PPARγ Agonists Improve Survival and Neurocognitive Outcomes in Experimental Cerebral Malaria and Induce Neuroprotective Pathways in Human Malaria

PLoS Pathogens

Volumn 10, Issue 3, 2014, Pages

  Serghides, Lena ^a,b,c   McDonald, Chloe R ^b,d   Lu, Ziyue ^b,d   Friedel, Miriam ^e   Cui, Cheryl ^d   Ho, Keith T ^d   Mount, Howard T J ^d   Sled, John G ^d,e   Kain, Kevin C ^a,b,d  

^a UNIVERSITY HEALTH NETWORK   (Canada)

^b UNIVERSITY HEALTH NETWORK   (Canada)

^c WOMEN S COLLEGE HOSPITAL   (Canada)

^d UNIVERSITY OF TORONTO   (Canada)

^e HOSPITAL FOR SICK CHILDREN   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ANGIOPOIETIN 1; ANGIOPOIETIN 2; ARTESUNATE; BRAIN DERIVED NEUROTROPHIC FACTOR; CATALASE; COPPER ZINC SUPEROXIDE DISMUTASE; INTERLEUKIN 6; MEFLOQUINE; MONOCYTE CHEMOTACTIC PROTEIN 1; NERVE GROWTH FACTOR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA AGONIST; PIOGLITAZONE; PLACEBO; ROSIGLITAZONE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BEHAVIOR; BLOOD BRAIN BARRIER; BLOOD VESSEL PERMEABILITY; BRAIN ATROPHY; BRAIN MALARIA; COGNITION; COGNITIVE DEFECT; CONTROLLED STUDY; DISEASE SEVERITY; ENZYME LINKED IMMUNOSORBENT ASSAY; FEMALE; HISTOLOGY; HUMAN; MOUSE; NEUROPROTECTION; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; OUTCOME ASSESSMENT; OXIDATIVE STRESS; PARASITEMIA; RANDOMIZED CONTROLLED TRIAL (TOPIC); REAL TIME POLYMERASE CHAIN REACTION; SURVIVAL RATE; TISSUE INJURY;

ANIMALS; ANTIMALARIALS; BRAIN; BRAIN-DERIVED NEUROTROPHIC FACTOR; DISEASE MODELS, ANIMAL; ENZYME-LINKED IMMUNOSORBENT ASSAY; FEMALE; HUMANS; MALARIA, CEREBRAL; MICE; MICE, INBRED BALB C; MICE, INBRED C57BL; MICE, KNOCKOUT; NEUROPROTECTIVE AGENTS; PPAR GAMMA; RANDOMIZED CONTROLLED TRIALS AS TOPIC; REAL-TIME POLYMERASE CHAIN REACTION; RIBONUCLEASE, PANCREATIC; THIAZOLIDINEDIONES;

EID: 84897463097     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1003980     Document Type: Article

References (64)

