano VD, Modiano D. Genetics of susceptibility to Plasmodium falciparum: from classical malaria resistance genes towards genome-wide association studies. Parasite Immunol 2009, 31:234-253. 10.1111/j.1365-3024.2009.01106.x, 19388945.
23. Driss A, Hibbert JM, Wilson NO, Iqbal SA, Adamkiewicz TV, Stiles JK. Genetic polymorphisms linked to susceptibility to malaria. Malar J 2011, 10:271. 3184115, 21929748.
24. Hill AV. The immunogenetics of resistance to malaria. Proc Assoc Am Physicians 1999, 111:272-277. 10.1046/j.1525-1381.1999.99234.x, 10417733.
25. Taoufiq Z, Pino P, N'Dilimabaka N, Arrouss I, Assi S, Soubrier F, Rebollo A, Mazier D. Atorvastatin prevents Plasmodium falciparum cytoadherence and endothelial damage. Malar J 2011, 10:52. 3056843, 21356073.
26. Wilson NO, Solomon W, Anderson L, Patrickson J, Pitts S, Bond V, Liu M, Stiles JK. Pharmacologic inhibition of CXCL10 in combination with anti-malarial therapy eliminates mortality associated with murine model of cerebral malaria. PLoS One 2013, 8:e60898. 10.1371/journal.pone.0060898, 3618178, 23630573.
27. Achtman AH, Pilat S, Law CW, Lynn DJ, Janot L, Mayer ML, Ma S, Kindrachuk J, Finlay BB, Brinkman FS, Smyth GK, Hancock RE, Schofield L. Effective adjunctive therapy by an innate defense regulatory peptide in a preclinical model of severe malaria. Sci Transl Med 2012, 4:135-164.
28. Li Y, Tennekoon GI, Birnbaum M, Marchionni MA, Rutkowski JL. Neuregulin signaling through a PI3K/Akt/Bad pathway in Schwann cell survival. Mol Cell Neurosci 2001, 17:761-767. 10.1006/mcne.2000.0967, 11312610.
29. Falls DL. Neuregulins: functions, forms, and signaling strategies. Exp Cell Res 2003, 284:14-30. 10.1016/S0014-4827(02)00102-7, 12648463.
30. Talmage DA. Mechanisms of neuregulin action. Novartis Found Symp 2008, 289:74-84. discussion 84-93, 2621364, 18497096.
31. Buonanno A, Fischbach GD. Neuregulin and ErbB receptor signaling pathways in the nervous system. Curr Opin Neurobiol 2001, 11:287-296. 10.1016/S0959-4388(00)00210-5, 11399426.
32. Xu Z, Ford GD, Croslan DR, Jiang J, Gates A, Allen R, Ford BD. Neuroprotection by neuregulin-1 following focal stroke is associated with the attenuation of ischemia-induced pro-inflammatory and stress gene expression. Neurobiol Dis 2005, 19:461-470. 10.1016/j.nbd.2005.01.027, 16023588.
33. Xu Z, Jiang J, Ford G, Ford BD. Neuregulin-1 is neuroprotective and attenuates inflammatory responses induced by ischemic stroke. Biochem Biophys Res Commun 2004, 322:440-446. 10.1016/j.bbrc.2004.07.149, 15325249.
34. Li Y, Xu Z, Ford GD, Croslan DR, Cairobe T, Li Z, Ford BD. Neuroprotection by neuregulin-1 in a rat model of permanent focal cerebral ischemia. Brain Res 2007, 1184:277-283. 2374743, 17961519.
35. Li Y, Lein PJ, Liu C, Bruun DA, Giulivi C, Ford GD, Tewolde T, Ross-Inta C, Ford BD. Neuregulin-1 is neuroprotective in a rat model of organophosphate-induced delayed neuronal injury. Toxicol Appl Pharmacol 2012, 262:194-204. 10.1016/j.taap.2012.05.001, 3607352, 22583949.
36. Xu Z, Croslan DR, Harris AE, Ford GD, Ford BD. Extended therapeutic window and functional recovery after intraarterial administration of neuregulin-1 after focal ischemic stroke. J Cereb Blood Flow Metab 2006, 26:527-535. 10.1038/sj.jcbfm.9600212, 16136057.
