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Experimental Cerebral Malaria Pathogenesis—Hemodynamics at the Blood Brain Barrier


Malaria remains one of the most serious health problems globally, but our understanding of the biology of the Plasmodium parasite and the pathogenesis of severe disease is still limited. Human cerebral malaria (HCM), a severe neurological complication characterized by rapid progression from headache to convulsions and unrousable coma, causes the death of hundreds of thousands of children in Africa annually. To better understand the pathogenesis of cerebral malaria, we imaged immune cells in brain microvessels of mice with experimental cerebral malaria (ECM) versus mice with malarial hyperparasitemia, which lack neurological impairment. Death from ECM closely correlated with plasma leakage, platelet marginalization, and the recruitment of significantly more leukocytes to postcapillary venules compared to hyperparasitemia. Leukocyte arrest in postcapillary venules caused a severe restriction in the venous blood flow and the immunomodulatory drug FTY720 prevents this recruitment and death from ECM. We propose a model for ECM in which leukocyte arrest, analogous to the sequestration of P. falciparum infected red blood cells in HCM, severely restricts the venous blood flow, which exacerbates edema and swelling of the brain at the agonal comatose stage of the infection, leading to intracranial hypertension and death.


Vyšlo v časopise: Experimental Cerebral Malaria Pathogenesis—Hemodynamics at the Blood Brain Barrier. PLoS Pathog 10(12): e32767. doi:10.1371/journal.ppat.1004528
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004528

Souhrn

Malaria remains one of the most serious health problems globally, but our understanding of the biology of the Plasmodium parasite and the pathogenesis of severe disease is still limited. Human cerebral malaria (HCM), a severe neurological complication characterized by rapid progression from headache to convulsions and unrousable coma, causes the death of hundreds of thousands of children in Africa annually. To better understand the pathogenesis of cerebral malaria, we imaged immune cells in brain microvessels of mice with experimental cerebral malaria (ECM) versus mice with malarial hyperparasitemia, which lack neurological impairment. Death from ECM closely correlated with plasma leakage, platelet marginalization, and the recruitment of significantly more leukocytes to postcapillary venules compared to hyperparasitemia. Leukocyte arrest in postcapillary venules caused a severe restriction in the venous blood flow and the immunomodulatory drug FTY720 prevents this recruitment and death from ECM. We propose a model for ECM in which leukocyte arrest, analogous to the sequestration of P. falciparum infected red blood cells in HCM, severely restricts the venous blood flow, which exacerbates edema and swelling of the brain at the agonal comatose stage of the infection, leading to intracranial hypertension and death.


Zdroje

1. WHO (2013) World Malaria Report: 2013. Geneva, Switzerland: World Health Organization.

2. MilnerDAJr (2010) Rethinking cerebral malaria pathology. Curr Op Infect Dis 23: 456–463.

3. HaldarK, MurphySC, MilnerDA, TaylorTE (2007) Malaria: mechanisms of erythrocytic infection and pathological correlates of severe disease. Annu Rev Pathol 2: 217–249.

4. ClarkIA, AwburnMM, WhittenRO, HarperCG, LiombaNG, et al. (2003) Tissue distribution of migration inhibitory factor and inducible nitric oxide synthase in falciparum malaria and sepsis in African children. Malaria J 2: 6.

5. HuntNH, GrauGE, EngwerdaC, BarnumSR, van der HeydeH, et al. (2010) Murine cerebral malaria: the whole story. Trends Parasitol 26: 272–274.

6. de SouzaJB, HafallaJCR, RileyEM, CouperKN (2010) Cerebral malaria: why experimental murine models are required to understand the pathogenesis of disease. Parasitology 137: 755–772.

7. WhiteVA, LewallenS, BeareNA, MolyneuxME, TaylorTE (2009) Retinal pathology of pediatric cerebral malaria in Malawi. PLoS ONE 4: e4317.

8. BeareNA, LewallenS, TaylorTE, MolyneuxME (2011) Redefining cerebral malaria by including malaria retinopathy. Future Microbiol 6: 349–355.

9. LouJ, LucasR, GrauGE (2001) Pathogenesis of cerebral malaria: recent experimental data and possible applications for humans. Clin Microbiol Rev 14: 810–820.

10. LambTJ, BrownDE, PotocnikAJ, LanghorneJ (2006) Insights into the immunopathogenesis of malaria using mouse models. Expert Rev Mol Med 8: 1–22.

11. EngwerdaC, BelnoueE, GrunerAC, ReniaL (2005) Experimental models of cerebral malaria. Curr Top Microbiol Immunol 297: 103–143.

12. ReniaL, PotterSM, MauduitM, RosaDS, KayibandaM, et al. (2006) Pathogenic T cells in cerebral malaria. Int J Parasitol 36: 547–554.

13. CombesV, ColtelN, FailleD, WassmerSC, GrauGE (2006) Cerebral malaria: role of microparticles and platelets in alterations of the blood-brain barrier. Int J Parasitol 36: 541–546.

14. GrauGE, PiguetPF, VassalliP, LambertPH (1989) Tumor-necrosis factor and other cytokines in cerebral malaria: experimental and clinical data. Immunol Rev 112: 49–70.

15. LanghorneJ, QuinSJ, SanniLA (2002) Mouse models of blood-stage malaria infections: immune responses and cytokines involved in protection and pathology. Chem Immunol 80: 204–228.

16. SanniLA (2001) The role of cerebral oedema in the pathogenesis of cerebral malaria. Redox Rep 6: 137–142.

17. PenetM-F, ViolaA, Confort-GounyS, Le FurY, DuhamelG, et al. (2005) Imaging experimental cerebral malaria in vivo: significant role of ischemic brain edema. J Neurosci 25: 7352–7358.

18. CoxD, McConkeyS (2010) The role of platelets in the pathogenesis of cerebral malaria. Cell Mol Life Sci 67: 557–568.

19. MoxonCA, HeydermanRS, WassmerSC (2009) Dysregulation of coagulation in cerebral malaria. Mol Biochem Parasitol 166: 99–108.

20. CombesV, RosenkranzAR, RedardM, PizzolatoG, LepidiH, et al. (2004) Pathogenic role of P-selectin in experimental cerebral malaria: importance of the endothelial compartment. Am J Pathol 164: 781–786.

21. NacerA, MovilaA, BaerK, MikolajczakSA, KappeSH, et al. (2012) Neuroimmunological blood brain barrier opening in experimental cerebral malaria. PLoS Pathog 8: e1002982.

22. FailleD, El-AssaadF, AlessiMC, FusaiT, CombesV, et al. (2009) Platelet-endothelial cell interactions in cerebral malaria: the end of a cordial understanding. Thromb Haemost 102: 1093–1102.

23. FailleD, CombesV, MitchellAJ, FontaineA, Juhan-VagueI, et al. (2009) Platelet microparticles: a new player in malaria parasite cytoadherence to human brain endothelium. FASEB J 23: 3449–3458.

24. BarbierM, FailleD, LoriodB, TextorisJ, CamusC, et al. (2011) Platelets alter gene expression profile in human brain endothelial cells in an in vitro model of cerebral malaria. PLoS ONE 6: e19651.

25. MfonkeuJB, GouadoI, KuateHF, ZambouO, CombesV, et al. (2010) Biochemical markers of nutritional status and childhood malaria severity in Cameroon. Br J Nutr 104: 886–892.

