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Special Focus Review

Contrasting pediatric and adult cerebral malaria

The role of the endothelial barrier

, , &
Pages 543-555 | Received 19 May 2013, Accepted 29 Jul 2013, Published online: 02 Aug 2013

References

  • World Malaria Report WHO.. . 2012.
  • Zlokovic BV. The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron 2008; 57:178 - 201; http://dx.doi.org/10.1016/j.neuron.2008.01.003; PMID: 18215617
  • McAdams RM, Juul SE. The role of cytokines and inflammatory cells in perinatal brain injury. Neurol Res Int 2012; 2012:561494; http://dx.doi.org/10.1155/2012/561494; PMID: 22530124
  • Kacem K, Lacombe P, Seylaz J, Bonvento G. Structural organization of the perivascular astrocyte endfeet and their relationship with the endothelial glucose transporter: a confocal microscopy study. Glia 1998; 23:1 - 10; http://dx.doi.org/10.1002/(SICI)1098-1136(199805)23:1<1::AID-GLIA1>3.0.CO;2-B; PMID: 9562180
  • Engelhardt B, Sorokin L. The blood-brain and the blood-cerebrospinal fluid barriers: function and dysfunction. Semin Immunopathol 2009; 31:497 - 511; http://dx.doi.org/10.1007/s00281-009-0177-0; PMID: 19779720
  • Khalil M, Ronda J, Weintraub M, Jain K, Silver R, Silverman AJ. Brain mast cell relationship to neurovasculature during development. Brain Res 2007; 1171:18 - 29; http://dx.doi.org/10.1016/j.brainres.2007.07.034; PMID: 17764664
  • Owens T, Bechmann I, Engelhardt B. Perivascular spaces and the two steps to neuroinflammation. J Neuropathol Exp Neurol 2008; 67:1113 - 21; http://dx.doi.org/10.1097/NEN.0b013e31818f9ca8; PMID: 19018243
  • MacPherson GG, Warrell MJ, White NJ, Looareesuwan S, Warrell DA. Human cerebral malaria. A quantitative ultrastructural analysis of parasitized erythrocyte sequestration. Am J Pathol 1985; 119:385 - 401; PMID: 3893148
  • 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; http://dx.doi.org/10.1371/journal.ppat.1002982; PMID: 23133375
  • Muldoon LL, Alvarez JI, Begley DJ, Boado RJ, Del Zoppo GJ, Doolittle ND, et al. Immunologic privilege in the central nervous system and the blood-brain barrier. J Cereb Blood Flow Metab 2013; 33:13 - 21; http://dx.doi.org/10.1038/jcbfm.2012.153; PMID: 23072749
  • Abbott NJ. Astrocyte-endothelial interactions and blood-brain barrier permeability. J Anat 2002; 200:629 - 38; http://dx.doi.org/10.1046/j.1469-7580.2002.00064.x; PMID: 12162730
  • Hirase T, Staddon JM, Saitou M, Ando-Akatsuka Y, Itoh M, Furuse M, et al. Occludin as a possible determinant of tight junction permeability in endothelial cells. J Cell Sci 1997; 110:1603 - 13; PMID: 9247194
  • Piontek J, Winkler L, Wolburg H, Müller SL, Zuleger N, Piehl C, et al. Formation of tight junction: determinants of homophilic interaction between classic claudins. FASEB J 2008; 22:146 - 58; http://dx.doi.org/10.1096/fj.07-8319com; PMID: 17761522
  • Nitta T, Hata M, Gotoh S, Seo Y, Sasaki H, Hashimoto N, et al. Size-selective loosening of the blood-brain barrier in claudin-5-deficient mice. J Cell Biol 2003; 161:653 - 60; http://dx.doi.org/10.1083/jcb.200302070; PMID: 12743111
  • Daneman R, Zhou L, Kebede AA, Barres BA. Pericytes are required for blood-brain barrier integrity during embryogenesis. Nature 2010; 468:562 - 6; http://dx.doi.org/10.1038/nature09513; PMID: 20944625
  • Abbott NJ, Rönnbäck L, Hansson E. Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci 2006; 7:41 - 53; http://dx.doi.org/10.1038/nrn1824; PMID: 16371949
  • Gavard J, Patel V, Gutkind JS. Angiopoietin-1 prevents VEGF-induced endothelial permeability by sequestering Src through mDia. Dev Cell 2008; 14:25 - 36; http://dx.doi.org/10.1016/j.devcel.2007.10.019; PMID: 18194650
  • Finney CA, Hawkes CA, Kain DC, Dhabangi A, Musoke C, Cserti-Gazdewich C, et al. S1P is associated with protection in human and experimental cerebral malaria. Mol Med 2011; 17:717 - 25; http://dx.doi.org/10.2119/molmed.2010.00214; PMID: 21556483
  • London NR, Zhu W, Bozza FA, Smith MC, Greif DM, Sorensen LK, et al. Targeting Robo4-dependent Slit signaling to survive the cytokine storm in sepsis and influenza. Sci Transl Med 2010; 2:23ra19; http://dx.doi.org/10.1126/scitranslmed.3000678; PMID: 20375003
  • Serghides L, Kim H, Lu Z, Kain DC, Miller C, Francis RC, et al. Inhaled nitric oxide reduces endothelial activation and parasite accumulation in the brain, and enhances survival in experimental cerebral malaria. PLoS One 2011; 6:e27714; http://dx.doi.org/10.1371/journal.pone.0027714; PMID: 22110737