37. Lok J, Zhao S, Leung W, Seo JH, Navaratna D, Wang X, Whalen MJ, Lo EH. Neuregulin-1 effects on endothelial and blood-brain-barrier permeability after experimental injury. Transl Stroke Res 2012, 3:S119-S124. 10.1007/s12975-012-0157-x, 3389802, 22773936.
38. Stanimirovic D, Satoh K. Inflammatory mediators of cerebral endothelium: a role in ischemic brain inflammation. Brain Pathol 2000, 10:113-126.
39. Kim JS, Chopp M, Chen H, Levine SR, Carey JL, Welch KM. Adhesive glycoproteins CD11a and CD18 are upregulated in the leukocytes from patients with ischemic stroke and transient ischemic attacks. J Neurol Sci 1995, 128:45-50. 10.1016/0022-510X(94)00203-Z, 7722533.
40. Stoll G, Jander S, Schroeter M. Inflammation and glial responses in ischemic brain lesions. Prog Neurobiol 1998, 56:149-171. 10.1016/S0301-0082(98)00034-3, 9760699.
41. Clemmer L, Martins YC, Zanini GM, Frangos JA, Carvalho LJ. Artemether and artesunate show the highest efficacies in rescuing mice with late-stage cerebral malaria and rapidly decrease leukocyte accumulation in the brain. Antimicrob Agents Chemother 2011, 55:1383-1390. 10.1128/AAC.01277-10, 3067152, 21220531.
42. Lackner P, Beer R, Heussler V, Goebel G, Rudzki D, Helbok R, Tannich E, Schmutzhard E. Behavioural and histopathological alterations in mice with cerebral malaria. Neuropathol Appl Neurobiol 2006, 32:177-188. 10.1111/j.1365-2990.2006.00706.x, 16599946.
43. Martins YC, Werneck GL, Carvalho LJ, Silva BP, Andrade BG, Souza TM, Souza DO, Daniel-Ribeiro CT. Algorithms to predict cerebral malaria in murine models using the SHIRPA protocol. Malar J 2010, 9:85. 2850361, 20334682.
44. Waknine-Grinberg JH, Hunt N, Bentura-Marciano A, McQuillan JA, Chan HW, Chan WC, Barenholz Y, Haynes RK, Golenser J. Artemisone effective against murine cerebral malaria. Malar J 2010, 9:227. 2928250, 20691118.
45. Belnoue E, Kayibanda M, Vigario AM, Deschemin JC, Van Rooijen N, Viguier M, Snounou G, Renia L. On the pathogenic role of brain-sequestered alphabeta CD8+ T cells in experimental cerebral malaria. J Immunol 2002, 169:6369-6375.
46. Faille D, El-Assaad F, Alessi MC, Fusai T, Combes V, Grau GE. Platelet-endothelial cell interactions in cerebral malaria: the end of a cordial understanding. Thromb Haemost 2009, 102:1093-1102.
47. Favre N, Da Laperousaz C, Ryffel B, Weiss NA, Imhof BA, Rudin W, Lucas R, Piguet PF. Role of ICAM-1 (CD54) in the development of murine cerebral malaria. Microbes Infect 1999, 1:961-968. 10.1016/S1286-4579(99)80513-9, 10617927.
48. Fiedler U, Augustin HG. Angiopoietins: a link between angiogenesis and inflammation. Trends Immunol 2006, 27(12):552-558. 10.1016/j.it.2006.10.004, 17045842.
49. Fiedler U, Reiss Y, Scharpfenecker M, Grunow V, Koidl S, Thurston G, Gale NW, Witzenrath M, Rosseau S, Suttorp N, Sobke A, Herrmann M, Preissner KT, Vajkoczy P, Augustin HG. Angiopoietin-2 sensitizes endothelial cells to TNF-alpha and has a crucial role in the induction of inflammation. Nat Med 2006, 12:235-239. 10.1038/nm1351, 16462802.
50. Nag S, Papneja T, Venugopalan R, Stewart DJ. Increased angiopoietin2 expression is associated with endothelial apoptosis and blood-brain barrier breakdown. Lab Invest 2005, 85(10):1189-1198. 10.1038/labinvest.3700325, 16056241.
51. Pino P, Taoufiq Z, Nitcheu J, Vouldoukis I, Mazier D. Blood-brain barrier breakdown during cerebral malaria: suicide or murder?. Thromb Haemost 2005, 94(2):336-340.
