Flavonol-rich dark cocoa significantly decreases plasma endothelin-1 and improves cognition in urban children

Frontiers in Pharmacology

Volumn 4 AUG, Issue , 2013, Pages

  Calderón Garcidueñas, Lilian ^a,b   Mora Tiscareño, Antonieta ^c   Franco Lira, Maricela ^b   Cross, Janet V ^d   Engle, Randall ^e   Aragón Flores, Mariana ^b   Gómez Garza, Gilberto ^c   Jewells, Valerie ^f   Medina Cortina, Humberto ^c   Solorio, Edelmira ^c   Chao, Chih kai ^a   Zhu, Hongtu ^g   Mukherjee, Partha S ^h   Ferreira Azevedo, Lara ⁱ   Torres Jardón, Ricardo ^j   D'Angiulli, Amedeo ^k  

^a UNIVERSITY OF MONTANA   (United States)

^b Secretaria de la Defensa Nacional   (Mexico)

^c INSTITUTO NACIONAL DE PEDIATRÍA   (Mexico)

^d UNIVERSITY OF VIRGINIA   (United States)

^e GEORGIA INSTITUTE OF TECHNOLOGY   (United States)

^f UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^g IL   (United States)

^h BOISE STATE UNIVERSITY   (United States)

ⁱ MINISTRY OF EDUCATION OF BRAZIL   (Brazil)

^j UNIVERSIDAD NACIONAL AUTÓNOMA DE MÉXICO   (Mexico)

^k CARLETON UNIVERSITY   (Canada)

more..

Author keywords

Air pollution; Alzheimer's and Parkinson's disease risk; Children; Cocoa; Cognition

Indexed keywords

ENDOTHELIN 1; FLAVONOL; GAMMA INTERFERON INDUCIBLE PROTEIN 10; GRANULOCYTE COLONY STIMULATING FACTOR; INTERLEUKIN 12; INTERLEUKIN 1BETA; INTERLEUKIN 7; OZONE; PLATELET DERIVED GROWTH FACTOR AA;

AIR POLLUTION; AIR QUALITY; ARTICLE; BASOPHIL; CACAO; CHILD; COGNITION; DIET SUPPLEMENTATION; EOSINOPHIL COUNT; FEMALE; HIPPOCAMPUS; HUMAN; HUMAN EXPERIMENT; MALE; MEMORY; MEXICO; NEUROPROTECTION; NEUTROPHIL COUNT; NORMAL HUMAN; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PARTICULATE MATTER; PROTEIN BLOOD LEVEL; RETICULOCYTE COUNT; SCHOOL CHILD; SCORING SYSTEM; THROMBOCYTE COUNT; URBAN AREA; WHITE MATTER;

EID: 84883531025     PISSN: None     EISSN: 16639812     Source Type: Journal    
DOI: 10.3389/fphar.2013.00104     Document Type: Article

References (112)