  • Erdman LK, Dhabangi A, Musoke C, Conroy AL, Hawkes M, Higgins S, et al. Combinations of host biomarkers predict mortality among Ugandan children with severe malaria: a retrospective case-control study. PLoS One 2011; 6:e17440; http://dx.doi.org/10.1371/journal.pone.0017440; PMID: 21364762
  • Conroy AL, Phiri H, Hawkes M, Glover S, Mallewa M, Seydel KB, et al. Endothelium-based biomarkers are associated with cerebral malaria in Malawian children: a retrospective case-control study. PLoS One 2010; 5:e15291; http://dx.doi.org/10.1371/journal.pone.0015291; PMID: 21209923
  • Conroy AL, Lafferty EI, Lovegrove FE, Krudsood S, Tangpukdee N, Liles WC, et al. Whole blood angiopoietin-1 and -2 levels discriminate cerebral and severe (non-cerebral) malaria from uncomplicated malaria. Malar J 2009; 8:295; http://dx.doi.org/10.1186/1475-2875-8-295; PMID: 20003529
  • Jain V, Lucchi NW, Wilson NO, Blackstock AJ, Nagpal AC, Joel PK, et al. Plasma levels of angiopoietin-1 and -2 predict cerebral malaria outcome in Central India. Malar J 2011; 10:383; http://dx.doi.org/10.1186/1475-2875-10-383; PMID: 22192385
  • Lovegrove FE, Tangpukdee N, Opoka RO, Lafferty EI, Rajwans N, Hawkes M, et al. Serum angiopoietin-1 and -2 levels discriminate cerebral malaria from uncomplicated malaria and predict clinical outcome in African children. PLoS One 2009; 4:e4912; http://dx.doi.org/10.1371/journal.pone.0004912; PMID: 19300530
  • Conroy AL, Glover SJ, Hawkes M, Erdman LK, Seydel KB, Taylor TE, et al. Angiopoietin-2 levels are associated with retinopathy and predict mortality in Malawian children with cerebral malaria: a retrospective case-control study*. Crit Care Med 2012; 40:952 - 9; http://dx.doi.org/10.1097/CCM.0b013e3182373157; PMID: 22343839
  • Rondaij MG, Bierings R, Kragt A, van Mourik JA, Voorberg J. Dynamics and plasticity of Weibel-Palade bodies in endothelial cells. Arterioscler Thromb Vasc Biol 2006; 26:1002 - 7; http://dx.doi.org/10.1161/01.ATV.0000209501.56852.6c; PMID: 16469951
  • Fiedler U, Reiss Y, Scharpfenecker M, Grunow V, Koidl S, Thurston G, et al. Angiopoietin-2 sensitizes endothelial cells to TNF-alpha and has a crucial role in the induction of inflammation. Nat Med 2006; 12:235 - 9; http://dx.doi.org/10.1038/nm1351; PMID: 16462802
  • Yeo TW, Lampah DA, Gitawati R, Tjitra E, Kenangalem E, Piera K, et al. Angiopoietin-2 is associated with decreased endothelial nitric oxide and poor clinical outcome in severe falciparum malaria. Proc Natl Acad Sci U S A 2008; 105:17097 - 102; http://dx.doi.org/10.1073/pnas.0805782105; PMID: 18957536
  • Conroy ALS, Zhong KL, Rennie K, Ward M, Sarma P, Molyneux JV, et al. Complement activation and the resulting placental vascular insufficiency drives fetal growth restriction associated with placental malaria. Cell Host Microbe 2013; 13:215 - 26; http://dx.doi.org/10.1016/j.chom.2013.01.010; PMID: 23414761
  • Prapansilp P, Medana I, Mai NT, Day NP, Phu NH, Yeo TW, et al. A clinicopathological correlation of the expression of the angiopoietin-Tie-2 receptor pathway in the brain of adults with Plasmodium falciparum malaria. Malar J 2013; 12:50; http://dx.doi.org/10.1186/1475-2875-12-50; PMID: 23383853
  • Pieh C, Agostini H, Buschbeck C, Krüger M, Schulte-Mönting J, Zirrgiebel U, et al. VEGF-A, VEGFR-1, VEGFR-2 and Tie2 levels in plasma of premature infants: relationship to retinopathy of prematurity. Br J Ophthalmol 2008; 92:689 - 93; http://dx.doi.org/10.1136/bjo.2007.128371; PMID: 18408080
  • Steinle JJ, Sharma S, Chin VC. Normal aging involves altered expression of growth factors in the rat choroid. J Gerontol A Biol Sci Med Sci 2008; 63:135 - 40; http://dx.doi.org/10.1093/gerona/63.2.135; PMID: 18314447
  • Matsushita K, Morrell CN, Cambien B, Yang SX, Yamakuchi M, Bao C, et al. Nitric oxide regulates exocytosis by S-nitrosylation of N-ethylmaleimide-sensitive factor. Cell 2003; 115:139 - 50; http://dx.doi.org/10.1016/S0092-8674(03)00803-1; PMID: 14567912
  • Yeo TW, Lampah DA, Tjitra E, Gitawati R, Kenangalem E, Piera K, et al. Relationship of cell-free hemoglobin to impaired endothelial nitric oxide bioavailability and perfusion in severe falciparum malaria. J Infect Dis 2009; 200:1522 - 9; http://dx.doi.org/10.1086/644641; PMID: 19803726
  • Gramaglia I, Sobolewski P, Meays D, Contreras R, Nolan JP, Frangos JA, et al. Low nitric oxide bioavailability contributes to the genesis of experimental cerebral malaria. Nat Med 2006; 12:1417 - 22; http://dx.doi.org/10.1038/nm1499; PMID: 17099710
  • Yeo TW, Lampah DA, Gitawati R, Tjitra E, Kenangalem E, McNeil YR, et al. Impaired nitric oxide bioavailability and L-arginine reversible endothelial dysfunction in adults with falciparum malaria. J Exp Med 2007; 204:2693 - 704; http://dx.doi.org/10.1084/jem.20070819; PMID: 17954570