26. BelnoueE, KayibandaM, VigarioAM, DescheminJC, van RooijenN, et al. (2002) On the pathogenic role of brain-sequestered alphabeta CD8+ T cells in experimental cerebral malaria. J Immunol 169: 6369–6375.

27. ClaserC, MalleretB, GunSY, WongAY, ChangZW, et al. (2011) CD8 T cells and IFN-gamma mediate the time-dependent accumulation of infected red blood cells in deep organs during experimental cerebral malaria. PLoS ONE 6: e18720.

28. McQuillanJA, MitchellAJ, HoYF, CombesV, BallHJ, et al. (2011) Coincident parasite and CD8 T cell sequestration is required for development of experimental cerebral malaria. Int J Parasitol 41: 155–163.

29. HermsenC, van de WielT, MommersE, SauerweinR, ElingW (1997) Depletion of CD4+ or CD8+ T-cells prevents Plasmodium berghei induced cerebral malaria in end-stage disease. Parasitology 114 (Pt 1) 7–12.

30. AmanteFH, HaqueA, StanleyAC, Rivera FdeL, RandallLM, et al. (2010) Immune-mediated mechanisms of parasite tissue sequestration during experimental cerebral malaria. J Immunol 185: 3632–3642.

31. Franke-FayardB, JanseCJ, Cunha-RodriguesM, RamesarJ, BuscherP, et al. (2005) Murine malaria parasite sequestration: CD36 is the major receptor, but cerebral pathology is unlinked to sequestration. Proc Natl Acad Sci U S A 102: 11468–11473.

32. HaqueA, BestSE, UnossonK, AmanteFH, de LabastidaF, et al. (2011) Granzyme B expression by CD8+ T cells is required for the development of experimental cerebral malaria. J Immunol 186: 6148–6156.

33. NitcheuJ, BonduelleO, CombadiereC, TefitM, SeilheanD, et al. (2003) Perforin-dependent brain-infiltrating cytotoxic CD8+ T lymphocytes mediate experimental cerebral malaria pathogenesis. J Immunol 170: 2221–2228.

34. BaptistaFG, PamplonaA, PenaAC, MotaMM, PiedS, et al. (2010) Accumulation of Plasmodium berghei-infected red blood cells in the brain is crucial for the development of cerebral malaria in mice. Infect Immun 78: 4033–4039.

35. AmanteFH, HaqueA, StanleyAC, RiveraFdL, RandallLM, et al. (2010) Immune-mediated mechanisms of parasite tissue sequestration during experimental cerebral malaria. J Immunol 185: 3632–3642.

36. PaisTF, ChatterjeeS (2005) Brain macrophage activation in murine cerebral malaria precedes accumulation of leukocytes and CD8+ T cell proliferation. J Neuroimmunol 163: 73–83.

37. PotterS, Chan-LingT, BallHJ, MansourH, MitchellA, et al. (2006) Perforin mediated apoptosis of cerebral microvascular endothelial cells during experimental cerebral malaria. Int J Parasitol 36: 485–496.

38. OwensT, BechmannI, EngelhardtB (2008) Perivascular spaces and the two steps to neuroinflammation. J Neuropathol Exp Neurol 67: 1113–1121.

39. FinneyCA, HawkesCA, KainDC, DhabangiA, MusokeC, et al. (2011) S1P is associated with protection in human and experimental cerebral malaria. Mol Med 17: 717–725.

40. KippM, AmorS (2012) FTY720 on the way from the base camp to the summit of the mountain: relevance for remyelination. Mult Scler 18: 258–263.

41. HlaT, BrinkmannV (2011) Sphingosine 1-phosphate (S1P): Physiology and the effects of S1P receptor modulation. Neurology 76: S3–8.

42. BrinkmannV, BillichA, BaumrukerT, HeiningP, SchmouderR, et al. (2010) Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis. Nat Rev Drug Discov 9: 883–897.

43. MetzlerB, GfellerP, WieczorekG, LiJ, Nuesslein-HildesheimB, et al. (2008) Modulation of T cell homeostasis and alloreactivity under continuous FTY720 exposure. Int Immunol 20: 633–644.

44. TaylorPA, EhrhardtMJ, LeesCJ, TolarJ, WeigelBJ, et al. (2007) Insights into the mechanism of FTY720 and compatibility with regulatory T cells for the inhibition of graft-versus-host disease (GVHD). Blood 110: 3480–3488.

45. IdzkoM, HammadH, van NimwegenM, KoolM, MullerT, et al. (2006) Local application of FTY720 to the lung abrogates experimental asthma by altering dendritic cell function. J Clin Invest 116: 2935–2944.

46. BrinkmannV, CysterJG, HlaT (2004) FTY720: sphingosine 1-phosphate receptor-1 in the control of lymphocyte egress and endothelial barrier function. Am J Transplant 4: 1019–1025.

47. SanchezT, Estrada-HernandezT, PaikJH, WuMT, VenkataramanK, et al. (2003) Phosphorylation and action of the immunomodulator FTY720 inhibits vascular endothelial cell growth factor-induced vascular permeability. J Biol Chem 278: 47281–47290.

48. LeeMJ, ThangadaS, ClaffeyKP, AncellinN, LiuCH, et al. (1999) Vascular endothelial cell adherens junction assembly and morphogenesis induced by sphingosine-1-phosphate. Cell 99: 301–312.

49. DevKK, MullershausenF, MattesH, KuhnRR, BilbeG, et al. (2008) Brain sphingosine-1-phosphate receptors: implication for FTY720 in the treatment of multiple sclerosis. Pharmacol Ther 117: 77–93.

50. NewtonCR, KirkhamFJ, WinstanleyPA, PasvolG, PeshuN, et al. (1991) Intracranial pressure in African children with cerebral malaria. Lancet 337: 573–576.

51. ShihAY, BlinderP, TsaiPS, FriedmanB, StanleyG, et al. (2013) The smallest stroke: occlusion of one penetrating vessel leads to infarction and a cognitive deficit. Nat Neurosci 16: 55–63.

52. RisserL, PlouraboueF, SteyerA, CloetensP, Le DucG, et al. (2007) From homogeneous to fractal normal and tumorous microvascular networks in the brain. J Cereb Blood Flow Metab 27: 293–303.

53. MedanaIM, TurnerGD (2006) Human cerebral malaria and the blood-brain barrier. Int J Parasitol 36: 555–568.

54. KampondeniSD, PotchenMJ, BeareNA, SeydelKB, GloverSJ, et al. (2013) MRI findings in a cohort of brain injured survivors of pediatric cerebral malaria. Am J Trop Med Hyg 88: 542–546.

55. Seydel K, Kampondeni S, Potchen M, Birbeck G, Molyneux M, et al.. (2011) Clinical Correlates of Magnetic Resonance Imaging in Pediatric Cerebral Malaria. ASTMH Annual Meeting Philadelphia, PA: American Society of Tropical Medicine and Hygiene.

56. FordAL, GoodsallAL, HickeyWF, SedgwickJD (1995) Normal adult ramified microglia separated from other central nervous system macrophages by flow cytometric sorting. Phenotypic differences defined and direct ex vivo antigen presentation to myelin basic protein-reactive CD4+ T cells compared. J Immunol 154: 4309–4321.

57. DietrichJB (2002) The adhesion molecule ICAM-1 and its regulation in relation with the blood-brain barrier. J Neuroimmunol 128: 58–68.