1. Adamkiewicz, G., Zota, A. R., Fabian, M. P., Chahine, T., Julien, R., Spengler, J. D., et al. (2011). Moving environmental justice indoors: understanding structural influences on residential exposure patterns in low-income communities. Am. J. Public Health 101(Suppl. 1), 5238-5245. doi: 10.2105/AJPH.2011.300119
2. Akita, M., Kuwahara, M., Itoh, F., Nakano, M., Osakabe, N., Kurosawa, T., et al. (2008). Effects of cacao liquor polyphenols on cardiovascular and autonomic nervous functions in hypercholesterolaemic rabbits. Basic Clin. Phamacol. Toxcol. 103, 581-587. doi: 10.1111/j.1742-7843.2008.00331.x
3. Alosco, M. L., Brickman, A. M., Spitznagel, M. B., Garcia, S. L., Narkhede, A., Griffith, E. Y., et al. (2013). Cerebral perfusion is associated with white matter hyperintensities in older adults with heart failure. Congest. Heart Fail. 19, E29-E34. doi: 10.1111/chf.12025
4. Artzi, M., Aizenstein, O., Abramovitch, R., and Bashat, D. B. (2013). MRI multiparametric hemodynamic characterization of the normal brain. Neuroscience 240, 269-276. doi: 10.1016/j.neuroscience.2013.03.004
5. Block, M. L., and Calderón-Garcidueñas, L. (2009). Air pollution: mechanisms of neuroinflammation and CNS disease. Trends Neurosci. 32, 506-516. doi: 10.1016/j.tins.2009.05.009
6. Bravo-Alvarez, H., and Torres-Jardón, R. (2002). "Air pollution levels and trends in the México City metropolitan area," in: Urban Air Pollution and Forest: Resources at Risk in the Mexico City Air Basin, Chapter 6, eds M. Fenn, L. de Bauer, and T. Hernández, Ecological Studies 156. (New York, NY: Springer-Verlag), 121-159.
7. Calderón-Garcidueñas, L., Franco-Lira, M., Mora-Tiscareño, A., Medina-Cortina, H., Torres-Jardón, R., and Kavanaugh, M. (2013). Early Alzheimer's and Parkinson's disease pathology in urban children: friend versus foe responses- It is time to face the evidence. Biomed. Res. Int. 2013:161687. doi: 10.1155/2013/161687
8. Calderón-Garcidueñas, L., Kavanaugh, M., Block, M. L., D'Angiulli, A., Delgado-Chávez, R., Torres-Jardón, R., et al. (2012a). Neuroinflammation, hyperphosphorilated tau, diffuse amyloid plaques and down- regulation of the cellular prion protein in air pollution exposed children and adults. J. Alzheimer Dis. 28, 93-107.
9. Calderón-Garcidueñas, L., Mora-Tiscareño, A., Styner, M., Gómez-Garza, G., Zhu, H., Torres-Jardón, R., et al. (2012b). White matter hyperintensities, systemic inflammation, brain growth, and cognitive functions in children exposed to air pollution. J. Alzheimers Dis. 31, 183-191.
10. Calderón-Garcidueñas, L., Macias-Parra, M., Hoffmann, H. J., Valencia-Salazar, G., Henríquez-Roldán, C., Monte, O. C., et al. (2009). Immunotoxicity and environment: immunodysregulation and systemic inflammation in children. Toxicol. Pathol. 37, 161-169. doi: 10.1177/0192623308329340
11. Calderón-Garcidueñas, L., Mora-Tiscareño, A., Fordham, L. A., Valencia-Salazar, G., Chung, C. J., Rodriguez-Alcaraz, A., et al. (2003). Respiratory damage in children exposed to urban pollution. Pediatr. Pulmonol. 36, 148-161. doi: 10.1002/ppul.10338
12. Calderón-Garcidueñas, L., Mora-Tiscareño, A., Ontiveros, E., Gómez-Garza, G., Barragán-Mejía, G., Broadway, J., et al. (2008a). Air pollution, cognitive deficits and brain abnormalities: a pilot study with children and dogs. Brain Cogn. 68, 117-127. doi: 10.1016/j.bandc.2008.04.008
13. Calderón-Garcidueñas, L., Villarreal-Calderon, R., Valencia-Salazar, G., Henríquez-Roldán, C., Gutiérrez-Castrellón, P., Torres-Jardón, R., et al. (2008b). Systemic inflammation, endothelial dysfunction, and activation in clinically healthy children exposed to air pollutants. Inhal. Toxicol. 20, 499-506. doi: 10.1080/08958370701864797
14. Calderón-Garcidueñas, L., Vincent, R., Mora-Tiscareño, A., Franco-Lira, M., Henríquez-Roldán, C., Barragán-Mejía, G., et al. (2007). Elevated plasma endothelin-1 and pulmonary arterial pressure in children exposed to air pollution. Environ. Health Perspect. 115, 1248-1253. doi: 10.1289/ehp.9641