52. Conroy AL, Lafferty EI, Lovegrove FE, Krudsood S, Tangpukdee N, Liles WC, Kain KC. Whole blood angiopoietin-1 and -2 levels discriminate cerebral and severe (non-cerebral) malaria from uncomplicated malaria. Malar J 2009, 8:295. 2806378, 20003529.
53. Lovegrove FE, Tangpukdee N, Opoka RO, Lafferty EI, Rajwans N, Hawkes M, Krudsood S, Looareesuwan S, John CC, Liles WC, Kain KC. Serum angiopoietin-1 and -2 levels discriminate cerebral malaria from uncomplicated malaria and predict clinical outcome in African children. PLoS One 2009, 4:e4912. 10.1371/journal.pone.0004912, 2657207, 19300530.
54. Jain V, Lucchi NW, Wilson NO, Blackstock AJ, Nagpal AC, Joel PK, Singh MP, Udhayakumar V, Stiles JK, Singh N. Plasma levels of angiopoietin-1 and -2 predict cerebral malaria outcome in Central India. Malar J 2011, 10:383. 3286486, 22192385.
55. Alam T, An MR, Papaconstantinou J. Differential expression of three C/EBP isoforms in multiple tissues during the acute phase response. J Biol Chem 1992, 267:5021-5024.
56. Baumann H, Morella KK, Campos SP, Cao Z, Jahreis GP. Role of CAAT-enhancer binding protein isoforms in the cytokine regulation of acute-phase plasma protein genes. J Biol Chem 1992, 267:19744-19751.
57. Poli V. The role of C/EBP isoforms in the control of inflammatory and native immunity functions. J Biol Chem 1998, 273:29279-29282. 10.1074/jbc.273.45.29279, 9792624.
58. Fields J, Ghorpade A. C/EBPbeta regulates multiple IL-1beta-induced human astrocyte inflammatory genes. J Neuroinflammation 2012, 9:177. 10.1186/1742-2094-9-177, 3464795, 22818222.
59. Natsuka S, Akira S, Nishio Y, Hashimoto S, Sugita T, Isshiki H, Kishimoto T. Macrophage differentiation-specific expression of NF-IL6, a transcription factor for interleukin-6. Blood 1992, 79:460-466.
60. Kovacs KA, Steinmann M, Magistretti PJ, Halfon O, Cardinaux JR. C/EBPbeta couples dopamine signalling to substance P precursor gene expression in striatal neurones. J Neurochem 2006, 98:1390-1399. 10.1111/j.1471-4159.2006.03957.x, 16771829.
61. Greenwel P, Tanaka S, Penkov D, Zhang W, Olive M, Moll J, Vinson C, Di Liberto M, Ramirez F. Tumor necrosis factor alpha inhibits type I collagen synthesis through repressive CCAAT/enhancer-binding proteins. Mol Cell Biol 2000, 20:912-918. 10.1128/MCB.20.3.912-918.2000, 85208, 10629048.
62. Maggi CA. The effects of tachykinins on inflammatory and immune cells. Regul Pept 1997, 70:75-90. 10.1016/S0167-0115(97)00029-3, 9272619.
63. Armah H, Wired EK, Dodoo AK, Adjei AA, Tettey Y, Gyasi R. Cytokines and adhesion molecules expression in the brain in human cerebral malaria. Int J Environ Res Public Health 2005, 2:123-131. 10.3390/ijerph2005010123, 3814706, 16705810.
64. Turner GD, Morrison H, Jones M, Davis TM, Looareesuwan S, Buley ID, Gatter KC, Newbold CI, Pukritayakamee S, Nagachinta B, White NJ, Berendt AR. An immunohistochemical study of the pathology of fatal malaria. Evidence for widespread endothelial activation and a potential role for intercellular adhesion molecule-1 in cerebral sequestration. Am J Pathol 1994, 145:1057-1069. 1887431, 7526692.
65. De Kossodo S, Grau GE. Role of cytokines and adhesion molecules in malaria immunopathology. Stem Cells 1993, 11:41-48. 10.1002/stem.5530110108, 8457780.
66. De Vries HE, Blom-Roosemalen MC, Van Oosten M, De Boer AG, Van Berkel TJ, Breimer DD, Kuiper J. The influence of cytokines on the integrity of the blood-brain barrier in vitro. J Neuroimmunol 1996, 64:37-43. 10.1016/0165-5728(95)00148-4, 8598388.