58. KimH, HigginsS, LilesWC, KainKC (2011) Endothelial activation and dysregulation in malaria: a potential target for novel therapeutics. Curr Opin Hematol 18: 177–185.

59. ChakravortySJ, CraigA (2005) The role of ICAM-1 in Plasmodium falciparum cytoadherence. Eur J Cell Biol 84: 15–27.

60. ShermanIW, EdaS, WinogradE (2003) Cytoadherence and sequestration in Plasmodium falciparum: defining the ties that bind. Microbes Infect/Institut Pasteur 5: 897–909.

61. HoM, WhiteNJ (1999) Molecular mechanisms of cytoadherence in malaria. Am J Physiol 276: C1231–1242.

62. AmaniV, VigarioAM, BelnoueE, MarussigM, FonsecaL, et al. (2000) Involvement of IFN-gamma receptor-medicated signaling in pathology and anti-malarial immunity induced by Plasmodium berghei infection. Eur J Immunol 30: 1646–1655.

63. KaulDK, LiuXD, NagelRL, ShearHL (1998) Microvascular hemodynamics and in vivo evidence for the role of intercellular adhesion molecule-1 in the sequestration of infected red blood cells in a mouse model of lethal malaria. Am J Trop Med Hyg 58: 240–247.

64. ShearHL, MarinoMW, WanidworanunC, BermanJW, NagelRL (1998) Correlation of increased expression of intercellular adhesion molecule-1, but not high levels of tumor necrosis factor-alpha, with lethality of Plasmodium yoelii 17XL, a rodent model of cerebral malaria. Am J Trop Med Hyg 59: 852–858.

65. HaqueA, EchchannaouiH, SeguinR, SchwartzmanJ, KasperLH, et al. (2001) Cerebral malaria in mice: interleukin-2 treatment induces accumulation of gammadelta T cells in the brain and alters resistant mice to susceptible-like phenotype. Am J Pathol 158: 163–172.

66. RamosTN, BullardDC, DarleyMM, McDonaldK, CrawfordDF, et al. (2013) Experimental cerebral malaria develops independently of endothelial expression of intercellular adhesion molecule-1 (icam-1). J Biol Chem 288: 10962–10966.

67. GoebelerM, RothJ, KunzM, SorgC (1993) Expression of intercellular adhesion molecule-1 by murine macrophages is up-regulated during differentiation and inflammatory activation. Immunobiology 188: 159–171.

68. RuettenH, ThiemermannC, PerrettiM (1999) Upregulation of ICAM-1 expression on J774.2 macrophages by endotoxin involves activation of NF-kappaB but not protein tyrosine kinase: comparison to induction of iNOS. Mediators Inflamm 8: 77–84.

69. NovosadJ, HolickaM, NovosadovaM, KrejsekJ, KrcmovaI (2011) Rapid onset of ICAM-1 expression is a marker of effective macrophages activation during infection of Francisella tularensis LVS in vitro. Folia Microbiol (Praha) 56: 149–154.

70. Fattal-GermanM, Le Roy LadurieF, LecerfF, Berrih-AkninS (1996) Expression of ICAM-1 and TNF alpha in human alveolar macrophages from lung-transplant recipients. Ann N Y Acad Sci 796: 138–148.

71. JenneCN, KubesP (2013) Immune surveillance by the liver. Nat Immunol 14: 996–1006.

72. OchoaCD, WuS, StevensT (2010) New developments in lung endothelial heterogeneity: Von Willebrand factor, P-selectin, and the Weibel-Palade body. Semin Thromb Hemost 36: 301–308.

73. LowensteinCJ, MorrellCN, YamakuchiM (2005) Regulation of Weibel-Palade body exocytosis. Trends Cardiovasc Med 15: 302–308.

74. WassmerSC, CombesV, CandalFJ, Juhan-VagueI, GrauGE (2006) Platelets potentiate brain endothelial alterations induced by Plasmodium falciparum. Infection and Immunity 74: 645–653.

75. WassmerSC, LepolardC, TraoreB, PouvelleB, GysinJ, et al. (2004) Platelets reorient Plasmodium falciparum-infected erythrocyte cytoadhesion to activated endothelial cells. J Infect Dis 189: 180–189.

76. GrauGE, MackenzieCD, CarrRA, RedardM, PizzolatoG, et al. (2003) Platelet accumulation in brain microvessels in fatal pediatric cerebral malaria. J Infect Dis 187: 461–466.

77. LinaresM, Marin-GarciaP, Perez-BenaventeS, Sanchez-NogueiroJ, PuyetA, et al. (2012) Brain-derived neurotrophic factor and the course of experimental cerebral malaria. Brain Res 1490: 210–224.

78. ZaniniGM, CabralesP, BarkhoW, FrangosJA, CarvalhoLJ (2011) Exogenous nitric oxide decreases brain vascular inflammation, leakage and venular resistance during Plasmodium berghei ANKA infection in mice. J Neuroinflammation 8: 66.

79. BridgesDJ, BunnJ, van MourikJA, GrauG, PrestonRJ, et al. (2010) Rapid activation of endothelial cells enables Plasmodium falciparum adhesion to platelet-decorated von Willebrand factor strings. Blood 115: 1472–1474.

80. CamererE, RegardJB, CornelissenI, SrinivasanY, DuongDN, et al. (2009) Sphingosine-1-phosphate in the plasma compartment regulates basal and inflammation-induced vascular leak in mice. J Clin Invest 119: 1871–1879.

81. OoML, ChangSH, ThangadaS, WuMT, RezaulK, et al. (2011) Engagement of S1P(1)-degradative mechanisms leads to vascular leak in mice. J Clin Invest 121: 2290–2300.

82. FrevertU, NacerA (2013) Immunobiology of Plasmodium in liver and brain. Parasite Immunol 35: 267–282.

83. PriesAR, SecombTW, GaehtgensP (2000) The endothelial surface layer. Pflugers Arch 440: 653–666.

84. ReitsmaS, SlaafDW, VinkH, van ZandvoortMA, oude EgbrinkMG (2007) The endothelial glycocalyx: composition, functions, and visualization. Pflugers Arch 454: 345–359.

85. FelsJ, JeggleP, LiashkovichI, PetersW, OberleithnerH (2014) Nanomechanics of vascular endothelium. Cell Tissue Res 355: 727–737.

86. AlphonsusCS, RodsethRN (2014) The endothelial glycocalyx: a review of the vascular barrier. Anaesthesia 69: 777–784.

87. BerendtAR, TumerGD, NewboldCI (1994) Cerebral malaria: the sequestration hypothesis. Parasitol Today 10: 412–414.

88. ClarkIA, RockettKA (1994) The cytokine theory of human cerebral malaria. Parasitol Today 10: 410–412.

89. GrauGE, de KossodoS (1994) Cerebral malaria: mediators, mechanical obstruction or more? Parasitol Today 10: 408–409.

90. CabralesP, MartinsYC, OngPK, ZaniniGM, FrangosJA, et al. (2013) Cerebral tissue oxygenation impairment during experimental cerebral malaria. Virulence 4: 686–697.

91. KoutsiarisAG, TachmitziSV, BatisN, KotoulaMG, KarabatsasCH, et al. (2007) Volume flow and wall shear stress quantification in the human conjunctival capillaries and post-capillary venules in vivo. Biorheology 44: 375–386.