15. Campbell, A., Araujo, J. A., Li, H., Sioutas, C., and Kleinman, M. (2009). Particulate matter induced enhancement of inflammatory markers in the brains of apolipoprotein E knockout mice. J. Nanosci. Nanotechnol. 9, 5099-5104. doi: 10.1166/jnn.2009.GR07
16. Cao, L., Xu, C. B., Zhang, Y., Cao, Y. X., and Edvinsson, L. (2011). Second hand smoke exposure induces Raf/ERK/MAPK-mediated upregulation of cerebrovascular endothelin ETA receptors. BMC Neurosci. 12:109. doi: 10.1186/1471-2202-12-109
17. Cao, L., Zhang, Y., Cao, Y. X., Edvinsson, L., and Xu, C. B. (2012). Secondhand smoke exposure causes bronchial hyperreactivity via transcriptionally upregulated endothelin and 5-hydroxytryptamine 2A receptors. PLoS ONE 7:e44170. doi: 10.1371/journal.pone.0044170
18. Castellani, R. J., and Perry, G. (2012). Pathogenesis and disease-modifying therapy in Alzheimer's disease: the flat line of progress. Arch. Med. Res. 43, 694-698. doi: 10.1016/j.arcmed.2012.09.009
19. Chang, L., Munsaka, S. M., Kraft-Terry, S., and Emst, T. (2013). Magnetic resonance spectroscopy to assess neuroinflammation and neuropathic pain. J. Neuroimmune Pharmacol. 8, 576-593. doi: 10.1007/s11481-013-9460-x
20. Cherniack, E. P. (2011). Polyphenols: planting the seeds of treatment for the metabolic syndrome. Nutrition 27, 617-623. doi: 10.1016/j.nut.2010.10.013
21. Crews, W. D. Jr., Harrison, D. W., and Wright, J. W. (2008). A double-blind, placebo-controlled, randomized trial of the effects of dark chocolate and cocoa on variables associated with neuropsychological functioning and cardiovascular health: clinical findings from a sample of healthy, cognitively intact older adults. Am. J. Clin. Nutr. 87, 872-880.
22. D'Angiulli, A., Lipina, S. J., and Olesinska, A. (2012). Explicit and implicit issues in the developmental cognitive neuroscience of social inequality. Front. Hum. Neurosci. 6, 254-260. doi: 10.3389/fnhum.2012.00254
23. D'Haeseller, M., Beelen, R., Fierens, Y., Cambron, M., Vanbinst, A. M., Verborgh, C., et al. (2013). Cerebral hypoperfusion in multiple sclerosis is reversible and mediated by endothelin-1. Proc. Natl. Acad. Sci.U.S.A. 110, 5654-5658. doi: 10.1073/pnas.1222560110
24. D'Haeseller, M., Cambron, M., Vanopdenbosch, L., and De Keyser, J. (2011). Vascular aspects of multiple sclerosis. Lancet Neurol. 10, 657-666. doi: 10.1016/S1474-4422(11)70105-3
25. Daulatzai, M. A. (2012). Quintessential risk factors: their role in promoting cognitive dysfunction and Alzheimer's disease. Neurochem. Res. 37, 2627-2658. doi: 10.1007/s11064-012-0854-6
26. De la Torre, J. C. (2012). A turning point for Alzheimer's disease? Biofactors 38, 78-83. doi: 10.1002/biof.200
27. Desideri, G., Kwik-Uribe, C., Grassi, D., Necozione, S., Ghiadoni, L., Mastroiacovo, D., et al. (2012). Benefits in cognitive function, blood pressure, and insulin resistance through cocoa flavonol consumption in elderly subjects with mild cognitive impairment: the Cocoa, Cognition, and Aging (CoCoA) study. Hypertension 60, 794-801. doi: 10.1161/HYPERTENSIONAHA.112.193060
28. Engle, R. W. (2002). Working memory capacity as executive attention. Curr. Dir. Psychol. Sci. 11, 19-23. doi: 10.1111/1467-8721.00160
29. Engle, R. W. (2010). Role of working-memory capacity in cognitive control. Curr. Anthropol. 51, S17-S26. doi: 10.1086/650572
30. Engle, R. W., and Kane, M. J. (2004). "Executive attention, working memory capacity, and a two-factor theory of cognitive control," in The Psychology of Learning and Motivation, Vol. 44, ed B. Ross (NewYork, NY: Elsevier), 145-199.
31. Engle, R. W., and Oransky, N. (1999). "The evolution from short-term to working memory: Multi-store to dynamic models of temporary storage," in The Nature of Human Cognition, ed R. Sternberg (Cambridge, MA: MIT Press), 515-555.