67. Jakobsen PH, McKay V, Morris-Jones SD, McGuire W, Van Hensbroek MB, Meisner S, Bendtzen K, Schousboe I, Bygbjerg IC, Greenwood BM. Increased concentrations of interleukin-6 and interleukin-1 receptor antagonist and decreased concentrations of beta-2-glycoprotein I in Gambian children with cerebral malaria. Infect Immun 1994, 62:4374-4379. 303119, 7927698.
68. Kwiatkowski D, Hill AV, Sambou I, Twumasi P, Castracane J, Manogue KR, Cerami A, Brewster DR, Greenwood BM. TNF concentration in fatal cerebral, non-fatal cerebral, and uncomplicated Plasmodium falciparum malaria. Lancet 1990, 336:1201-1204. 10.1016/0140-6736(90)92827-5, 1978068.
69. Lyke KE, Burges R, Cissoko Y, Sangare L, Dao M, Diarra I, Kone A, Harley R, Plowe CV, Doumbo OK, Sztein MB. Serum levels of the proinflammatory cytokines interleukin-1 beta (IL-1beta), IL-6, IL-8, IL-10, tumor necrosis factor alpha, and IL-12(p70) in Malian children with severe Plasmodium falciparum malaria and matched uncomplicated malaria or healthy controls. Infect Immun 2004, 72:5630-5637. 10.1128/IAI.72.10.5630-5637.2004, 517593, 15385460.
70. Netea MG, Kullberg BJ, Van der Meer JW. Circulating cytokines as mediators of fever. Clin Infect Dis 2000, 31(Suppl 5):S178-S184.
71. Thornton P, McColl BW, Greenhalgh A, Denes A, Allan SM, Rothwell NJ. Platelet interleukin-1alpha drives cerebrovascular inflammation. Blood 2010, 115:3632-3639. 10.1182/blood-2009-11-252643, 20200351.
72. Armah HB, Wilson NO, Sarfo BY, Powell MD, Bond VC, Anderson W, Adjei AA, Gyasi RK, Tettey Y, Wiredu EK, Tongren JE, Udhayakumar V, Stiles JK. Cerebrospinal fluid and serum biomarkers of cerebral malaria mortality in Ghanaian children. Malar J 2007, 6:147. 2186349, 17997848.
73. Jain V, Armah HB, Tongren JE, Ned RM, Wilson NO, Crawford S, Joel PK, Singh MP, Nagpal AC, Dash AP, Udhayakumar V, Singh N, Stiles JK. Plasma IP-10, apoptotic and angiogenic factors associated with fatal cerebral malaria in India. Malar J 2008, 7:83. 2405803, 18489763.
74. Wilson NO, Jain V, Roberts CE, Lucchi N, Joel PK, Singh MP, Nagpal AC, Dash AP, Udhayakumar V, Singh N, Stiles JK. CXCL4 and CXCL10 predict risk of fatal cerebral malaria. Dis Markers 2011, 30:39-49. 10.1155/2011/828256, 3260027,3260027, 21508508.
75. Campanella GS, Tager AM, El Khoury JK, Thomas SY, Abrazinski TA, Manice LA, Colvin RA, Luster AD. Chemokine receptor CXCR3 and its ligands CXCL9 and CXCL10 are required for the development of murine cerebral malaria. Proc Natl Acad Sci USA 2008, 105:4814-4819. 10.1073/pnas.0801544105, 2290783, 18347328.
76. Manjurano A, Clark TG, Nadjm B, Mtove G, Wangai H, Sepulveda N, Campino SG, Maxwell C, Olomi R, Rockett KR, Jeffreys A, Riley EM, Reyburn H, Drakeley C, MalariaGen Consortium Candidate human genetic polymorphisms and severe malaria in a Tanzanian population. PLoS One 2012, 7:e47463. 10.1371/journal.pone.0047463, 3483265, 23144702, MalariaGen Consortium.
77. Naka I, Nishida N, Patarapotikul J, Nuchnoi P, Tokunaga K, Hananantachai H, Tsuchiya N, Ohashi J. Identification of a haplotype block in the 5q31 cytokine gene cluster associated with the susceptibility to severe malaria. Malar J 2009, 8:232. 2770543, 19840389.
78. Ohashi J, Naka I, Patarapotikul J, Hananantachai H, Looareesuwan S, Tokunaga K. A single-nucleotide substitution from C to T at position -1055 in the IL-13 promoter is associated with protection from severe malaria in Thailand. Genes Immun 2003, 4:528-531. 10.1038/sj.gene.6364010, 14551608.