1. Dondorp A, Nosten F, Stepniewska K, Day N, White N, et al. (2005) Artesunate versus quinine for treatment of severe falciparum malaria, a randomised trial. Lancet 366: 717-725.
2. Dondorp AM, Fanello CI, Hendriksen IC, Gomes E, Seni A, et al. (2010) Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT), an open-label, randomised trial. Lancet 376: 1647-1657.
3. John CC, Kutamba E, Mugarura K, Opoka RO, (2010) Adjunctive therapy for cerebral malaria and other severe forms of Plasmodium falciparum malaria. Expert Rev Anti Infect Ther 8: 997-1008.
4. John CC, Bangirana P, Byarugaba J, Opoka RO, Idro R, et al. (2008) Cerebral malaria in children is associated with long-term cognitive impairment. Pediatrics 122: e92-99.
5. Boivin MJ, Bangirana P, Byarugaba J, Opoka RO, Idro R, et al. (2007) Cognitive impairment after cerebral malaria in children, a prospective study. Pediatrics 119: e360-366.
6. Birbeck G, Molyneux ME, Kaplan PW, Seydel KB, Chimalizeni YF, et al. (2010) Blantyre Malaria Project Epilepsy Study (BMPES) of neurological outcomes in retinopathy-positive paediatric cerebral malaria survivors: a prospective cohort study. Lancet Neurol 9: 1173-1181.
7. Fernando SD, Rodrigo C, Rajapakse S, (2010) The hidden burden of malaria, cognitive impairment following infection. Malaria J 9: 366.
8. Taylor TE, Fu WJ, Carr RA, Whitten RO, Mueller JS, et al. (2004) Differentiating the pathologies of cerebral malaria by postmortem parasite counts. Nat Med 10: 143-145.
9. White VA, Lewallen S, Beare N, Kayira K, Carr RA, et al. (2001) Correlation of retinal haemorrhages with brain haemorrhages in children dying of cerebral malaria in Malawi. Trans R Soc Trop Med Hyg 95: 618-621.
10. Medana IM, Day NP, Hien TT, Mai NT, Bethell D, et al. (2002) Axonal injury in cerebral malaria. Am J Pathol 160: 655-666.
11. Nacer A, Movilla A, Baer K, Mikolajczak SA, Kappe SH, et al. (2012) Neuroimmunological blood brain opening in experimental cerebral malaria. PloS Pathog 8: e1002982.
12. Berger J, Moller DE, (2002) The mechanism of action of PPARs. Ann Rev Med 53: 409-435.
13. Lehrke M, Lazar MA, (2005) The many faces of PPARgamma. Cell 123: 993-999.
14. Kapadia R, Yi JH, Vemuganti R, (2008) Mechanisms of anti-inflammatory and neuroprotective actions of PPAR-gamma agonists. Front Biosci 13: 1813-1826.
15. Jin J, Albertz J, Guo Z, Peng Q, Rudow G, et al. (2013) Neuroprotective effects of PPAR-γ agonist rosiglitazone in N171-82Q mouse model of Huntington's disease. J Neurochem 125: 410-419.
16. Serghides L, Patel SN, Ayi K, Lu Z, Gowda DC, et al. (2009) Rosiglitazone modulates the innate immune response to Plasmodium falciparum infection and improves outcome in experimental cerebral malaria. J Infect Dis 199: 1536-1545.
17. Boggild AK, Krudsood S, Patel SN, Serghides L, Tangpukdee N, et al. (2009) Use of peroxisome proliferator-activated receptor gamma agonists as adjunctive treatment for Plasmodium falciparum malaria, a randomized, double-blind, placebo-controlled trial. Clin Infect Dis 49: 841-849.
18. Kim H, Higgins S, Liles WC, Kain KC, (2011) Endothelial activation and dysregulation in malaria, a potential target for novel therapeutics. Curr Opion Hematol 18: 177-185.
19. Franke-Fayard B, Waters AP, Janse CJ, (2006) Real-time in vivo imaging of transgenic bioluminescent blood stages of rodent malaria parasites in mice. Nat Protoc 1: 476-485.
20. Jeansson M, Gawlik A, Anderson G, Li C, Kerjaschki D, et al. (2011) Angiopoietin-1 is essential in mouse vasculature during development and in response to injury. J Clin Invest 121: 2278-2289.
21. Carroll RW, Wainwright MS, Kim KY, Kidambi T, Gomez ND, et al. (2010) A rapid murine coma and behavior scale for quantitative assessment of murine cerebral malaria. PLoS One 5: e13124.