32. Evans, J., Levy, J., Hammitt, J., Santos-Burgoa, C., Castillejos, M., Caballero-Ramirez, M., et al. (2002). "Health benefits of air pollution control," in Air Quality in the Mexico Megacity: an Integrated Assessment, eds L. T Molina and M. J Molina Kluwer (Dordrecht: Academic Publishers), 103-136. doi: 10.1007/978-94-010-0454-1_4
33. Fassbender, K., Walter, S., Kühl, S., Landmann, R., Ishii, K., Bertsch, T., et al. (2004). The LPS receptor (CD14) links innate-immunity with Alzheimer's disease. FASEB J. 18, 203-205.
34. Field, D. T., Williams, C. M., and Butler, L. T. (2011). Consumption of cocoa flavonols results in an acute improvement in visual and cognitive functions. Physiol. Behav. 103, 255-260. doi: 10.1016/j.physbeh.2011.02.013
35. Fisher, N. D., Sorond, F. A., and Hollenberg, N. K. (2006). Cocoa flavonols and brain perfusion. J. Cardiovasc. Pharmacol. 47(Suppl. 2), S210-S214. doi: 10.1097/00005344-200606001-00017
36. Francis, S. T., Head, K., Morris, P. G., and Macdonald, I. A. (2006). The effect of flavonol-rich cocoa on the fMRI response to a cognitive task in healthy young people. J. Cardiovasc. Pharmacol. 47(Suppl. 2), S215-S220. doi: 10.1097/00005344-200606001-00018
37. Ghosh, D., and Scheepens, A. (2009). Vascular action of polyphenols. Mol. Nutr. Food Res. 53, 322-331. doi: 10.1002/mnfr.200800182
38. Gonsalves, C., and Kalra, V. K. (2010). Endothelin-1 induced macrophage inflammatory protein-1β expression in monocytic cells involves hypoxia-inducible factor 1a and AP-1 and is negatively regulated by microRNA-195. J. Immunol. 185, 6253-6264. doi: 10.4049/jimmunol.1000660
39. Grassi, D., Desideri, G., Necozione, S., Lippi, C., Casale, R., Properzi, G., et al. (2008). Blood pressure is reduced and insulin sensitivity increased in glucose-intolerant, hypertensive subjects after 15 days of consuming high-polyphenol dark chocolate. J. Nutr. 138, 1671-1676.
40. Gu, Y., Yu, S., and Lambert, J. D. (2013). Dietary cocoa ameliorates obesity-related inflammation in high fat-fed mice. Eur. J. Nutr. doi: 10.1007/s00394-013-0510-1. [Epub ahead of print].
41. Guerrero-Romero, F., Aradillas-García, C., Simental-Mendía, L. E., Torres-Rodríguez, M. L., Mendoza-Ede, L., Rosales-Cervantes, J., et al. (2013). Biochemical characteristics and risk factors for insulin resistance at different levels of obesity. Pediatrics 131, e1211-e1217. doi: 10.1542/peds.2012-1421
42. Heaney, R. P. (2013). Dairy intake, dietary adequacy and lactose intolerance. Adv. Nutr. 4, 151-156. doi: 10.3945/an.112.003368
43. Ho, Y. S., Yang, X., Yeung, S. C., Chiu, K., Lau, C. F., Tsang, A. W., et al. (2012). Cigarette smoking accelerated brain aging and induced pre-Alzheimer-like neuropathology in rats. PLoS ONE 7:e36752. doi: 10.1371/journal.pone.0036752
44. Inoue, T., Ohwaki, K., Tamura, A., Tsutsumi, K., Saito, I., and Saito, N. (2013). Subclinical ischemia verified by somatosensory evoked potential amplitude reduction during carotid endarterectomy: negative effects on cognitive performance. J. Neurosurg. 118, 1023-1029. doi: 10.3171/2013.1.JNS121668
45. Jacobs, M. E., Wing, C. S., and Cain, B. D. (2013). An emerging role for microRNA in the regulation of endothelin-1. Front Physiol. 4:22. doi: 10.3389/fphys.2013.00022
46. Jian, H., Yi-Fang, W., Qi, L., Xiai-Song, H., and Gui-Yun, Z. (2012). Cerebral blood flow and metabolic changes in hippocampal regions of a modified rat model with chronic cerebral hypoperfusion. Acta Neurol. Belg. doi: 10.1007/s13760-012-0154-6. [Epub ahead of print].
47. Kaoukis, A., Deftereos, S., Raisakis, K., Giannopoulos, G., Bouras, G., Panagopoulou, V., et al. (2013). The role of endothelin system in cardiovascular disease and the potential therapeutic perspectives of its inhibition. Curr. Top. Med. Chem. 13, 95-114. doi: 10.2174/1568026611313020003
48. Kohan, D. E., Rossi, N. F., Inscho, E. W., and Pollock, D. M. (2011). Regulation of blood pressure and salt homeostasis by endothelin. Physiol. Rev. 91, 1-77. doi: 10.1152/physrev.00060.2009