79. Prakash D, Fesel C, Jain R, Cazenave PA, Mishra GC, Pied S. Clusters of cytokines determine malaria severity in Plasmodium falciparum-infected patients from endemic areas of Central India. J Infect Dis 2006, 194:198-207. 10.1086/504720, 16779726.
80. John CC, Park GS, Sam-Agudu N, Opoka RO, Boivin MJ. Elevated serum levels of IL-1ra in children with Plasmodium falciparum malaria are associated with increased severity of disease. Cytokine 2008, 41:204-208. 10.1016/j.cyto.2007.12.008, 2323512, 18282763.
81. Pasvol G. The treatment of complicated and severe malaria. Br Med Bull 2005, 75-76:29-47.
82. World Health Organization Guidelines for the treatment of malaria, second edition. http://whqlibdoc.who.int/publications/2010/9789241547925_eng.pdf, World Health Organization.
83. Aikawa M, Iseki M, Barnwell JW, Taylor D, Oo MM, Howard RJ. The pathology of human cerebral malaria. Am J Trop Med Hyg 1990, 43(2 Pt 2):30-37.
84. Angulo I, Fresno M. Cytokines in the pathogenesis of and protection against malaria. Clin Diagn Lab Immunol 2002, 9:1145-1152. 130117, 12414742.
85. Idro R, Jenkins NE, Newton CR. Pathogenesis, clinical features, and neurological outcome of cerebral malaria. Lancet Neurol 2005, 4:827-840. 10.1016/S1474-4422(05)70247-7, 16297841.
86. Hearn J, Rayment N, Landon DN, Katz DR, De Souza JB. Immunopathology of cerebral malaria: morphological evidence of parasite sequestration in murine brain microvasculature. Infect Immun 2000, 68:5364-5376. 10.1128/IAI.68.9.5364-5376.2000, 101800, 10948166.
87. Baptista FG, Pamplona A, Pena AC, Mota MM, Pied S, Vigario AM. Accumulation of Plasmodium berghei-infected red blood cells in the brain is crucial for the development of cerebral malaria in mice. Infect Immun 2010, 78:4033-4039. 10.1128/IAI.00079-10, 2937458, 20605973.
88. Castell JV, Gomez-Lechon MJ, David M, Andus T, Geiger T, Trullenque R, Fabra R, Heinrich PC. Interleukin-6 is the major regulator of acute phase protein synthesis in adult human hepatocytes. FEBS Lett 1989, 242:237-239. 10.1016/0014-5793(89)80476-4, 2464504.
89. Heinrich PC, Castell JV, Andus T. Interleukin-6 and the acute phase response. Biochem J 1990, 265:621-636. 1133681, 1689567.
90. Campbell IL, Abraham CR, Masliah E, Kemper P, Inglis JD, Oldstone MB, Mucke L. Neurologic disease induced in transgenic mice by cerebral overexpression of interleukin 6. Proc Natl Acad Sci USA 1993, 90:10061-10065. 10.1073/pnas.90.21.10061, 47713, 7694279.
91. Issekutz AC, Issekutz TB. Quantitation and kinetics of blood monocyte migration to acute inflammatory reactions, and IL-1 alpha, tumor necrosis factor-alpha, and IFN-gamma. J Immunol 1993, 151:2105-2115.
92. Issekutz AC, Lopes N, Issekutz TB. Role of interleukin-1 and tumour necrosis factor in leukocyte recruitment to acute dermal inflammation. Mediators Inflamm 1992, 1:347-353. 10.1155/S0962935192000528, 2365361, 18475483.
93. Miu J, Mitchell AJ, Muller M, Carter SL, Manders PM, McQuillan JA, Saunders BM, Ball HJ, Lu B, Campbell IL, Hunt NH. Chemokine gene expression during fatal murine cerebral malaria and protection due to CXCR3 deficiency. J Immunol 2008, 180:1217-1230.
94. Minhas N, Xue M, Fukudome K, Jackson CJ. Activated protein C utilizes the angiopoietin/Tie2 axis to promote endothelial barrier function. Faseb J 2010, 24:873-881. 10.1096/fj.09-134445, 19858095.
95. Fagiani E, Christofori G. Angiopoietins in angiogenesis. Cancer Lett 2013, 328:18-26. 10.1016/j.canlet.2012.08.018, 22922303.