92. AmpawongS, CombesV, HuntNH, RadfordJ, Chan-LingT, et al. (2011) Quantitation of brain edema and localisation of aquaporin 4 expression in relation to susceptibility to experimental cerebral malaria. Int J Clin Exp Pathol 4: 566–574.

93. MohantyS, MishraSK, PatnaikR, DuttAK, PradhanS, et al. (2011) Brain swelling and mannitol therapy in adult cerebral malaria: a randomized trial. Clin Infect Dis 53: 349–355.

94. LooareesuwanS, WilairatanaP, KrishnaS, KendallB, VannaphanS, et al. (1995) Magnetic resonance imaging of the brain in patients with cerebral malaria. Clin Infect Dis 21: 300–309.

95. NewtonCR, CrawleyJ, SowumniA, WaruiruC, MwangiI, et al. (1997) Intracranial hypertension in Africans with cerebral malaria. Arch Dis Child 76: 219–226.

96. WallerD, CrawleyJ, NostenF, ChapmanD, KrishnaS, et al. (1991) Intracranial pressure in childhood cerebral malaria. Trans R Soc Trop Med Hyg 85: 362–364.

97. MurphyS, Cserti-GazdewichC, DhabangiA, MusokeC, Nabukeera-BarungiN, et al. (2011) Ultrasound findings in Plasmodium falciparum malaria: a pilot study. Pediatr Crit Care Med 12: e58–63.

98. NewtonCR, MarshK, PeshuN, KirkhamFJ (1996) Perturbations of cerebral hemodynamics in Kenyans with cerebral malaria. Pediatr Neurol 15: 41–49.

99. PotchenMJ, KampondeniSD, SeydelKB, BirbeckGL, HammondCA, et al. (2012) Acute brain MRI findings in 120 Malawian children with cerebral malaria: new insights into an ancient disease. AJNR Am J Neuroradiol 33: 1740–1746.

100. CabralesP, ZaniniGM, MeaysD, FrangosJA, CarvalhoLJM (2010) Murine cerebral malaria is associated with a vasospasm-like microcirculatory dysfunction, and survival upon rescue treatment is markedly increased by nimodipine. Am J Pathol 176: 1306–1315.

101. KennanRP, MachadoFS, LeeSC, DesruisseauxMS, WittnerM, et al. (2005) Reduced cerebral blood flow and N-acetyl aspartate in a murine model of cerebral malaria. Parasitol Res 96: 302–307.

102. MartinsYC, Daniel-RibeiroCT (2013) A new hypothesis on the manifestation of cerebral malaria: The secret is in the liver. Med Hypotheses 81: 777–783.

103. HoltmaatA, BonhoefferT, ChowDK, ChuckowreeJ, De PaolaV, et al. (2009) Long-term, high-resolution imaging in the mouse neocortex through a chronic cranial window. Nat Protocols 4: 1128–1144.

104. MostanyR, Portera-CailliauC (2008) A craniotomy surgery procedure for chronic brain imaging. J Vis Exp e680 610.3791/3680 DOI: 3710.3791/3680

105. King-VanVlackCE, MewburnJD, ChaplerCK, MacDonaldPH (2003) Hemodynamic and proinflammatory actions of endothelin-1 in guinea pig small intestine submucosal microcirculation. Am J Physiol Gastrointest Liver Physiol 284: G940–948.

106. CalleraGE, TouyzRM, TeixeiraSA, MuscaraMN, CarvalhoMH, et al. (2003) ETA receptor blockade decreases vascular superoxide generation in DOCA-salt hypertension. Hypertension 42: 811–817.

107. McCarronRM, WangL, StanimirovicDB, SpatzM (1993) Endothelin induction of adhesion molecule expression on human brain microvascular endothelial cells. Neurosci Lett 156: 31–34.

108. FreemanBD, MachadoFS, TanowitzHB, DesruisseauxMS (2014) Endothelin-1 and its role in the pathogenesis of infectious diseases. Life Sci. E-pub ahead of print doi:10.1016/j.lfs.2014.04.021

109. MachadoFS, DesruisseauxMS, Nagajyothi, KennanRP, HetheringtonHP, et al. (2006) Endothelin in a murine model of cerebral malaria. Exp Biol Med (Maywood) 231: 1176–1181.

110. DaiM, FreemanB, BrunoFP, ShikaniHJ, TanowitzHB, et al. (2012) The novel ETA receptor antagonist HJP-272 prevents cerebral microvascular hemorrhage in cerebral malaria and synergistically improves survival in combination with an artemisinin derivative. Life Sci 91: 687–692.

111. BasilicoN, SpecialeL, ParapiniS, FerranteP, TaramelliD (2002) Endothelin-1 production by a microvascular endothelial cell line treated with Plasmodium falciparum parasitized red blood cells. Clin Sci (Lond) 103 Suppl 48: 464S–466S.

112. WenischC, WenischH, WilairatanaP, LooareesuwanS, VannaphanS, et al. (1996) Big endothelin in patients with complicated Plasmodium falciparum malaria. J Infect Dis 173: 1281–1284.

113. Martins C, Tanowitz H, Weiss L, Desruisseaux MS (2014) Endothelin-1 treatment induces experimental cerebral malaria in Plasmodium berghei NK65 infected mice. Malaria 2014: Advances in Pathophysiology, Biology and Drug Development New York, NY: New York Academy of Sciences.

114. SirvioML, MetsarinneK, SaijonmaaO, FyhrquistF (1990) Tissue distribution and half-life of 125I-endothelin in the rat: importance of pulmonary clearance. Biochem Biophys Res Commun 167: 1191–1195.

115. WillenborgDO, StaykovaM, FordhamS, O'BrienN, LinaresD (2007) The contribution of nitric oxide and interferon gamma to the regulation of the neuro-inflammation in experimental autoimmune encephalomyelitis. J Neuroimmunol 191: 16–25.

116. OngPK, MelchiorB, MartinsYC, HoferA, Orjuela-SanchezP, et al. (2013) Nitric oxide synthase dysfunction contributes to impaired cerebroarteriolar reactivity in experimental cerebral malaria. PLoS Pathog 9: e1003444.

117. Orjuela-SanchezP, OngPK, ZaniniGM, MelchiorB, MartinsYC, et al. (2013) Transdermal glyceryl trinitrate as an effective adjunctive treatment with artemether for late-stage experimental cerebral malaria. Antimicrob Agents Chemother 57: 5462–5471.

118. ZaniniGM, MartinsYC, CabralesP, FrangosJA, CarvalhoLJ (2012) S-nitrosoglutathione prevents experimental cerebral malaria. J Neuroimmune Pharmacol 7: 477–487.

119. CabralesP, ZaniniGM, MeaysD, FrangosJA, CarvalhoLJ (2011) Nitric oxide protection against murine cerebral malaria is associated with improved cerebral microcirculatory physiology. J Infect Dis 203: 1454–1463.

120. SerghidesL, KimH, LuZ, KainDC, MillerC, et al. (2011) Inhaled nitric oxide reduces endothelial activation and parasite accumulation in the brain, and enhances survival in experimental cerebral malaria. PLoS One 6: e27714.

121. HawkesM, OpokaRO, NamasopoS, MillerC, ConroyAL, et al. (2011) Nitric oxide for the adjunctive treatment of severe malaria: hypothesis and rationale. Med Hypotheses 77: 437–444.