49. Kolettis, T. M., Barton, M., Langleben, D., and Matsumura, Y. (2013). Endothelin in coronary artery disease and myocardial infarction. Cardiol. Rev. 21, 249-256. doi: 10.1097/CRD.0b013e318283f65a
50. Krishnan, R. M., Adar, S. D., Szpiro, A. A., Jorgensen, N. W., Van Hee, V. C., Barr, R. G., et al. (2012). Vascular responses to long- and short term exposure of fine particulate matter: MESA Air (Multi-Ethnic study of Atherosclerosis and Air Pollution). J. Am. Coll. Cardiol. 60, 2158-2166. doi: 10.1016/j.jacc.2012.08.973
51. Levesque, S., Surace, M. J., McDonald, J., and Block, M. L. (2011a). Air pollution and the brain: subchronic diesel exhaust exposure causes neuroinflammation and elevates early markers of neurodegenerative disease. J. Neuroinflammation 8, 105 doi: 10.1186/1742-2094-8-105
52. Levesque, S., Taetzsch, T., Lull, M. E., Kodavanti, U., Stadler, K., Wagner, A., et al. (2011b). Diesel exhaust activates and primes microglia: air pollution,neuroinflammation and regulation of dopaminergic neurotoxicity. Environ. Health Perspect. 119, 1149-1155. doi: 10.1289/ehp.1002986
53. Lucchini, R. G., Dorman, D. C., Elder, A., and Veronesi, B. (2012). Neurological impacts from inhalation of pollutants and the nose-brain connection. Neurotoxicology 33, 838-841. doi: 10.1016/j.neuro.2011.12.001
54. Lund, A. K., Lucero, J., Lucas, S., Madden, M. C., McDonald, J. D., Seagrave, J. C., et al. (2009). Vehicular emissions induce vascular MMP-9 expression and activity associated with endothelin-1 mediated pathways. Arterioscler. Thromb. Vasc. Biol. 29, 511-517. doi: 10.1161/ATVBAHA.108.176107
55. Matsumoto, G., Nakagawa, N. K., Vieira, R. P., Mauad, T., da Silva, L. F., de André, C. D., et al. (2010). The time course of vasoconstriction and endothelin receptor A expression in pulmonary arterioles of mice continuously exposed to ambient urban levels of air pollution. Environ. Res. 110, 237-243. doi: 10.1016/j.envres.2010.01.003
56. Mauricio, M. D., Aldasoro, M., Ortega, J., and Vila, J. M. (2013). Endothelial dysfunction in morbid obesity. Curr. Pharm. Des. [Epub ahead of print].
57. Messerli, F. H. (2012). Chocolate consumption, cognitive function and Nobel laureates. New Engl. J. Med. 367, 1562-1564. doi: 10.1056/NEJMon1211064
58. Miranda, M. L., Edwards, S. E., Keating, M. H., and Paul, C. J. (2011). Making the environmental justice grade: the relative burden of air pollution exposure in the United States. Int. J. Environ. Res. Public Health 8, 1755-1771. doi: 10.3390/ijerph8061755
59. Miyata, R., Hiraiwa, K., Cheng, J. C., Bai, N., Vincent, R., Francis, G. A., et al. (2013). Statins attenuate the development of atherosclerosis and endothelial dysfunction induced by exposure to urban particulate matter (PM10). Toxicol. Appl. Pharmacol. doi: 10.1016/j.taap.2013.05.033
60. Molina, L. T., Kolb, C. E., de Foy, B., Lamb, B. K., Brune, W. H., Jimenez, J. L., et al. (2007). Air quality in North America's most populous city-overview of the MCMA-2003 campaign. Atmos. Chem. Phys. 7, 2447-2473. doi: 10.5194/acp-7-2447-2007
61. Molina, L. T., Madrinich, S., Gaffney, J. S., Apel, E., de Foy, B., Fast, J., et al. (2010). An overview of the MILAGRO 2006 Campaign: Mexico City emissions and their transport and transformation. Atmos. Chem. Phys. 10, 8697-8760. doi: 10.5194/acp-10-8697-2010
62. Monagas, M., Khan, N., Andres-Lacueva, C., Casas, R., Urpi-Sarda, M., Llorach, R., et al. (2009). Effect of cocoa powder on the modulation of inflammatory biomarkers in patients at high risk of cardiovascular disease. Am. J. Clin. Nutr. 90, 1144-1150. doi: 10.3945/ajcn.2009.27716
63. Moreno, G., Johnson-Shelton, D., and Boles, S. (2013). Prevalence and prediction of overweight and obesity among elementary school students. J. Sch. Health 83, 157-163. doi: 10.1111/josh.12011
64. Nacci, C., Leo, V., De Benedictis, L., Carratù, M. R., Bartolomeo, N., Altomare, M., et al. (2013). Elevated endothelin-1 (ET-1) levels may contribute to hypoadiponectinemia in childhood obesity. J. Clin. Endocrinol. Metab. 98, E683-E693. doi: 10.1210/jc.2012-4119