96. Tsigkos S, Koutsilieris M, Papapetropoulos A. Angiopoietins in angiogenesis and beyond. Expert Opin Investig Drugs 2003, 12:933-941. 10.1517/13543784.12.6.933, 12783598.
97. Jeansson M, Gawlik A, Anderson G, Li C, Kerjaschki D, Henkelman M, Quaggin SE. Angiopoietin-1 is essential in mouse vasculature during development and in response to injury. J Clin Invest 2011, 121:2278-2289. 10.1172/JCI46322, 3104773, 21606590.
98. Gamble JR, Drew J, Trezise L, Underwood A, Parsons M, Kasminkas L, Rudge J, Yancopoulos G, Vadas MA. Angiopoietin-1 is an antipermeability and anti-inflammatory agent in vitro and targets cell junctions. Circ Res 2000, 87:603-607. 10.1161/01.RES.87.7.603, 11009566.
99. Gavard J, Patel V, Gutkind JS. Angiopoietin-1 prevents VEGF-induced endothelial permeability by sequestering Src through mDia. Dev Cell 2008, 14:25-36. 10.1016/j.devcel.2007.10.019, 18194650.
100. Pizurki L, Zhou Z, Glynos K, Roussos C, Papapetropoulos A. Angiopoietin-1 inhibits endothelial permeability, neutrophil adherence and IL-8 production. Br J Pharmacol 2003, 139:329-336. 10.1038/sj.bjp.0705259, 1573855, 12770938.
101. Jho D, Mehta D, Ahmmed G, Gao XP, Tiruppathi C, Broman M, Malik AB. Angiopoietin-1 opposes VEGF-induced increase in endothelial permeability by inhibiting TRPC1-dependent Ca2 influx. Circ Res 2005, 96:1282-1290. 10.1161/01.RES.0000171894.03801.03, 15920022.
102. Jones N, Iljin K, Dumont DJ, Alitalo K. Tie receptors: new modulators of angiogenic and lymphangiogenic responses. Nat Rev Mol Cell Biol 2001, 2:257-267. 10.1038/35067005, 11283723.
103. Suri C, Jones PF, Patan S, Bartunkova S, Maisonpierre PC, Davis S, Sato TN, Yancopoulos GD. Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell 1996, 87:1171-1180. 10.1016/S0092-8674(00)81813-9, 8980224.
104. Thurston G, Rudge JS, Ioffe E, Zhou H, Ross L, Croll SD, Glazer N, Holash J, McDonald DM, Yancopoulos GD. Angiopoietin-1 protects the adult vasculature against plasma leakage. Nat Med 2000, 6:460-463. 10.1038/74725, 10742156.
105. Uemura A, Ogawa M, Hirashima M, Fujiwara T, Koyama S, Takagi H, Honda Y, Wiegand SJ, Yancopoulos GD, Nishikawa S. Recombinant angiopoietin-1 restores higher-order architecture of growing blood vessels in mice in the absence of mural cells. J Clin Invest 2002, 110:1619-1628. 151628, 12464667.
106. Kim I, Moon SO, Park SK, Chae SW, Koh GY. Angiopoietin-1 reduces VEGF-stimulated leukocyte adhesion to endothelial cells by reducing ICAM-1, VCAM-1, and E-selectin expression. Circ Res 2001, 89:477-479. 10.1161/hh1801.097034, 11557733.
107. Mandriota SJ, Pepper MS. Regulation of angiopoietin-2 mRNA levels in bovine microvascular endothelial cells by cytokines and hypoxia. Circ Res 1998, 83:852-859. 10.1161/01.RES.83.8.852, 9776732.
108. Roviezzo F, Tsigkos S, Kotanidou A, Bucci M, Brancaleone V, Cirino G, Papapetropoulos A. Angiopoietin-2 causes inflammation in vivo by promoting vascular leakage. J Pharmacol Exp Ther 2005, 314:738-744. 10.1124/jpet.105.086553, 15870388.
109. Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, Compton D, McClain J, Aldrich TH, Papadopoulos N, Daly TJ, Davis S, Sato TN, Yancopoulos GD. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 1997, 277:55-60. 10.1126/science.277.5322.55, 9204896.
110. Lobov IB, Brooks PC, Lang RA. Angiopoietin-2 displays VEGF-dependent modulation of capillary structure and endothelial cell survival in vivo. Proc Natl Acad Sci USA 2002, 99:11205-11210. 10.1073/pnas.172161899, 123234, 12163646.