122. ImaiT, ShenJ, ChouB, DuanX, TuL, et al. (2010) Involvement of CD8+ T cells in protective immunity against murine blood-stage infection with Plasmodium yoelii 17XL strain. Eur J Immunol 40: 1053–1061.

123. VozaT, VigarioAM, BelnoueE, GrunerAC, DescheminJ-C, et al. (2005) Species-specific inhibition of cerebral malaria in mice coinfected with Plasmodium spp. Infect Immun 73: 4777–4786.

124. ClarkCJ, PhillipsRS (2011) Cerebral malaria protection in mice by species-specific Plasmodium coinfection is associated with reduced CC chemokine levels in the brain. Parasite Immunol 33: 637–641.

125. ShivtielS, KolletO, LapidK, SchajnovitzA, GoichbergP, et al. (2008) CD45 regulates retention, motility, and numbers of hematopoietic progenitors, and affects osteoclast remodeling of metaphyseal trabecules. J Exp Med 205: 2381–2395.

126. SilverbergJ, GinsburgD, OrmanR, AmassianV, DurkinHG, et al. (2010) Lymphocyte infiltration of neocortex and hippocampus after a single brief seizure in mice. Brain Behav Immun 24: 263–272.

127. CambiaggiC, ScupoliMT, CestariT, GerosaF, CarraG, et al. (1992) Constitutive expression of CD69 in interspecies T-cell hybrids and locus assignment to human chromosome 12. Immunogenetics 36: 117–120.

128. ToughDF, SunS, ZhangX, SprentJ (1999) Stimulation of naive and memory T cells by cytokines. Immunol Rev 170: 39–47.

129. FauconnierM, PalomoJ, BourigaultML, MemeS, SzeremetaF, et al. (2012) IL-12Rbeta2 is essential for the development of experimental cerebral malaria. J Immunol 188: 1905–1914.

130. BoubouMI, ColletteA, VoegtleD, MazierD, CazenavePA, et al. (1999) T cell response in malaria pathogenesis: selective increase in T cells carrying the TCR V(beta)8 during experimental cerebral malaria. Int Immunol 11: 1553–1562.

131. Silva-FilhoJL, SouzaMC, Ferreira-DasilvaCT, SilvaLS, CostaMF, et al. (2013) Angiotensin II is a new component involved in splenic T lymphocyte responses during Plasmodium berghei ANKA infection. PLoS One 8: e62999.

132. BoeufPS, LoizonS, AwandareGA, TettehJK, AddaeMM, et al. (2012) Insights into deregulated TNF and IL-10 production in malaria: implications for understanding severe malarial anaemia. Malar J 11: 253.

133. AnadaY, IgarashiY, KiharaA (2007) The immunomodulator FTY720 is phosphorylated and released from platelets. Eur J Pharmacol 568: 106–111.

134. KiharaA, IgarashiY (2008) Production and release of sphingosine 1-phosphate and the phosphorylated form of the immunomodulator FTY720. Biochim Biophys Acta 1781: 496–502.

135. GarciaJG, LiuF, VerinAD, BirukovaA, DechertMA, et al. (2001) Sphingosine 1-phosphate promotes endothelial cell barrier integrity by Edg-dependent cytoskeletal rearrangement. J Clin Invest 108: 689–701.

136. SchaphorstKL, ChiangE, JacobsKN, ZaimanA, NatarajanV, et al. (2003) Role of sphingosine-1 phosphate in the enhancement of endothelial barrier integrity by platelet-released products. Am J Physiol Lung Cell Mol Physiol 285: L258–267.

137. ConroyAL, GloverSJ, HawkesM, ErdmanLK, SeydelKB, et al. (2012) Angiopoietin-2 levels are associated with retinopathy and predict mortality in Malawian children with cerebral malaria: a retrospective case-control study. Crit Care Med 40: 952–959.

138. ConroyAL, LaffertyEI, LovegroveFE, KrudsoodS, TangpukdeeN, et al. (2009) Whole blood angiopoietin-1 and -2 levels discriminate cerebral and severe (non-cerebral) malaria from uncomplicated malaria. Malar J 8: 295.

139. LovegroveFE, TangpukdeeN, OpokaRO, LaffertyEI, RajwansN, et al. (2009) Serum angiopoietin-1 and -2 levels discriminate cerebral malaria from uncomplicated malaria and predict clinical outcome in African children. PLoS ONE 4: e4912.

140. JainV, LucchiNW, WilsonNO, BlackstockAJ, NagpalAC, et al. (2011) Plasma levels of angiopoietin-1 and -2 predict cerebral malaria outcome in Central India. Malar J 10: 383.

141. SenaldiG, VesinC, ChangR, GrauGE, PiguetPF (1994) Role of polymorphonuclear neutrophil leukocytes and their integrin CD11a (LFA-1) in the pathogenesis of severe murine malaria. Infect Immun 62: 1144–1149.

142. RossiB, AngiariS, ZenaroE, BuduiSL, ConstantinG (2011) Vascular inflammation in central nervous system diseases: adhesion receptors controlling leukocyte-endothelial interactions. J Leukoc Biol 89: 539–556.

143. HuntNH, GolenserJ, Chan-LingT, ParekhS, RaeC, et al. (2006) Immunopathogenesis of cerebral malaria. Int J Parasitol 36: 569–582.

144. MedanaIM, HuntNH, Chan-LingT (1997) Early activation of microglia in the pathogenesis of fatal murine cerebral malaria. Glia 19: 91–103.

145. BelnoueE, KayibandaM, DescheminJC, ViguierM, MackM, et al. (2003) CCR5 deficiency decreases susceptibility to experimental cerebral malaria. Blood 101: 4253–4259.

146. PenetMF, KoberF, Confort-GounyS, Le FurY, DalmassoC, et al. (2007) Magnetic resonance spectroscopy reveals an impaired brain metabolic profile in mice resistant to cerebral malaria infected with Plasmodium berghei ANKA. J Biol Chem 282: 14505–14514.

147. GaleaI, FeltonLM, WatersS, van RooijenN, PerryVH, et al. (2008) Immune-to-brain signalling: the role of cerebral CD163-positive macrophages. Neurosci Lett 448: 41–46.

148. GaleaI, PalinK, NewmanTA, Van RooijenN, PerryVH, et al. (2005) Mannose receptor expression specifically reveals perivascular macrophages in normal, injured, and diseased mouse brain. Glia 49: 375–384.

149. PolflietMM, ZwijnenburgPJ, van FurthAM, van der PollT, DoppEA, et al. (2001) Meningeal and perivascular macrophages of the central nervous system play a protective role during bacterial meningitis. J Immunol 167: 4644–4650.

150. HowlandSW, PohCM, GunSY, ClaserC, MalleretB, et al. (2013) Brain microvessel cross-presentation is a hallmark of experimental cerebral malaria. EMBO Mol Med 5: 916–931.

151. WangNK, LaiCC, LiuCH, YehLK, ChouCL, et al. (2013) Origin of fundus hyperautofluorescent spots and their role in retinal degeneration in a mouse model of Goldmann-Favre syndrome. Dis Model Mech 6: 1113–1122.

152. PaiS, QinJ, CavanaghL, MitchellA, El-AssaadF, et al. (2014) Real-time imaging reveals the dynamics of leukocyte behaviour during experimental cerebral malaria pathogenesis. PLoS Pathog 10: e1004236.