  • Serirom S, Raharjo WH, Chotivanich K, Loareesuwan S, Kubes P, Ho M. Anti-adhesive effect of nitric oxide on Plasmodium falciparum cytoadherence under flow. Am J Pathol 2003; 162:1651 - 60; http://dx.doi.org/10.1016/S0002-9440(10)64299-X; PMID: 12707049
  • Smith AR, Visioli F, Frei B, Hagen TM. Age-related changes in endothelial nitric oxide synthase phosphorylation and nitric oxide dependent vasodilation: evidence for a novel mechanism involving sphingomyelinase and ceramide-activated phosphatase 2A. Aging Cell 2006; 5:391 - 400; http://dx.doi.org/10.1111/j.1474-9726.2006.00232.x; PMID: 16930126
  • Lee JF, Zeng Q, Ozaki H, Wang L, Hand AR, Hla T, et al. Dual roles of tight junction-associated protein, zonula occludens-1, in sphingosine 1-phosphate-mediated endothelial chemotaxis and barrier integrity. J Biol Chem 2006; 281:29190 - 200; http://dx.doi.org/10.1074/jbc.M604310200; PMID: 16891661
  • Coelho RP, Saini HS, Sato-Bigbee C. Sphingosine-1-phosphate and oligodendrocytes: from cell development to the treatment of multiple sclerosis. Prostaglandins Other Lipid Mediat 2010; 91:139 - 44; http://dx.doi.org/10.1016/j.prostaglandins.2009.04.002; PMID: 19808013
  • Brose K, Bland KS, Wang KH, Arnott D, Henzel W, Goodman CS, et al. Slit proteins bind Robo receptors and have an evolutionarily conserved role in repulsive axon guidance. Cell 1999; 96:795 - 806; http://dx.doi.org/10.1016/S0092-8674(00)80590-5; PMID: 10102268
  • Stiles J, Jernigan TL. The basics of brain development. Neuropsychol Rev 2010; 20:327 - 48; http://dx.doi.org/10.1007/s11065-010-9148-4; PMID: 21042938
  • Saunders NR, Liddelow SA, Dziegielewska KM. Barrier mechanisms in the developing brain. Front Pharmacol 2012; 3:46; http://dx.doi.org/10.3389/fphar.2012.00046; PMID: 22479246
  • Reiss AL, Abrams MT, Singer HS, Ross JL, Denckla MB. Brain development, gender and IQ in children. A volumetric imaging study. Brain 1996; 119:1763 - 74; http://dx.doi.org/10.1093/brain/119.5.1763; PMID: 8931596
  • Rice D, Barone S Jr.. Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. Environ Health Perspect 2000; 108:Suppl 3 511 - 33; PMID: 10852851
  • Gupta RK, Kanungo M. Glial molecular alterations with mouse brain development and aging: up-regulation of the Kir4.1 and aquaporin-4. Age (Dordr) 2013; 35:59 - 67; http://dx.doi.org/10.1007/s11357-011-9330-5; PMID: 22057895
  • Sofroniew MV. Reactive astrocytes in neural repair and protection. Neuroscientist 2005; 11:400 - 7; http://dx.doi.org/10.1177/1073858405278321; PMID: 16151042
  • Birbeck GL, Molyneux ME, Kaplan PW, Seydel KB, Chimalizeni YF, Kawaza K, et al. Blantyre Malaria Project Epilepsy Study (BMPES) of neurological outcomes in retinopathy-positive paediatric cerebral malaria survivors: a prospective cohort study. Lancet Neurol 2010; 9:1173 - 81; http://dx.doi.org/10.1016/S1474-4422(10)70270-2; PMID: 21056005
  • Boivin MJ, Gladstone MJ, Vokhiwa M, Birbeck GL, Magen JG, Page C, et al. Developmental outcomes in Malawian children with retinopathy-positive cerebral malaria. Trop Med Int Health 2011; 16:263 - 71; http://dx.doi.org/10.1111/j.1365-3156.2010.02704.x; PMID: 21143354
  • Zecevic N, Bourgeois JP, Rakic P. Changes in synaptic density in motor cortex of rhesus monkey during fetal and postnatal life. Brain Res Dev Brain Res 1989; 50:11 - 32; http://dx.doi.org/10.1016/0165-3806(89)90124-7; PMID: 2582602
  • Innocenti GM, Price DJ. Exuberance in the development of cortical networks. Nat Rev Neurosci 2005; 6:955 - 65; http://dx.doi.org/10.1038/nrn1790; PMID: 16288299
  • Huttenlocher PR, Dabholkar AS. Regional differences in synaptogenesis in human cerebral cortex. J Comp Neurol 1997; 387:167 - 78; http://dx.doi.org/10.1002/(SICI)1096-9861(19971020)387:2<167::AID-CNE1>3.0.CO;2-Z; PMID: 9336221
  • McDonald CR, Elphinstone RE, Kain KC. The impact of placental malaria on neurodevelopment of exposed infants: a role for the complement system?. Trends Parasitol 2013; 29:213 - 9; http://dx.doi.org/10.1016/j.pt.2013.03.005; PMID: 23562777
  • Chapman SB, Max JE, Gamino JF, McGlothlin JH, Cliff SN. Discourse plasticity in children after stroke: age at injury and lesion effects. Pediatr Neurol 2003; 29:34 - 41; http://dx.doi.org/10.1016/S0887-8994(03)00012-2; PMID: 13679119
  • Durkin MS, Olsen S, Barlow B, Virella A, Connolly ES Jr.. The epidemiology of urban pediatric neurological trauma: evaluation of, and implications for, injury prevention programs. Neurosurgery 1998; 42:300 - 10; http://dx.doi.org/10.1097/00006123-199802000-00052; PMID: 9482180