111. Cao Y, Sonveaux P, Liu S, Zhao Y, Mi J, Clary BM, Li CY, Kontos CD, Dewhirst MW. Systemic overexpression of angiopoietin-2 promotes tumor microvessel regression and inhibits angiogenesis and tumor growth. Cancer Res 2007, 67:3835-3844. 10.1158/0008-5472.CAN-06-4056, 17440098.
112. Mandriota SJ, Pyke C, Di Sanza C, Quinodoz P, Pittet B, Pepper MS. Hypoxia-inducible angiopoietin-2 expression is mimicked by iodonium compounds and occurs in the rat brain and skin in response to systemic hypoxia and tissue ischemia. Am J Pathol 2000, 156:2077-2089. 10.1016/S0002-9440(10)65079-1, 1850070, 10854229.
113. Oh H, Takagi H, Suzuma K, Otani A, Matsumura M, Honda Y. Hypoxia and vascular endothelial growth factor selectively up-regulate angiopoietin-2 in bovine microvascular endothelial cells. J Biol Chem 1999, 274:15732-15739. 10.1074/jbc.274.22.15732, 10336473.
114. Takagi H, Koyama S, Seike H, Oh H, Otani A, Matsumura M, Honda Y. Potential role of the angiopoietin/tie2 system in ischemia-induced retinal neovascularization. Invest Ophthalmol Vis Sci 2003, 44:393-402. 10.1167/iovs.02-0276, 12506101.
115. Nakaoka Y, Nishida K, Narimatsu M, Kamiya A, Minami T, Sawa H, Okawa K, Fujio Y, Koyama T, Maeda M, Sone M, Yamasaki S, Arai Y, Koh GY, Kodama T, Hirota H, Otsu K, Hirano T, Mochizuki N. Gab family proteins are essential for postnatal maintenance of cardiac function via neuregulin-1/ErbB signaling. J Clin Invest 2007, 117:1771-1781. 10.1172/JCI30651, 1888569, 17571162.
116. Korff T, Ernst E, Nobiling R, Feldner A, Reiss Y, Plate KH, Fiedler U, Augustin HG, Hecker M. Angiopoietin-1 mediates inhibition of hypertension-induced release of angiopoietin-2 from endothelial cells. Cardiovasc Res 2012, 94:510-518. 10.1093/cvr/cvs124, 22505659.
117. Adams S, Brown H, Turner G. Breaking down the blood-brain barrier: signaling a path to cerebral malaria?. Trends Parasitol 2002, 18:360-366. 10.1016/S1471-4922(02)02353-X, 12377286.
118. Turner G. Cerebral malaria. Brain Pathol 1997, 7:569-582. 10.1111/j.1750-3639.1997.tb01075.x, 9034566.
119. Erdman LK, Dhabangi A, Musoke C, Conroy AL, Hawkes M, Higgins S, Rajwans N, Wolofsky KT, Streiner DL, Liles WC, Cserti-Gazdewich CM, Kain KC. Combinations of host biomarkers predict mortality among Ugandan children with severe malaria: a retrospective case-control study. PLoS One 2011, 6:e17440. 10.1371/journal.pone.0017440, 3045453, 21364762.
120. Jenkins N, Wu Y, Chakravorty S, Kai O, Marsh K, Craig A. Plasmodium falciparum intercellular adhesion molecule-1-based cytoadherence-related signaling in human endothelial cells. J Infect Dis 2007, 196:321-327. 10.1086/518795, 1934551, 17570121.
121. Turner GD, Ly VC, Nguyen TH, Tran TH, Nguyen HP, Bethell D, Wyllie S, Louwrier K, Fox SB, Gatter KC, Day NP, Tran TH, White NJ, Berendt AR. Systemic endothelial activation occurs in both mild and severe malaria. Correlating dermal microvascular endothelial cell phenotype and soluble cell adhesion molecules with disease severity. Am J Pathol 1998, 152:1477-1487. 1858439, 9626052.
122. Porta J, Carota A, Pizzolato GP, Wildi E, Widmer MC, Margairaz C, Grau GE. Immunopathological changes in human cerebral malaria. Clin Neuropathol 1993, 12:142-146.