153. Fernandez-ReyesD, CraigAG, KyesSA, PeshuN, SnowRW, et al. (1997) A high frequency African coding polymorphism in the N-terminal domain of ICAM-1 predisposing to cerebral malaria in Kenya. Hum Mol Genet 6: 1357–1360.

154. OckenhouseCF, TegoshiT, MaenoY, BenjaminC, HoM, et al. (1992) Human vascular endothelial cell adhesion receptors for Plasmodium falciparum-infected erythrocytes: roles for endothelial leukocyte adhesion molecule 1 and vascular cell adhesion molecule 1. J Exp Med 176: 1183–1189.

155. OcholaLB, SiddondoBR, OchollaH, NkyaS, KimaniEN, et al. (2011) Specific receptor usage in Plasmodium falciparum cytoadherence is associated with disease outcome. PLoS ONE 6: e14741.

156. CraigA, Fernandez-ReyesD, MesriM, McDowallA, AltieriDC, et al. (2000) A functional analysis of a natural variant of intercellular adhesion molecule-1 (ICAM-1Kilifi). Hum Mol Genet 9: 525–530.

157. SilamutK, PhuNH, WhittyC, TurnerGD, LouwrierK, et al. (1999) A quantitative analysis of the microvascular sequestration of malaria parasites in the human brain. Am J Pathol 155: 395–410.

158. NewboldC, WarnP, BlackG, BerendtA, CraigA, et al. (1997) Receptor-specific adhesion and clinical disease in Plasmodium falciparum. Am J Trop Med Hyg 57: 389–398.

159. PinoP, TaoufiqZ, NitcheuJ, VouldoukisI, MazierD (2005) Blood-brain barrier breakdown during cerebral malaria: suicide or murder? Thromb Haemost 94: 336–340.

160. GrauGE, Tacchini-CottierF, VesinC, MilonG, LouJN, et al. (1993) TNF-induced microvascular pathology: active role for platelets and importance of the LFA-1/ICAM-1 interaction. Eur Cytokine Netw 4: 415–419.

161. FavreN, Da LaperousazC, RyffelB, WeissNA, ImhofBA, et al. (1999) Role of ICAM-1 (CD54) in the development of murine cerebral malaria. Microbes Infect 1: 961–968.

162. LiJ, ChangWL, SunG, ChenHL, SpecianRD, et al. (2003) 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 51: 128–140.

163. BauerPR, Van Der HeydeHC, SunG, SpecianRD, GrangerDN (2002) Regulation of endothelial cell adhesion molecule expression in an experimental model of cerebral malaria. Microcirculation 9: 463–470.

164. WeiserS, MiuJ, BallHJ, HuntNH (2007) Interferon-gamma synergises with tumour necrosis factor and lymphotoxin-alpha to enhance the mRNA and protein expression of adhesion molecules in mouse brain endothelial cells. Cytokine 37: 84–91.

165. ZhouH, AndoneguiG, WongCH, KubesP (2009) Role of endothelial TLR4 for neutrophil recruitment into central nervous system microvessels in systemic inflammation. J Immunol 183: 5244–5250.

166. ZhouH, LapointeBM, ClarkSR, ZbytnuikL, KubesP (2006) A requirement for microglial TLR4 in leukocyte recruitment into brain in response to lipopolysaccharide. J Immunol 177: 8103–8110.

167. GriffithsM, NealJW, GasqueP (2007) Innate immunity and protective neuroinflammation: new emphasis on the role of neuroimmune regulatory proteins. Int Rev Neurobiol 82: 29–55.

168. LloydKL, KubesP (2006) GPI-linked endothelial CD14 contributes to the detection of LPS. Am J Physiol Heart Circ Physiol 291: H473–481.

169. OakleyMS, MajamV, MahajanB, GeraldN, AnantharamanV, et al. (2009) Pathogenic roles of CD14, galectin-3, and OX40 during experimental cerebral malaria in mice. PLoS ONE 4: e6793.

170. DevittA, MoffattOD, RaykundaliaC, CapraJD, SimmonsDL, et al. (1998) Human CD14 mediates recognition and phagocytosis of apoptotic cells. Nature 392: 505–509.

171. WieseL, HempelC, PenkowaM, KirkbyN, KurtzhalsJA (2008) Recombinant human erythropoietin increases survival and reduces neuronal apoptosis in a murine model of cerebral malaria. Malar J 7: 3.

172. WieseL, KurtzhalsJA, PenkowaM (2006) Neuronal apoptosis, metallothionein expression and proinflammatory responses during cerebral malaria in mice. Exp Neurol 200: 216–226.

173. LacknerP, BurgerC, PfallerK, HeusslerV, HelbokR, et al. (2007) Apoptosis in experimental cerebral malaria: spatial profile of cleaved caspase-3 and ultrastructural alterations in different disease stages. Neuropathol Appl Neurobiol 33: 560–571.

174. LingZL, CombesV, GrauGE, KingNJ (2011) Microparticles as immune regulators in infectious disease - an opinion. Front Immunol 2: 67.

175. El-AssaadF, WhewayJ, HuntNH, GrauGE, CombesV (2014) Production, fate and pathogenicity of plasma microparticles in murine cerebral malaria. PLoS Pathog 10: e1003839.

176. VasinaEM, CauwenberghsS, FeijgeMA, HeemskerkJW, WeberC, et al. (2011) Microparticles from apoptotic platelets promote resident macrophage differentiation. Cell Death Dis 2: e211.

177. MacPhersonGG, WarrellMJ, WhiteNJ, LooareesuwanS, WarrellDA (1985) Human cerebral malaria a quantitative ultrastructural analysis of parasitized erythrocyte sequestration. ajp 119: 385–401.

178. ClarkIA, BuddAC, AllevaLM, CowdenWB (2006) Human malarial disease: a consequence of inflammatory cytokine release. Malar J 5: 85.

179. ClarkIA, SchofieldL (2000) Pathogenesis of malaria. Parasitol Today 16: 451–454.

180. GrauGE, PointaireP, PiguetPF, VesinC, RosenH, et al. (1991) Late administration of monoclonal antibody to leukocyte function-antigen 1 abrogates incipient murine cerebral malaria. Eur J Immunol 21: 2265–2267.

181. FalangaPB, ButcherEC (1991) Late treatment with anti-LFA-1 (CD11a) antibody prevents cerebral malaria in a mouse model. Eur J Immunol 21: 2259–2263.

182. FrevertU, NacerA, CabreraM, MovilaA, LeberlM (2014) Imaging Plasmodium immunobiology in the liver, brain, and lung. Parasitol Int 63: 171–186.

183. van der HeydeHC, GramagliaI, SunG, WoodsC (2005) Platelet depletion by anti-CD41 (alphaIIb) mAb injection early but not late in the course of disease protects against Plasmodium berghei pathogenesis by altering the levels of pathogenic cytokines. Blood 105: 1956–1963.

184. SunG, ChangWL, LiJ, BerneySM, KimpelD, et al. (2003) Inhibition of platelet adherence to brain microvasculature protects against severe Plasmodium berghei malaria. Infect Immun 71: 6553–6561.

185. Granger DN, Senchenkova E (2010) Endothelial Barrier Dysfunction. Inflammation and the Microcirculation. San Rafael (CA): Morgan& Claypool Lifesciences.

186. LawsonC, WolfS (2009) ICAM-1 signaling in endothelial cells. Pharmacol Rep 61: 22–32.

187. SumaginR, LomakinaE, SareliusIH (2008) Leukocyte-endothelial cell interactions are linked to vascular permeability via ICAM-1-mediated signaling. Am J Physiol Heart Circ Physiol 295: H969–H977.