  • Fernández-López D, Faustino J, Daneman R, Zhou L, Lee SY, Derugin N, et al. Blood-brain barrier permeability is increased after acute adult stroke but not neonatal stroke in the rat. J Neurosci 2012; 32:9588 - 600; http://dx.doi.org/10.1523/JNEUROSCI.5977-11.2012; PMID: 22787045
  • Claus CP, Tsuru-Aoyagi K, Adwanikar H, Walker B, Manvelyan H, Whetstone W, et al. Age is a determinant of leukocyte infiltration and loss of cortical volume after traumatic brain injury. Dev Neurosci 2010; 32:454 - 65; PMID: 20847543
  • Holtzman D, DeVries C, Nguyen H, Olson J, Bensch K. Maturation of resistance to lead encephalopathy: cellular and subcellular mechanisms. Neurotoxicology 1984; 5:97 - 124; PMID: 6542983
  • Lawson LJ, Perry VH. The unique characteristics of inflammatory responses in mouse brain are acquired during postnatal development. Eur J Neurosci 1995; 7:1584 - 95; http://dx.doi.org/10.1111/j.1460-9568.1995.tb01154.x; PMID: 7551185
  • Anthony DC, Bolton SJ, Fearn S, Perry VH. Age-related effects of interleukin-1 beta on polymorphonuclear neutrophil-dependent increases in blood-brain barrier permeability in rats. Brain 1997; 120:435 - 44; http://dx.doi.org/10.1093/brain/120.3.435; PMID: 9126055
  • Anthony D, Dempster R, Fearn S, Clements J, Wells G, Perry VH, et al. CXC chemokines generate age-related increases in neutrophil-mediated brain inflammation and blood-brain barrier breakdown. Curr Biol 1998; 8:923 - 6; http://dx.doi.org/10.1016/S0960-9822(07)00373-9; PMID: 9707404
  • Stolp HB, Dziegielewska KM, Ek CJ, Habgood MD, Lane MA, Potter AM, et al. Breakdown of the blood-brain barrier to proteins in white matter of the developing brain following systemic inflammation. Cell Tissue Res 2005; 320:369 - 78; http://dx.doi.org/10.1007/s00441-005-1088-6; PMID: 15846513
  • van der Heyde HC, Nolan J, Combes V, Gramaglia I, Grau GE. A unified hypothesis for the genesis of cerebral malaria: sequestration, inflammation and hemostasis leading to microcirculatory dysfunction. Trends Parasitol 2006; 22:503 - 8; http://dx.doi.org/10.1016/j.pt.2006.09.002; PMID: 16979941
  • Mita-Mendoza NK, van de Hoef DL, Lopera-Mesa TM, Doumbia S, Konate D, Doumbouya M, et al. A potential role for plasma uric acid in the endothelial pathology of Plasmodium falciparum malaria. PLoS One 2013; 8:e54481; http://dx.doi.org/10.1371/journal.pone.0054481; PMID: 23349902
  • Gillrie MR, Lee K, Gowda DC, Davis SP, Monestier M, Cui L, et al. Plasmodium falciparum histones induce endothelial proinflammatory response and barrier dysfunction. Am J Pathol 2012; 180:1028 - 39; http://dx.doi.org/10.1016/j.ajpath.2011.11.037; PMID: 22260922
  • Lacerda-Queiroz N, Rodrigues DH, Vilela MC, Rachid MA, Soriani FM, Sousa LP, et al. Platelet-activating factor receptor is essential for the development of experimental cerebral malaria. Am J Pathol 2012; 180:246 - 55; http://dx.doi.org/10.1016/j.ajpath.2011.09.038; PMID: 22079430
  • Zougbédé S, Miller F, Ravassard P, Rebollo A, Cicéron L, Couraud PO, et al. Metabolic acidosis induced by Plasmodium falciparum intraerythrocytic stages alters blood-brain barrier integrity. J Cereb Blood Flow Metab 2011; 31:514 - 26; http://dx.doi.org/10.1038/jcbfm.2010.121; PMID: 20683453
  • Souza MC, Paixão FH, Ferraris FK, Ribeiro I, Henriques Md. Artesunate Exerts a Direct Effect on Endothelial Cell Activation and NF-κB Translocation in a Mechanism Independent of Plasmodium Killing. Malar Res Treat 2012; 2012:679090; http://dx.doi.org/10.1155/2012/679090; PMID: 23097741
  • Gray C, McCormick C, Turner G, Craig A. ICAM-1 can play a major role in mediating P. falciparum adhesion to endothelium under flow. Mol Biochem Parasitol 2003; 128:187 - 93; http://dx.doi.org/10.1016/S0166-6851(03)00075-6; PMID: 12742585
  • Taylor TE, Fu WJ, Carr RA, Whitten RO, Mueller JS, Fosiko NG, et al. Differentiating the pathologies of cerebral malaria by postmortem parasite counts. Nat Med 2004; 10:143 - 5; http://dx.doi.org/10.1038/nm986; PMID: 14745442
  • Dorovini-Zis K, Schmidt K, Huynh H, Fu W, Whitten RO, Milner D, et al. The neuropathology of fatal cerebral malaria in malawian children. Am J Pathol 2011; 178:2146 - 58; http://dx.doi.org/10.1016/j.ajpath.2011.01.016; PMID: 21514429
  • Lee WH, Sonntag WE, Lee YW. Aging attenuates radiation-induced expression of pro-inflammatory mediators in rat brain. Neurosci Lett 2010; 476:89 - 93; http://dx.doi.org/10.1016/j.neulet.2010.04.009; PMID: 20385203