22. Reis PA, Comim CM, Hermani F, Silva B, Barichello T, et al. (2010) Cognitive dysfunction is sustained after rescue therapy in experimental cerebral malaria, and is reduced by additive antioxidant therapy. PLoS Pathog 24: e1000963.
23. Pabon A, Carmona J, Burgos LC, Blair S, (2003) Oxidative stress in patients with non-complicated malaria. Clin Biochem 36: 71-78.
24. Skaper SD, (2012) The neurotrophin family of neurotrophic factors: an overview. Methods Mol Biol 846: 1-12.
25. Linares M, Marin-Garcia P, Perez-Benavente S, Sanchez-Nogueiro J, Puyet A, et al. (2013) Brain-derived neurotrophic factor and the course of experimental cerebral malaria. Brain Res 1490: 210-224.
26. Huang EJ, Reichardt LF (2003) Trk receptors, roles in neuronal signal transduction. Annu Rev Biochem 72, 609-642.
27. Dai M, Reznik SE, Spray DC, Weiss LM, Tanowitz HB, et al. (2010) Persistent cognitive and motor deficits after successful antimalarial treatment in murine cerebral malaria. Microbes Infect 12: 1198-1207.
28. Lerch JP, Yiu AP, Martinez-Canabal A, Pekar T, Bohbot VD, et al. (2011) Maze training in mice induces MRI-detectable brain shape changes specific to the type of learning. Neuroimage 54: 2086-2095.
29. Potchen MJ, Birbeck GL, Demarco JK, Kampondeni SD, Beare N, et al. (2010) Neuroimaging findings in children with retinopathy-confirmed cerebral malaria. Eur J Radiol 74: 262-268.
30. Kampondeni SD, Potchen MJ, Beare NA, Seydel KB, Glover SJ, et al. (2013) MRI findings in a cohort of brain injured survivors of pediatric cerebral malaria. Am J Trop Med Hyg 88: 542-546.
31. Lerch JP, Sled JG, Henkelman RM, (2011) MRI phenotyping of genetically altered mice. Methods Mol Biol 711: 349-361.
32. Dorr AE, Lerch JP, Spring S, Kabani N, Henkelman RM, (2008) High resolution three-dimensional brain atlas using an average magnetic resonance image of 40 adult C57Bl/6J mice. Neuroimage 42: 60-69.
33. Boivin MJ, Gladstone MJ, Vokhiwa M, Birbeck GL, Magen JG, et al. (2011) Developmental outcomes in Malawian children with retinopathy-positive cerebral malaria. Trop Med Int Health 16: 263-271.
34. Kihara M, Carter JA, Holding PA, Vargha-Khadem F, Scott RC, et al. (2009) Impaired everyday memory associated with encephalopathy of severe malaria, the role of seizures and hippocampal damage. Malaria J 8: 273.
35. Carter JA, Mung'ala-Odera V, Neville BG, Murira B, Mturi N, et al. (2005) Persistent neurocognitive impairments associated with severe falciparum malaria in Kenyan children. J Neurol Neurosurg Psychiatry 76: 476-481.
36. Masi G, Brovedani P, (2011) The hippocampus, neurotrophic factors and depression, possible implications for the pharmacotherapy of depression. CNS Drugs 25: 913-931.
37. Van der Werf YD, Witter MP, Uylings HB, Jolles J (2000) Neuropsychology of infarctions in the thalamus, a review. Neuropsychologia 38, 613-627.
38. Pozzilli C, Bastianello S, Padovani A, Passafiume D, Millefiorini E, et al. (1991) Anterior corpus callosum atrophy and verbal fluency in multiple sclerosis. Cortex 27: 441-445.
39. Hines M, Chiu L, McAdams LA, Bentler PM, Lipcamon J, (1992) Cognition and the corpus callosum, verbal fluency, visuospatial ability, and language lateralization related to midsagittal surface areas of callosal subregions. Behav Neurosci 106: 3-14.
40. Aggleton JP, O'Mara SM, Vann SD, Wright NF, Tsanov M, et al. (2010) Hippocampal-anterior thalamic pathways for memory, uncovering a network of direct and indirect actions. Eur J Neurosci 31: 2292-2307.
41. Potchen MJ, Kampondeni SD, Seydel KB, Birbeck GL, Hammond CA, 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.
42. Comim CM, Reis PA, Frutuso VS, Fries GR, Fraga DB, et al. (2012) Effects of experimental cerebral malaria in memory, brain-derived neurotrophic factor and acetylcholinesterase activity in the hippocampus of survivor mice. Neurosci Lett 523: 104-107.
43. Gomez-Palacio-Schjetnan A, Escobar ML, (2013) Neurotrophins and synaptic plasticity. Curr Top Behav Neurosci 15: 117-136.