188. LiN (2008) Platelet-lymphocyte cross-talk. J Leukoc Biol 83: 1069–1078.

189. IdroR, CarterJA, FeganG, NevilleBG, NewtonCR (2006) Risk factors for persisting neurological and cognitive impairments following cerebral malaria. Arch Dis Child 91: 142–148.

190. van HensbroekMB, PalmerA, JaffarS, SchneiderG, KwiatkowskiD (1997) Residual neurologic sequelae after childhood cerebral malaria. J Pediatr 131: 125–129.

191. BeareNA, GloverSJ, LewallenS, TaylorTE, HardingSP, et al. (2012) Prevalence of raised intracranial pressure in cerebral malaria detected by optic nerve sheath ultrasound. Am J Trop Med Hyg 87: 985–988.

192. IdroR, Kakooza-MwesigeA, BalyejjussaS, MirembeG, MugashaC, et al. (2010) Severe neurological sequelae and behaviour problems after cerebral malaria in Ugandan children. BMC Res Notes 3: 104.

193. FrevertU, NacerA (2014) Fatal cerebral malaria: a venous efflux problem. Front Cell Infect Microbiol 4: 155.

194. IdroR, MarshK, JohnCC, NewtonCR (2010) Cerebral malaria: mechanisms of brain injury and strategies for improved neurocognitive outcome. Pediatr Res 68: 267–274.

195. ZhaoH, AoshiT, KawaiS, MoriY, KonishiA, et al. (2014) Olfactory plays a key role in spatiotemporal pathogenesis of cerebral malaria. Cell Host Microbe 15: 551–563.

196. SchmutzhardJ, KositzCH, LacknerP, PritzC, GlueckertR, et al. (2011) Murine cerebral malaria: histopathology and ICAM 1 immunohistochemistry of the inner ear. Trop Med Int Health 16: 914–922.

197. SchmutzhardJ, KositzCH, LacknerP, DietmannA, FischerM, et al. (2010) Murine malaria is associated with significant hearing impairment. Malar J 9: 159.

198. ZhaoSZ, MackenzieIJ (2011) Deafness: malaria as a forgotten cause. Ann Trop Paediatr 31: 1–10.

199. SagguR, FailleD, GrauGE, CozzonePJ, ViolaA (2011) In the Eye of Experimental Cerebral Malaria. Am J Pathol 179: 1104–1109.

200. BrewsterDR, KwiatkowskiD, WhiteNJ (1990) Neurological sequelae of cerebral malaria in children. Lancet 336: 1039–1043.

201. Dorovini-ZisK, SchmidtK, HuynhH, FuW, WhittenRO, et al. (2011) The neuropathology of fatal cerebral malaria in malawian children. Am J Pathol 178: 2146–2158.

202. MilnerDAJr, ValimC, CarrRA, ChandakPB, FosikoNG, et al. (2013) A histological method for quantifying Plasmodium falciparum in the brain in fatal paediatric cerebral malaria. Malar J 12: 191.

203. WhiteNJ, TurnerGD, DayNP, DondorpAM (2013) Lethal malaria: Marchiafava and Bignami were right. J Infect Dis 208: 192–198.

204. WHO (2011) World Malaria Report: 2011. Geneva, Switzerland: World Health Organization.

205. MohanA, SharmaSK, BollineniS (2008) Acute lung injury and acute respiratory distress syndrome in malaria. J Vector Borne Dis 45: 179–193.

206. AnsteyNM, JacupsSP, CainT, PearsonT, ZiesingPJ, et al. (2002) Pulmonary manifestations of uncomplicated falciparum and vivax malaria: cough, small airways obstruction, impaired gas transfer, and increased pulmonary phagocytic activity. J Infect Dis 185: 1326–1334.

207. MaguireGP, HandojoT, PainMC, KenangalemE, PriceRN, et al. (2005) Lung injury in uncomplicated and severe falciparum malaria: a longitudinal study in papua, Indonesia. J Infect Dis 192: 1966–1974.

208. SarkarD, RayS, SahaM, ChakrabortyA, TalukdarA (2013) Clinico-laboratory profile of severe Plasmodium vivax malaria in a tertiary care centre in Kolkata. Trop Parasitol 3: 53–57.

209. SarkarS, BhattacharyaP (2008) Cerebral malaria caused by Plasmodium vivax in adult subjects. Indian J Crit Care Med 12: 204–205.

210. BhattacharjeeP, DubeyS, GuptaVK, AgarwalP, MahatoMP (2013) The clinicopathologic manifestations of Plasmodium vivax malaria in children: a growing menace. J Clin Diagn Res 7: 861–867.

211. AbdallahTM, AbdeenMT, AhmedIS, HamdanHZ, MagzoubM, et al. (2013) Severe Plasmodium falciparum and Plasmodium vivax malaria among adults at Kassala Hospital, eastern Sudan. Malar J 12: 148.

212. GehlawatVK, AryaV, KaushikJS, GathwalaG (2013) Clinical spectrum and treatment outcome of severe malaria caused by Plasmodium vivax in 18 children from northern India. Pathog Glob Health 107: 210–214.

213. PinzonMA, PinedaJC, RossoF, ShinchiM, Bonilla-AbadiaF (2013) Plasmodium vivax cerebral malaria complicated with venous sinus thrombosis in Colombia. Asian Pac J Trop Med 6: 413–415.

214. BegMA, KhanR, BaigSM, GulzarZ, HussainR, et al. (2002) Cerebral involvement in benign tertian malaria. Am J Trop Med Hyg 67: 230–232.

215. ThapaR, PatraV, KunduR (2007) Plasmodium vivax cerebral malaria. Indian Pediatr 44: 433–434.

216. AndradeBB, Reis-FilhoA, Souza-NetoSM, ClarencioJ, CamargoLM, et al. (2010) Severe Plasmodium vivax malaria exhibits marked inflammatory imbalance. Malar J 9: 13.

217. CromerD, EvansKJ, SchofieldL, DavenportMP (2006) Preferential invasion of reticulocytes during late-stage Plasmodium berghei infection accounts for reduced circulating reticulocyte levels. Int J Parasitol 36: 1389–1397.

218. McNallyJ, O'DonovanSM, DaltonJP (1992) Plasmodium berghei and Plasmodium chabaudi chabaudi: development of simple in vitro erythrocyte invasion assays. Parasitology 105 (Pt 3) 355–362.

219. RussellB, SuwanaruskR, BorlonC, CostaFT, ChuCS, et al. (2011) A reliable ex vivo invasion assay of human reticulocytes by Plasmodium vivax. Blood 118: e74–81.

220. PanichakulT, SattabongkotJ, ChotivanichK, SirichaisinthopJ, CuiL, et al. (2007) Production of erythropoietic cells in vitro for continuous culture of Plasmodium vivax. Int J Parasitol 37: 1551–1557.

221. Vanderberg JP, Gwadz R (1980) The transmission by mosquitoes of Plasmodia in the laboratory. In: Kreier J, editor. Malaria: pathology, vector studies and culture. New York, N.Y.: Academic Press. pp. 154–218.

222. Franke-FayardB, TruemanH, RamesarJ, MendozaJ, van der KeurM, et al. (2004) A Plasmodium berghei reference line that constitutively expresses GFP at a high level throughout the complete life cycle. Mol Biochem Parasitol 137: 23–33.