  • Hobden JA, Masinick SA, Barrett RP, Hazlett LD. Aged mice fail to upregulate ICAM-1 after Pseudomonas aeruginosa corneal infection. Invest Ophthalmol Vis Sci 1995; 36:1107 - 14; PMID: 7730020
  • Xu YZ, Nygård M, Kristensson K, Bentivoglio M. Regulation of cytokine signaling and T-cell recruitment in the aging mouse brain in response to central inflammatory challenge. Brain Behav Immun 2010; 24:138 - 52; http://dx.doi.org/10.1016/j.bbi.2009.09.006; PMID: 19765643
  • Reis PA, Estato V, da Silva TI, d’Avila JC, Siqueira LD, Assis EF, et al. Statins decrease neuroinflammation and prevent cognitive impairment after cerebral malaria. PLoS Pathog 2012; 8:e1003099; http://dx.doi.org/10.1371/journal.ppat.1003099; PMID: 23300448
  • Elias RM, Correa-Costa M, Barreto CR, Silva RC, Hayashida CY, Castoldi A, et al. Oxidative stress and modification of renal vascular permeability are associated with acute kidney injury during P. berghei ANKA infection. PLoS One 2012; 7:e44004; http://dx.doi.org/10.1371/journal.pone.0044004; PMID: 22952850
  • Lacerda-Queiroz N, Lima OC, Carneiro CM, Vilela MC, Teixeira AL, Teixeira-Carvalho A, et al. Plasmodium berghei NK65 induces cerebral leukocyte recruitment in vivo: an intravital microscopic study. Acta Trop 2011; 120:31 - 9; http://dx.doi.org/10.1016/j.actatropica.2011.04.020; PMID: 21722620
  • Lacerda-Queiroz N, Rachid MA, Teixeira MM, Teixeira AL. The role of platelet-activating factor receptor (PAFR) in lung pathology during experimental malaria. Int J Parasitol 2013; 43:11 - 5; http://dx.doi.org/10.1016/j.ijpara.2012.11.008; PMID: 23260771
  • Epiphanio S, Campos MG, Pamplona A, Carapau D, Pena AC, Ataíde R, et al. VEGF promotes malaria-associated acute lung injury in mice. PLoS Pathog 2010; 6:e1000916; http://dx.doi.org/10.1371/journal.ppat.1000916; PMID: 20502682
  • Susomboon P, Maneerat Y, Dekumyoy P, Kalambaheti T, Iwagami M, Komaki-Yasuda K, et al. Down-regulation of tight junction mRNAs in human endothelial cells co-cultured with Plasmodium falciparum-infected erythrocytes. Parasitol Int 2006; 55:107 - 12; http://dx.doi.org/10.1016/j.parint.2005.11.054; PMID: 16388977
  • Tripathi AK, Sullivan DJ, Stins MF. Plasmodium falciparum-infected erythrocytes decrease the integrity of human blood-brain barrier endothelial cell monolayers. J Infect Dis 2007; 195:942 - 50; http://dx.doi.org/10.1086/512083; PMID: 17330783
  • Brown H, Rogerson S, Taylor T, Tembo M, Mwenechanya J, Molyneux M, et al. Blood-brain barrier function in cerebral malaria in Malawian children. Am J Trop Med Hyg 2001; 64:207 - 13; PMID: 11442219
  • Brown H, Turner G, Rogerson S, Tembo M, Mwenechanya J, Molyneux M, et al. Cytokine expression in the brain in human cerebral malaria. J Infect Dis 1999; 180:1742 - 6; http://dx.doi.org/10.1086/315078; PMID: 10515846
  • Mooradian AD, Haas MJ, Chehade JM. Age-related changes in rat cerebral occludin and zonula occludens-1 (ZO-1). Mech Ageing Dev 2003; 124:143 - 6; http://dx.doi.org/10.1016/S0047-6374(02)00041-6; PMID: 12633933
  • D’Alessandro S, Basilico N, Prato M. Effects of Plasmodium falciparum-infected erythrocytes on matrix metalloproteinase-9 regulation in human microvascular endothelial cells. Asian Pac J Trop Med 2013; 6:195 - 9; http://dx.doi.org/10.1016/S1995-7645(13)60022-X; PMID: 23375032
  • Chen F, Ohashi N, Li W, Eckman C, Nguyen JH. Disruptions of occludin and claudin-5 in brain endothelial cells in vitro and in brains of mice with acute liver failure. Hepatology 2009; 50:1914 - 23; http://dx.doi.org/10.1002/hep.23203; PMID: 19821483
  • Yu TY, Pang JH, Wu KP, Chen MJ, Chen CH, Tsai WC. Aging is associated with increased activities of matrix metalloproteinase-2 and -9 in tenocytes. BMC Musculoskelet Disord 2013; 14:2; http://dx.doi.org/10.1186/1471-2474-14-2; PMID: 23281803
  • Pamplona A, Ferreira A, Balla J, Jeney V, Balla G, Epiphanio S, et al. Heme oxygenase-1 and carbon monoxide suppress the pathogenesis of experimental cerebral malaria. Nat Med 2007; 13:703 - 10; http://dx.doi.org/10.1038/nm1586; PMID: 17496899
  • Seixas E, Gozzelino R, Chora A, Ferreira A, Silva G, Larsen R, et al. Heme oxygenase-1 affords protection against noncerebral forms of severe malaria. Proc Natl Acad Sci U S A 2009; 106:15837 - 42; http://dx.doi.org/10.1073/pnas.0903419106; PMID: 19706490
  • Lin T, Kwak YH, Sammy F, He P, Thundivalappil S, Sun G, et al. Synergistic inflammation is induced by blood degradation products with microbial Toll-like receptor agonists and is blocked by hemopexin. J Infect Dis 2010; 202:624 - 32; http://dx.doi.org/10.1086/654929; PMID: 20617898