65. Nehlig, A. (2013). The neuroprotective effects of cocoa flavanol and its influence on cognitive performance. Br. J. Clin. Pharmacol. 75, 716-727.
66. Nguyen, M. D., Julien, J. P., and Rivest, S. (2002). Innate immunity: the missing link in neuroprotection and neurodegeneration? Nat. Rev. Neurosci. 3, 216-227. doi: 10.1038/nrn752
67. Nunomura, A., Moreira, P. I., Castellani, R. J., Lee, H. G., Zhu, X., Smith, M. A., et al. (2012). Oxidative damage to RNA in aging and neurodegenerative disorders. Neurotox. Res. 22, 231-248. doi: 10.1007/s12640-012-9331-x
68. Panneerselvam, M., Tsutsumi, Y. M., Bonds, J. A., Horikawa, Y. T., Saldana, M., Dalton, N. D., et al. (2010). Dark chocolate receptors: epicatechin-induced cardiac protection is dependent on d-opioid receptor stimulation. Am. J. Physiol. Heart Circ. Physiol. 299, H1604-H1609. doi: 10.1152/ajpheart.00073.2010
69. Pase, M. P., Scholey, A. B., Pipingas, A., Kras, M., Nolidin, K., Gibbs, A., et al. (2013). Cocoa polyphenols enhance positive mood states but not cognitive performance: a randomized, placebo-controlled trial. J. Psychopharmacol. 27, 451-458. doi: 10.1177/0269881112473791
70. Patel, J., and D'Souza, J. (2008). Can we now eat chocolate without feeling guilty? J. Am. Pharm. Assoc. 48, 438-440. doi: 10.1331/JAPhA.2008.07128
71. Pradella, F., Morales, A. S., Santos, M. P. A., DePaula, R. F. O., Degaki, K. Y., Longhini, A. L., et al. (2013). Granulocyte-colony-stimulating factor treatment enhances Foxp3 T lymphocytes and modifies the proinflammatory response in experimental autoimmune neuritis. CNS Neurosci. Ther. 19, 529-532. doi: 10.1111/cns.12112
72. Qin, L., Wu, X., Block, M. L., Liu, Y., Breese, G. R., Hong, J. S., et al. (2007). Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia 55, 453-462. doi: 10.1002/glia.20467
73. Rivest, S. (2009). Regulation of innate immune responses in the brain. Nat. Rev. Immunol. 9, 429-439. doi: 10.1038/nri2565
74. Rodrigues, R., Smith, M. A., Wang, X., Perry, G., Lee, H. G., Zhu, X., et al. (2012). Molecular neuropathogenesis of Alzheimer's disease: an interaction model stressing the central role of oxidative stress. Future Neurol. 7, 287-305. doi: 10.2217/fnl.12.27
75. Rodriguez-Mateos, A., Onura-Concha, M. J., Kwik-Uribe, C., Vidal, A., and Spencer, J. P. (2012). Influence of sugar type on the bioavailability of cocoa flavanols. Br. J. Nutr. 108, 2243-2250. doi: 10.1017/S0007114512000475
76. Roher, A. E., Debbins, J. P., Malek-Ahmadi, M., Chen, K., Pipe, J. G., Maze, S., et al. (2012). Cerebral blood flow in Alzheimer's disease. Vasc. Health Risk Manag. 8, 599-611. doi: 10.2147/VHRM.S34874
77. Romanini, C. V., Ferreira, E. D., Bacarin, C. C., Verussa, M. H., de Oliveira, R. M., and Milani, H. (2013). Neurohistological and behavioral changes following the four-vessel occlusion/internal carotid artery model of chronic cerebral hypoperfusion: comparison between normotensive and spontaneously hypertensive rats. Behav. Brain Res. 252, 214-221. doi: 10.1016/j.bbr.2013.05.043
78. Saito, H., Ogasawara, K., Nishimoto, H., Yoshioka, Y., Murakami, T., Fujiwara, S., et al. (2013). Postoperative changes in cerebral metabolites associated with cognitive improvement and impairment after carotid endarterectomy: a 3T Proton MR Spectroscopy Study. Am. J. Neuroradiol. 34, 976-982. doi: 10.3174/ajnr.A3344
79. Santos, R. X., Correia, S. C., Zhu, X., Lee, H. G., Petersen, R. B., Nunomura, A., et al. (2012a). Nuclear and mitochondrial DNA oxidation in Alzheimer's disease. Free Radic. Res. 46, 565-576. doi: 10.3109/10715762.2011.648188
80. Santos, R. X., Correia, S. C., Zhu, X., Smith, M. A., Moreira, P. I., Castellani, R. J., et al. (2012b). Mitochondrial DNA oxidative damage and repair in aging and Alzheimer's disease. Antioxid. Redox Signal. 18, 2444-2457. doi: 10.1089/ars.2012.5039