44. Shi Q, Zhang P, Zhang J, Chen X, Lu H, et al. (2009) Adenovirus-mediated brain-derived neurotrophic factor expression regulated by hypoxia response element protects brain from injury of transient middle cerebral artery occlusion in mice. Neurosci Lett 465: 220-225.
45. Barichello T, Belarmino E Jr, Comim CM, Cipriano AL, Generoso JS, et al. (2010) Correlation between behavioral deficits and decreased brain-derived neurotrophic factor in neonatal meningitis. J Neuroimmunol 223: 73-76.
46. Bekinschtein P, Cammarota M, Katche C, Slipczuk L, Rossato JI, et al. (2008) BDNF is essential to promote persistence of long-term memory storage. Proc. Natl Acad Sci USA 105: 2711-2716.
47. Canals JM, Pineda JR, Torres-Peraza JF, Bosch M, Martin-Ibanez R, et al. (2004) Brain-derived neurotrophic factor regulates the onset and severity of motor dysfunction associated with enkephalinergic neuronal degeneration in Huntington's disease. J Neurosci 24: 7727-7739.
48. Klein AB, Williamson R, Santini MA, Clemmensen C, Ettrup A, et al. (2011) Blood BDNF concentrations reflect brain-tissue BDNF levels across species. Int J Neuropsychopharmacol 14: 347-353.
49. Sofroniew MV, Howe CL, Mobley WC, (2001) Nerve growth factor signaling, neuroprotection, and neural repair. Annu Rev Neurosci 24: 1217-1281.
50. Lovegrove FE, Tangpukdee N, Opoka RO, Lafferty EI, Rajwans N, 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.
51. Conroy AL, Glover SJ, Hawkes M, Erdman LK, Seydel KB, 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.
52. Yeo TW, Lampah DA, Gitawati R, Tjitra E, Kenangalem E, et al. (2008) Angiopoietin-2 is associated with decreased endothelial nitric oxide and poor clinical outcome in severe falciparum malaria. Proc Natl Acad Sci U S A 105: 17097-17102.
53. Narsaria N, Mohanty C, Das BK, Mishra SP, Prasad R, (2012) Oxidative stress in children with severe malaria. J Trop Pediatr 58: 147-150.
54. Drew PD, Xu J, Racke MK, (2008) PPAR-gamma, therapeutic potential for multiple sclerosis. PPAR Res 2008: 627463.
55. Vemuganti R, (2008) Therapeutic potential of PPARγ activation in stroke. PPAR Res 2008: 461981.
56. Bright JJ, Kanakasabai S, Chearwae W, Chakraborty S, (2008) PPAR regulation of inflammation signaling in CNS diseases. PPAR Res 2008: 658520.
57. Mandrekar-Colucci S, Karlo JC, Landreth GE, (2012) Mechanisms underlying the rapid peroxisome proliferator-activated receptor-γ-mediated amyloid clearance and reversal of cognitive deficits in a murine model of Alzheimer's disease. J Neurosci 32: 10117-10128.
58. Escribano L, Simón AM, Pérez-Mediavilla A, Salazar-Colocho P, Río JD, et al. (2009) Rosiglitazone reverses memory decline and hippocampal glucocorticoid receptor down-regulation in an Alzheimer's disease mouse model. Biochem Biophys Res Commun 379: 406-410.
59. Schintu N, Frau L, Ibba M, Caboni P, Garau A, et al. (2009) PPAR-gamma-mediated neuroprotection in a chronic mouse model of Parkinson's disease. Eur J Neurosci 29: 954-963.
60. Watson GS, Cholerton BA, Reger MA, Baker LD, Plymate SR, et al. (2005) Preserved cognition in patients with early Alzheimer disease and amnestic mild cognitive impairment during treatment with rosiglitazone, a preliminary study. Am J Geriatr Psychiatry 13: 950-958.
61. Kaiser CC, Shukla DK, Stebbins GT, Skias DD, Jeffery DR, et al. (2009) A pilot test of pioglitazone as an add-on in patients with relapsing remitting multiple sclerosis. J Neuroimmunol 211: 124-130.
62. Serghides L, Kim H, Lu Z, Kain DC, Miller C, 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.
63. Francis BM, Kim J, Barakat ME, Fraenki S, Yucel YH, et al. (2012) Object recognition memory and BDNF expression are reduced in young TgCRND8 mice. Neurobiol Aging 33: 555-563.
64. Cahill LS, Laliberte CL, Ellegood J, Spring S, Gleave JA, et al. (2012) Preparation of fixed mouse brains for MRI. Neuroimage 60: 933-939.