  • Balla J, Jacob HS, Balla G, Nath K, Eaton JW, Vercellotti GM. Endothelial-cell heme uptake from heme proteins: induction of sensitization and desensitization to oxidant damage. Proc Natl Acad Sci U S A 1993; 90:9285 - 9; http://dx.doi.org/10.1073/pnas.90.20.9285; PMID: 8415693
  • Jeney V, Balla J, Yachie A, Varga Z, Vercellotti GM, Eaton JW, et al. Pro-oxidant and cytotoxic effects of circulating heme. Blood 2002; 100:879 - 87; http://dx.doi.org/10.1182/blood.V100.3.879; PMID: 12130498
  • Motterlini R, Foresti R, Intaglietta M, Winslow RM. NO-mediated activation of heme oxygenase: endogenous cytoprotection against oxidative stress to endothelium. Am J Physiol 1996; 270:H107 - 14; PMID: 8769740
  • Di Giulio C, Verratti V, Artese L, Petruccelli G, Walski M, Pokorski M. Aging and expression of heme oxygenase-1 and endothelin-1 in the rat carotid body after chronic hypoxia. J Physiol Pharmacol 2009; 60:Suppl 5 41 - 4; PMID: 20134037
  • Kang MJ, Kim HJ, Kim HK, Lee JY, Kim DH, Jung KJ, et al. The effect of age and calorie restriction on HIF-1-responsive genes in aged liver. Biogerontology 2005; 6:27 - 37; http://dx.doi.org/10.1007/s10522-004-7381-z; PMID: 15834661
  • Tripathi AK, Sha W, Shulaev V, Stins MF, Sullivan DJ Jr.. Plasmodium falciparum-infected erythrocytes induce NF-kappaB regulated inflammatory pathways in human cerebral endothelium. Blood 2009; 114:4243 - 52; http://dx.doi.org/10.1182/blood-2009-06-226415; PMID: 19713460
  • Pino P, Vouldoukis I, Kolb JP, Mahmoudi N, Desportes-Livage I, Bricaire F, et al. Plasmodium falciparum--infected erythrocyte adhesion induces caspase activation and apoptosis in human endothelial cells. J Infect Dis 2003; 187:1283 - 90; http://dx.doi.org/10.1086/373992; PMID: 12696008
  • Taoufiq Z, Pino P, N’dilimabaka N, Arrouss I, Assi S, Soubrier F, et al. Atorvastatin prevents Plasmodium falciparum cytoadherence and endothelial damage. Malar J 2011; 10:52; http://dx.doi.org/10.1186/1475-2875-10-52; PMID: 21356073
  • Souraud JB, Briolant S, Dormoi J, Mosnier J, Savini H, Baret E, et al. Atorvastatin treatment is effective when used in combination with mefloquine in an experimental cerebral malaria murine model. Malar J 2012; 11:13; http://dx.doi.org/10.1186/1475-2875-11-13; PMID: 22233563
  • Hemmer CJ, Löbermann M, Unverricht M, Vogt A, Krause R, Reisinger EC. Activated protein C protects vascular endothelial cells from apoptosis in malaria and in sepsis. Trop Med Int Health 2011; 16:906 - 13; http://dx.doi.org/10.1111/j.1365-3156.2011.02788.x; PMID: 21615630
  • Dondorp A, Nosten F, Stepniewska K, Day N, White N, South East Asian Quinine Artesunate Malaria Trial (SEAQUAMAT) group. Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial. Lancet 2005; 366:717 - 25; http://dx.doi.org/10.1016/S0140-6736(05)67176-0; PMID: 16125588
  • Dondorp AM, Fanello CI, Hendriksen IC, Gomes E, Seni A, Chhaganlal KD, et al, AQUAMAT group. Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial. Lancet 2010; 376:1647 - 57; http://dx.doi.org/10.1016/S0140-6736(10)61924-1; PMID: 21062666
  • Dondorp AM, Lee SJ, Faiz MA, Mishra S, Price R, Tjitra E, et al. The relationship between age and the manifestations of and mortality associated with severe malaria. Clin Infect Dis 2008; 47:151 - 7; http://dx.doi.org/10.1086/589287; PMID: 18533842
  • Murray CJ, Rosenfeld LC, Lim SS, Andrews KG, Foreman KJ, Haring D, et al. Global malaria mortality between 1980 and 2010: a systematic analysis. Lancet 2012; 379:413 - 31; http://dx.doi.org/10.1016/S0140-6736(12)60034-8; PMID: 22305225
  • Kampondeni SD, Potchen MJ, Beare NA, Seydel KB, Glover SJ, Taylor TE, et al. MRI findings in a cohort of brain injured survivors of pediatric cerebral malaria. Am J Trop Med Hyg 2013; 88:542 - 6; http://dx.doi.org/10.4269/ajtmh.12-0538; PMID: 23339204
  • Boivin MJ. Effects of early cerebral malaria on cognitive ability in Senegalese children. J Dev Behav Pediatr 2002; 23:353 - 64; http://dx.doi.org/10.1097/00004703-200210000-00010; PMID: 12394524
  • Carter JA, Neville BG, Newton CR. Neuro-cognitive impairment following acquired central nervous system infections in childhood: a systematic review. Brain Res Brain Res Rev 2003; 43:57 - 69; http://dx.doi.org/10.1016/S0165-0173(03)00192-9; PMID: 14499462
  • Carter JA, Ross AJ, Neville BG, Obiero E, Katana K, Mung’ala-Odera V, et al. Developmental impairments following severe falciparum malaria in children. Trop Med Int Health 2005; 10:3 - 10; http://dx.doi.org/10.1111/j.1365-3156.2004.01345.x; PMID: 15655008