81. Scholey, A. B., French, S. J., Morris, P. J., Kennedy, D. O., Milne, A. L., and Haskell, C. F. (2010). Consumption of cocoa flavonols results in acute improvements in mood and cognitive performance during sustained mental effort. J. Psychopharmacol. 24, 1505-1514. doi: 10.1177/0269881109106923
82. Selmi, C., Cocchi, C. A., Lanfredini, M., Keen, C. L., Gershwin, M. E. (2008). Chocolate at heart: the anti-inflammatory impact of cocoa flavanols. Mol. Nutr. Food Res. 52, 1340-1348. doi: 10.1002/mnfr.200700435
83. Sharma, H. S., and Sharma, A. (2012). Neurotoxicity of engineered nanoparticles from metals. CNS Neurol. Disord. Drug Targets 11, 65-80. doi: 10.2174/187152712799960817
84. Shiino, M. G., Bauer, S. R., McDonald, A. C., Chowdhury, N. H., Coltart, C. E., and Ding, E. L. (2012). The profile of hippocampal metabolites differs between Alzheimer's disease and subcortical ischemic vascular dementia, as measured by proton magnetic resonance spectroscopy. J. Cereb. Blood Flow Metab. 32, 805-815. doi: 10.1038/jcbfm.2012.9
85. Shipstead, Z., Redick, T. S., Hicks, K. L., and Engle, R. W. (2012). The scope and control of attention as separate aspects of working memory. Memory 20, 608-628. doi: 10.1080/09658211.2012.691519
86. Shrime, M. G., Bauer, S. R., McDonald, A. C., Chowdhury, N. H., Coltart, C. E., and Ding, E. L. (2011). Flavonoid-rich cocoa consumption affects multiple cardiovascular risk factors in a meta-analysis of short-term studies. J. Nutr. 141, 1982-1988. doi: 10.3945/jn.111.145482
87. Simard, A. R., and Rivest, S. (2004). Role of inflammation in the neurobiology of stem cells. Neuro-report 15, 2305-2310. doi: 10.1097/00001756-200410250-00001
88. Sochocka, M., Koutsouraki, E. S., Gasiorowski, K., and Leszek, J. (2013). Vascular oxidative stress and mitochondrial failure in the pathobiology of Alzheimer's disease: new approach to therapy. CNS Neurol. Disord. Drug Targets. [Epub ahead of print].
89. Spadafranca, A., Martinez-Conesa, C., Sirini, S., and Testolin, G. (2010). Effect of dark chocolate on plasma epicatechin levels, DNA resistance to oxidative stress and total antioxidant activity in healthy subjects. Br. J. Nutr. 103, 1008-1014. doi: 10.1017/S0007114509992698
90. Stern, Y. (2012). Cognitive reserve in ageing and Alzheimer's disease. Lancet Neurol. 11, 1006-1012. doi: 10.1016/S1474-4422(12)70191-6
91. Tamagawa, E., Bai, N., Morimoto, K., Gray, C., Mui, T., Yatera, K.,. et al. (2008). Particulate matter exposure induces persistent lung inflammation and endothelial dysfunction. Am. J. Physiol. Lung Cell Mol. Physiol. 295, L79-L85. doi: 10.1152/ajplung.00048.2007
92. Tan, W. C., Qiu, D., Liam, B. L., Ng, T. P., Lee, S. H., van Eeden, S. F., et al. (2000). The human bone marrow response to acute air pollution caused by forest fires. Am. J. Respir. Crit. Care Med. 161, 1213-1217. doi: 10.1164/ajrccm.161.4.9904084
93. Tarantini, L., Bonzini, M., Tripodi, A., Angelici, L., Nordio, F., Cantone, L., et al. (2013). Blood hypomethylation of inflammatory genes mediates the effects of metal-rich airborne pollutants on blood coagulation. Occup. Environ. 70, 418-425. doi: 10.1136/oemed-2012-101079
94. Taylor, W. D., Aizenstein, H. J., and Alexopoulos, G. S. (2013). The vascular depression hypothesis: mechanisms linking vascular disease with depression. Mol. Psychiatry doi: 10.1038/mp.2013.20. [Epub ahead of print].
95. Thomson, E., Kumarathasan, P., Goegan, P., Aubin, R. A., and Vincent, R. (2005). Differential regulation of the lung endothelin system by urban particulate matter and ozone. Toxicol. Sci. 88, 103-113. doi: 10.1093/toxsci/kfi272
96. Thomson, E. M., Kumarathasan, P., Calderón-Garcidueñas, L., and Vincent, R. (2007). Air Pollution alters brain and pituitary endothelin-1 and inducible nitric oxide synthase gene expression. Environ. Res. 105, 224-233. doi: 10.1016/j.envres.2007.06.005
97. Tirsi, A., Duong, M., Tsui, W., Lee, C., and Convit, A. (2013). Retinal vessel abnormalities as a possible biomarker of brain volume loss in obses adolescents. Obesity doi: 10.1002/oby.20450