123. Grau GE, Pointaire P, Piguet PF, Vesin C, Rosen H, Stamenkovic I, Takei F, Vassalli P. Late administration of monoclonal antibody to leukocyte function-antigen 1 abrogates incipient murine cerebral malaria. Eur J Immunol 1991, 21:2265-2267. 10.1002/eji.1830210939, 1679717.
124. Grau GE, Tacchini-Cottier F, Vesin C, Milon G, Lou JN, Piguet PF, Juillard P. TNF-induced microvascular pathology: active role for platelets and importance of the LFA-1/ICAM-1 interaction. Eur Cytokine Netw 1993, 4:415-419.
125. Lucas R, Lou JN, Juillard P, Moore M, Bluethmann H, Grau GE. Respective role of TNF receptors in the development of experimental cerebral malaria. J Neuroimmunol 1997, 72:143-148. 10.1016/S0165-5728(96)00185-3, 9042106.
126. Kim I. Vascular Endothelial Growth Factor Expression of Intercellular Adhesion Molecule 1(ICAM-1), Vascular Cell Adhesion Molecule 1 (VCAM-1) and E-Selectin through Nuclear Factor -κB Activation in Endothelial Cells. J Biol Chem 2001, 276:7614-7620. 10.1074/jbc.M009705200, 11108718.
127. Conroy AL, Phiri H, Hawkes M, Glover S, Mallewa M, Seydel KB, Taylor TE, Molyneux ME, Kain KC. Endothelium-based biomarkers are associated with cerebral malaria in Malawian children: a retrospective case-control study. PLoS One 2010, 5:e15291. 10.1371/journal.pone.0015291, 3012131, 21209923.
128. Li J, Chang WL, Sun G, Chen HL, Specian RD, Berney SM, Kimpel D, Granger DN, Van der Heyde HC. Intercellular adhesion molecule 1 is important for the development of severe experimental malaria but is not required for leukocyte adhesion in the brain. J Investig Med 2003, 51:128-140.
129. Sun G, Chang WL, Li J, Berney SM, Kimpel D, Van der Heyde HC. Inhibition of platelet adherence to brain microvasculature protects against severe Plasmodium berghei malaria. Infect Immun 2003, 71:6553-6561. 10.1128/IAI.71.11.6553-6561.2003, 219602, 14573677.
130. Guo WP, Fu XG, Jiang SM, Wu JZ. Neuregulin-1 regulates the expression of Akt, Bcl-2, and Bad signaling after focal cerebral ischemia in rats. Biochem Cell Biol 2010, 88:649-654. 10.1139/O09-189, 20651836.
131. Xiao J, Li B, Zheng Z, Wang M, Peng J, Li Y, Li Z. Therapeutic effects of neuregulin-1 gene transduction in rats with myocardial infarction. Coron Artery Dis 2012, 23:460-468. 10.1097/MCA.0b013e32835877da, 22968213.
132. Gao R, Zhang J, Cheng L, Wu X, Dong W, Yang X, Li T, Liu X, Xu Y, Li X, Zhou M. A Phase II, randomized, double-blind, multicenter, based on standard therapy, placebo-controlled study of the efficacy and safety of recombinant human neuregulin-1 in patients with chronic heart failure. J Am Coll Cardiol 2010, 55:1907-1914. 10.1016/j.jacc.2009.12.044, 20430261.
133. Jabbour A, Hayward CS, Keogh AM, Kotlyar E, McCrohon JA, England JF, Amor R, Liu X, Li XY, Zhou MD, Graham RM, Macdonald PS. Parenteral administration of recombinant human neuregulin-1 to patients with stable chronic heart failure produces favourable acute and chronic haemodynamic responses. Eur J Heart Fail 2011, 13:83-92. 10.1093/eurjhf/hfq152, 20810473.
134. Xu Y, Li X, Liu X, Zhou M. Neuregulin-1/ErbB signaling and chronic heart failure. Adv Pharmacol 2010, 59:31-51.
135. Guo WP, Wang J, Li RX, Peng YW. Neuroprotective effects of neuregulin-1 in rat models of focal cerebral ischemia. Brain Res 2006, 1087:180-185. 10.1016/j.brainres.2006.03.007, 16616052.
136. Shyu WC, Lin SZ, Chiang MF, Yang HI, Thajeb P, Li H. Neuregulin-1 reduces ischemia-induced brain damage in rats. Neurobiol Aging 2004, 25:935-944. 10.1016/j.neurobiolaging.2003.10.012, 15212847.