  • Carter JA, Mung’ala-Odera V, Neville BG, Murira G, Mturi N, Musumba C, et al. Persistent neurocognitive impairments associated with severe falciparum malaria in Kenyan children. J Neurol Neurosurg Psychiatry 2005; 76:476 - 81; http://dx.doi.org/10.1136/jnnp.2004.043893; PMID: 15774431
  • Boivin MJ, Bangirana P, Byarugaba J, Opoka RO, Idro R, Jurek AM, et al. Cognitive impairment after cerebral malaria in children: a prospective study. Pediatrics 2007; 119:e360 - 6; http://dx.doi.org/10.1542/peds.2006-2027; PMID: 17224457
  • Beare NA, Southern C, Kayira K, Taylor TE, Harding SP. Visual outcomes in children in Malawi following retinopathy of severe malaria. Br J Ophthalmol 2004; 88:321 - 4; http://dx.doi.org/10.1136/bjo.2003.025924; PMID: 14977760
  • Haslett P. Retinal haemorrhages in Zambian children with cerebral malaria. J Trop Pediatr 1991; 37:86 - 7; http://dx.doi.org/10.1093/tropej/37.2.86; PMID: 2027172
  • Kayembe D, Maertens K, De Laey JJ. [Ocular complications of cerebral malaria]. Bull Soc Belge Ophtalmol 1980; 190:53 - 60; PMID: 7284663
  • Molyneux ME, Taylor TE, Wirima JJ, Borgstein A. Clinical features and prognostic indicators in paediatric cerebral malaria: a study of 131 comatose Malawian children. Q J Med 1989; 71:441 - 59; PMID: 2690177
  • Hero M, Harding SP, Riva CE, Winstanley PA, Peshu N, Marsh K. Photographic and angiographic characterization of the retina of Kenyan children with severe malaria. Arch Ophthalmol 1997; 115:997 - 1003; http://dx.doi.org/10.1001/archopht.1997.01100160167005; PMID: 9258221
  • Essuman VA, Ntim-Amponsah CT, Astrup BS, Adjei GO, Kurtzhals JA, Ndanu TA, et al. Retinopathy in severe malaria in Ghanaian children--overlap between fundus changes in cerebral and non-cerebral malaria. Malar J 2010; 9:232; http://dx.doi.org/10.1186/1475-2875-9-232; PMID: 20704742
  • Biswas J, Fogla R, Srinivasan P, Narayan S, Haranath K, Badrinath V. Ocular malaria. A clinical and histopathologic study. Ophthalmology 1996; 103:1471 - 5; PMID: 8841308
  • Hidayat AA, Nalbandian RM, Sammons DW, Fleischman JA, Johnson TE. The diagnostic histopathologic features of ocular malaria. Ophthalmology 1993; 100:1183 - 6; PMID: 8341499
  • Mehta SA, Ansari AS, Jiandani P. Ophthalmoscopic findings in adult patients with severe falciparum malaria. Ocul Immunol Inflamm 2008; 16:239 - 41; http://dx.doi.org/10.1080/09273940802409977; PMID: 19065421
  • Kochar DK, Shubhakaran, Kumawat BL, Thanvi I, Joshi A, Vyas SP. Ophthalmoscopic abnormalities in adults with falciparum malaria. QJM 1998; 91:845 - 52; http://dx.doi.org/10.1093/qjmed/91.12.845; PMID: 10024950
  • Abu Sayeed A, Maude RJ, Hasan MU, Mohammed N, Hoque MG, Dondorp AM, et al. Malarial retinopathy in Bangladeshi adults. Am J Trop Med Hyg 2011; 84:141 - 7; http://dx.doi.org/10.4269/ajtmh.2011.10-0205; PMID: 21212217
  • Maude RJ, Beare NA, Abu Sayeed A, Chang CC, Charunwatthana P, Faiz MA, et al. The spectrum of retinopathy in adults with Plasmodium falciparum malaria. Trans R Soc Trop Med Hyg 2009; 103:665 - 71; http://dx.doi.org/10.1016/j.trstmh.2009.03.001; PMID: 19344925
  • Beare NA, Southern C, Chalira C, Taylor TE, Molyneux ME, Harding SP. Prognostic significance and course of retinopathy in children with severe malaria. Arch Ophthalmol 2004; 122:1141 - 7; http://dx.doi.org/10.1001/archopht.122.8.1141; PMID: 15302654
  • Hirneiss C, Klauss V, Wilke M, Kampik A, Taylor T, Lewallen S. [Ocular changes in tropical malaria with cerebral involvement--results from the Blantyre Malaria Project]. Klin Monbl Augenheilkd 2005; 222:704 - 8; PMID: 16175479
  • White VA, Lewallen S, Beare N, Kayira K, Carr RA, Taylor TE. Correlation of retinal haemorrhages with brain haemorrhages in children dying of cerebral malaria in Malawi. Trans R Soc Trop Med Hyg 2001; 95:618 - 21; http://dx.doi.org/10.1016/S0035-9203(01)90097-5; PMID: 11816433
  • Lewallen S, White VA, Whitten RO, Gardiner J, Hoar B, Lindley J, et al. Clinical-histopathological correlation of the abnormal retinal vessels in cerebral malaria. Arch Ophthalmol 2000; 118:924 - 8; PMID: 10900105
  • Beare NA, Harding SP, Taylor TE, Lewallen S, Molyneux ME. Perfusion abnormalities in children with cerebral malaria and malarial retinopathy. J Infect Dis 2009; 199:263 - 71; http://dx.doi.org/10.1086/595735; PMID: 18999956
  • Beare NA, Lewallen S, Taylor TE, Molyneux ME. Redefining cerebral malaria by including malaria retinopathy. Future Microbiol 2011; 6:349 - 55; http://dx.doi.org/10.2217/fmb.11.3; PMID: 21449844
  • Medana IM, Day NP, Hien TT, Mai NT, Bethell D, Phu NH, et al. Axonal injury in cerebral malaria. Am J Pathol 2002; 160:655 - 66; http://dx.doi.org/10.1016/S0002-9440(10)64885-7; PMID: 11839586