98. Trickler, W. J., Lantz, S. M., Schrand, A. M., Robinson, B. L., Newport, G. D., Schlager, J. J., et al. (2012). Effects of copper nanoparticles on rat cerebral microvessel endothelial cells. Nanomedicine 7, 835-846. doi: 10.2217/nnm.11.154
99. Vauzour, D. (2012). Dietary polyphenols as modulators of brain functions: biological actions and molecular mechanisms underpinning their beneficial effects. Oxid. Med. Cell Longev. 2012:914273. doi: 10.1155/2012/914273
100. Veras, M. M., Guimarães-Silva, R. M., Caldini, E. G., Saldiva, P. H., Dolhnikoff, M., and Mayhew, T. M. (2012). The effects of particulate ambient air Pollution on the murine umbilical cord and its vessels: a quantitative morphological and immunohistochemical Study. Reprod. Toxicol. 34, 598-606. doi: 10.1016/j.reprotox.2012.08.003
101. Villarreal-Calderón, A., Acuña, H., Villarreal-Calderón, J., Garduño, M., Henríquez-Roldán, C. F., Calderón-Garcidueñas, L., et al. (2002). Assessment of physical education time and after-school outdoor time in elementary and middle school students in south Mexico City: the dilemma between physical fitness and the adverse health effects of outdoor pollutant exposure. Arch. Environ. Health 57, 450-460. doi: 10.1080/00039890209601437
102. Villarreal-Calderon, R., Reed, W., Palacios-Moreno, J., Keefe, S., Herrit, L., Brooks, D., et al. (2012). Urban air Pollution produces up-regulation of myocardial inflammatory genes and dark chocolate provides cardioprotection. Exp. Toxicol. Pathol. 64, 297-306. doi: 10.1016/j.etp.2010.09.002
103. Villarreal-Calderon, R., Torres-Jardon, R., Pérez-Guillé, B., Maronpot, R. R., Reed, W., Zhu, H., and Calderón-Garcidueñas, L. (2010). Urban air pollution targets the dorsal vagal complex and dark chocolate offers neuroprotection. Int. J. Toxicol. 29, 604-615. doi: 10.1177/1091581810383587
104. Villeneuve, P. J., Johnson, J. Y., Pasichnvk, D., Lowes, J., Kirkland, S., and Rowe, B. H. (2012). Short-term effects of ambient air pollution on stroke: who is most vulnerable? Sci. Total Environ. 430, 193-201. doi: 10.1016/j.scitotenv.2012.05.002
105. Watanabe, T., Shiino, A., and Akiguchi, L. (2012). Hippocampal metabolites and memory performances in patients with amnestic mild cognitive impairment and Alzheimer's disease. Neurobiol. Learn. Mem. 97, 289-293. doi: 10.1016/j.nlm.2012.01.006
106. Williams, R. J., and Spencer, J. P. (2012). Flavonoids, cognition and dementia: actions, mechanisms and potential therapeutic utility for Alzheimer disease. Free Radic. Biol. Med. 52, 35-45. doi: 10.1016/j.freeradbiomed.2011.09.010
107. Win-Shwe, T. T., and Fujimaki, H. (2011). Nanoparticles and neurotoxicity. Int. J. Mol. Sci. 12, 6267-6280. doi: 10.3390/ijms12096267
108. Wu, J., Wang, C., Sun, J., and Xue, Y. (2011). Neurotoxicity of silica nanoparticles: brain localization and dopaminergic neurons damage pathways. ACS Nano 5, 4476-4489. doi: 10.1021/nn103530b
109. Yan, B., Wei, J. J., Yuan, Y., Sun, R., Li, D., Luo, J., et al. (2013a). IL-6 cooperates with G-CSF to induce protumor function of neutrophils in bone marrow by enhancing STAT3 activation. J. Immunol. 190, 5882-5893. doi: 10.4049/jimmunol.1201881
110. Yan, M. H., Wang, X., and Zhu, X. (2013b). Mitochondrial defects and oxidative stress in Alzheimer disease and Parkinson disease. Free Radic. Biol. Med. 62, 90-101. doi: 10.1016/j.freeradbiomed.2012.11.014
111. Young, G. S., Fox, M. A., Trush, M., Kanarek, N., Glass, T. A., and Curriero, F. C. (2012). Differential exposure to hazardous air pollution in the United States: a multilevel analysis of urbanization and neighborhood socioeconomic deprivation. Int. J. Environ. Res. Public Health 9, 2204-2225. doi: 10.3390/ijerph9062204
112. Yuen, T. J., Johnson, K. R., Miron, V. E., Zhao, C., Quandt, J., Harrisingh, M. C., et al. (2013). Identification of endothelin 2 as an inflammatory factor that promotes central nervous system remyelination. Brain 136(Pt 4), 1035-1047. doi: 10.1093/brain/awt024