223. YoeliM, HargreavesBJ (1974) Brain capillary blockage produced by a virulent strain of rodent malaria. Science 184: 572–573.

224. WeissL (1989) Mechanisms of splenic control of murine malaria: cellular reactions of the spleen in lethal (strain 17XL) Plasmodium yoelii malaria in BALB/c mice, and the consequences of pre-infective splenectomy. Am J Trop Med Hyg 41: 144–160.

225. YoeliM, HargreavesB, CarterR, WallikerD (1975) Sudden increase in virulence in a strain of Plasmodium berghei yoelii. Ann Trop Med Parasitol 69: 173–178.

226. KnopM, BarrF, RiedelCG, HeckelT, ReichelC (2002) Improved version of the red fluorescent protein (drFP583/DsRed/RFP). Biotechniques 33: 592–602.

227. MikolajczakSA, AlyAS, DumpitRF, VaughanAM, KappeSH (2008) An efficient strategy for gene targeting and phenotypic assessment in the Plasmodium yoelii rodent malaria model. Mol Biochem Parasitol 158: 213–216.

228. TarunAS, BaerK, DumpitRF, GrayS, LejarceguiN, et al. (2006) Quantitative isolation and in vivo imaging of malaria parasite liver stages. Int J Parasitol 36: 1283–1293.

229. NieCQ, BernardNJ, NormanMU, AmanteFH, LundieRJ, et al. (2009) IP-10-mediated T cell homing promotes cerebral inflammation over splenic immunity to malaria infection. PLoS Pathog 5: e1000369.

230. RestJR (1982) Cerebral malaria in inbred mice. I. A new model and its pathology. Trans Royal Soc Trop Med Hyg 76: 410–415.

231. Van den SteenPE, DeroostK, Van AelstI, GeurtsN, MartensE, et al. (2008) CXCR3 determines strain susceptibility to murine cerebral malaria by mediating T lymphocyte migration toward IFN-gamma-induced chemokines. Eur J Immunol 38: 1082–1095.

232. AmanteFH, StanleyAC, RandallLM, ZhouY, HaqueA, et al. (2007) A role for natural regulatory T cells in the pathogenesis of experimental cerebral malaria. Am J Pathol 171: 548–559.

233. GrauGE, HeremansH, PiguetPF, PointaireP, LambertPH, et al. (1989) Monoclonal antibody against interferon gamma can prevent experimental cerebral malaria and its associated overproduction of tumor necrosis factor. Proc Natl Acad Sci USA 86: 5572–5574.

234. GrauGE, PiguetPF, EngersHD, LouisJA, VassalliP, et al. (1986) L3T4+ T lymphocytes play a major role in the pathogenesis of murine cerebral malaria. J Immunol 137: 2348–2354.

235. HearnJ, RaymentN, LandonDN, KatzDR, de SouzaJB (2000) Immunopathology of cerebral malaria: morphological evidence of parasite sequestration in murine brain microvasculature. Infect Immun 68: 5364–5376.

236. JenningsVM, ActorJK, LalAA, HunterRL (1997) Cytokine profile suggesting that murine cerebral malaria is an encephalitis. Infect Immun 65: 4883–4887.

237. JenningsVM, LalAA, HunterRL (1998) Evidence for multiple pathologic and protective mechanisms of murine cerebral malaria. Infect Immun 66: 5972–5979.

238. KamiyamaT, TatsumiM, MatsubaraJ, YamamotoK, RubioZ, et al. (1987) Manifestation of cerebral malaria-like symptoms in the WM/Ms rat infected with Plasmodium berghei strain NK65. J Parasitol 73: 1138–1145.

239. Lacerda-QueirozN, RodriguesDH, VilelaMC, MirandaASd, AmaralDCG, et al. (2010) Inflammatory changes in the central nervous system are associated with behavioral impairment in Plasmodium berghei (strain ANKA)-infected mice. Exp Parasitol 125: 271–278.

240. MackeyLJ, HochmannA, JuneCH, ContrerasCE, LambertPH (1980) Immunopathological aspects of Plasmodium berghei infection in five strains of mice. II. Immunopathology of cerebral and other tissue lesions during the infection. Clin Exp Immunol 42: 412–420.

241. PatelSN, BerghoutJ, LovegroveFE, AyiK, ConroyA, et al. (2008) C5 deficiency and C5a or C5aR blockade protects against cerebral malaria. J Exp Med 205: 1133–1143.

242. YanezDM, ManningDD, CooleyAJ, WeidanzWP, van der HeydeHC (1996) Participation of lymphocyte subpopulations in the pathogenesis of experimental murine cerebral malaria. J Immunol 157: 1620–1624.

243. PolderTW, JerusalemCR, ElingWMC (1991) Morphological characteristics of intracerebral arterioles in clinical (Plasmodium falciparum) and experimental (Plasmodium berghei) cerebral malaria. J Neurol Sci 101: 35–46.

244. McElroyPD, BeierJC, OsterCN, OnyangoFK, OlooAJ, et al. (1997) Dose- and time-dependent relations between infective Anopheles inoculation and outcomes of Plasmodium falciparum parasitemia among children in western Kenya. Am J Epidemiol 145: 945–956.

245. HatcherJP, JonesDN, RogersDC, HatcherPD, ReavillC, et al. (2001) Development of SHIRPA to characterise the phenotype of gene-targeted mice. Behav Brain Res 125: 43–47.

246. CarrollRW, WainwrightMS, KimKY, KidambiT, GomezND, et al. (2010) A rapid murine coma and behavior scale for quantitative assessment of murine cerebral malaria. PLoS ONE 5 e13124.

247. FrevertU, EngelmannS, ZougbédéS, StangeJ, NgB, et al. (2005) Intravital observation of Plasmodium berghei sporozoite infection of the liver. PLoS Biol 3: e192.

248. BaerK, KlotzC, KappeSH, SchniederT, FrevertU (2007) Release of hepatic Plasmodium yoelii merozoites into the pulmonary microvasculature. PLoS Pathog 3: e171.

249. BeckerMD, NobilingR, PlanckSR, RosenbaumJT (2000) Digital video-imaging of leukocyte migration in the iris: intravital microscopy in a physiological model during the onset of endotoxin-induced uveitis. J Immunol Methods 240: 23–37.

250. CabreraM, PeweLL, HartyJT, FrevertU (2013) In vivo CD8+ T cell dynamics in the liver of Plasmodium yoelii immunized and infected mice. PLoS One 8: e70842.

251. GundraUM, MishraBB, WongK, TealeJM (2011) Increased disease severity of parasite-infected TLR2-/- mice is correlated with decreased central nervous system inflammation and reduced numbers of cells with alternatively activated macrophage phenotypes in a murine model of neurocysticercosis. Infect Immun 79: 2586–2596.

252. IraniDN, GriffinDE (1991) Isolation of brain parenchymal lymphocytes for flow cytometric analysis. Application to acute viral encephalitis. J Immunol Methods 139: 223–231.

253. MishraBB, GundraUM, WongK, TealeJM (2009) MyD88-deficient mice exhibit decreased parasite-induced immune responses but reduced disease severity in a murine model of neurocysticercosis. Infect Immun 77: 5369–5379.

254. CabreraM, FrevertU (2012) Novel in vivo imaging techniques for the liver microvasculature. IntraVital 1: 107–114.

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