  • Medana IM, Turner GD. Human cerebral malaria and the blood-brain barrier. Int J Parasitol 2006; 36:555 - 68; http://dx.doi.org/10.1016/j.ijpara.2006.02.004; PMID: 16616145
  • Patnaik JK, Das BS, Mishra SK, Mohanty S, Satpathy SK, Mohanty D. Vascular clogging, mononuclear cell margination, and enhanced vascular permeability in the pathogenesis of human cerebral malaria. Am J Trop Med Hyg 1994; 51:642 - 7; PMID: 7985757
  • Oo MM, Aikawa M, Than T, Aye TM, Myint PT, Igarashi I, et al. Human cerebral malaria: a pathological study. J Neuropathol Exp Neurol 1987; 46:223 - 31; http://dx.doi.org/10.1097/00005072-198703000-00009; PMID: 3546601
  • Anstrom JA, Brown WR, Moody DM, Thore CR, Challa VR, Block SM. Anatomical analysis of the developing cerebral vasculature in premature neonates: absence of precapillary arteriole-to-venous shunts. Pediatr Res 2002; 52:554 - 60; http://dx.doi.org/10.1203/00006450-200210000-00015; PMID: 12357050
  • Ballabh P, Braun A, Nedergaard M. The blood-brain barrier: an overview: structure, regulation, and clinical implications. Neurobiol Dis 2004; 16:1 - 13; http://dx.doi.org/10.1016/j.nbd.2003.12.016; PMID: 15207256
  • Namutangula B, Ndeezi G, Byarugaba JS, Tumwine JK. Mannitol as adjunct therapy for childhood cerebral malaria in Uganda: a randomized clinical trial. Malar J 2007; 6:138; http://dx.doi.org/10.1186/1475-2875-6-138; PMID: 17958887
  • Warrell DA, Looareesuwan S, Warrell MJ, Kasemsarn P, Intaraprasert R, Bunnag D, et al. Dexamethasone proves deleterious in cerebral malaria. A double-blind trial in 100 comatose patients. N Engl J Med 1982; 306:313 - 9; http://dx.doi.org/10.1056/NEJM198202113060601; PMID: 7033788
  • Hoffman SL, Rustama D, Punjabi NH, Surampaet B, Sanjaya B, Dimpudus AJ, et al. High-dose dexamethasone in quinine-treated patients with cerebral malaria: a double-blind, placebo-controlled trial. J Infect Dis 1988; 158:325 - 31; http://dx.doi.org/10.1093/infdis/158.2.325; PMID: 3042874
  • Mohanty S, Mishra SK, Patnaik R, Dutt AK, Pradhan S, Das B, et al. Brain swelling and mannitol therapy in adult cerebral malaria: a randomized trial. Clin Infect Dis 2011; 53:349 - 55; http://dx.doi.org/10.1093/cid/cir405; PMID: 21810747
  • Newton CR, Kirkham FJ, Winstanley PA, Pasvol G, Peshu N, Warrell DA, et al. Intracranial pressure in African children with cerebral malaria. Lancet 1991; 337:573 - 6; http://dx.doi.org/10.1016/0140-6736(91)91638-B; PMID: 1671941
  • Waller D, Crawley J, Nosten F, Chapman D, Krishna S, Craddock C, et al. Intracranial pressure in childhood cerebral malaria. Trans R Soc Trop Med Hyg 1991; 85:362 - 4; http://dx.doi.org/10.1016/0035-9203(91)90291-6; PMID: 1949139
  • Lewallen S, Taylor TE, Molyneux ME, Wills BA, Courtright P. Ocular fundus findings in Malawian children with cerebral malaria. Ophthalmology 1993; 100:857 - 61; PMID: 8510897
  • Potchen MJ, Kampondeni SD, Seydel KB, Birbeck GL, Hammond CA, Bradley WG, et al. Acute brain MRI findings in 120 Malawian children with cerebral malaria: new insights into an ancient disease. AJNR Am J Neuroradiol 2012; 33:1740 - 6; http://dx.doi.org/10.3174/ajnr.A3035; PMID: 22517285
  • Looareesuwan S, Wilairatana P, Krishna S, Kendall B, Vannaphan S, Viravan C, et al. Magnetic resonance imaging of the brain in patients with cerebral malaria. Clin Infect Dis 1995; 21:300 - 9; http://dx.doi.org/10.1093/clinids/21.2.300; PMID: 8562735
  • Medana IM, Day NP, Sachanonta N, Mai NT, Dondorp AM, Pongponratn E, et al. Coma in fatal adult human malaria is not caused by cerebral oedema. Malar J 2011; 10:267; http://dx.doi.org/10.1186/1475-2875-10-267; PMID: 21923924
  • Okoromah CA, Afolabi BB, Wall EC. Mannitol and other osmotic diuretics as adjuncts for treating cerebral malaria. Cochrane Database Syst Rev 2011; CD004615; PMID: 21491391
  • Hawkes M, Opoka RO, Namasopo S, Miller C, Thorpe KE, Lavery JV, et al. Inhaled nitric oxide for the adjunctive therapy of severe malaria: protocol for a randomized controlled trial. Trials 2011; 12:176; http://dx.doi.org/10.1186/1745-6215-12-176; PMID: 21752262
  • Hawkes M, Opoka RO, Namasopo S, Miller C, Conroy AL, Serghides L, et al. Nitric oxide for the adjunctive treatment of severe malaria: hypothesis and rationale. Med Hypotheses 2011; 77:437 - 44; http://dx.doi.org/10.1016/j.mehy.2011.06.003; PMID: 21745716
  • Mestan KK, Marks JD, Hecox K, Huo D, Schreiber MD. Neurodevelopmental outcomes of premature infants treated with inhaled nitric oxide. N Engl J Med 2005; 353:23 - 32; http://dx.doi.org/10.1056/NEJMoa043514; PMID: 16000353