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Neuropathology of cigarette smoking

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Abstract

It is well established that cigarette smoking is hazardous to health and is a risk factor for many chronic diseases. However, its impact on the brain, whether it be from prenatal exposure to maternal cigarette smoking, cerebrovascular disease, Alzheimer’s disease (AD) or Parkinson’s disease, is still not very clear. Neuroimaging and neuropathological investigations suggest that there are heterogeneous effects of cigarette smoking on the brain. On the one hand, it is quite clear that cigarette smoking causes damage to endothelial cells, resulting in increased risk of cerebrovascular disease. On the other hand, it seems to be associated with different Alzheimer’s pathologies in post-mortem brains and experimental models, despite the fact that epidemiological studies clearly indicate a positive correlation between cigarette smoking and increased risk for AD. Interestingly, cigarette smoking appears to be associated with reduced Parkinson’s pathology in post-mortem brains. However, although nicotine in cigarettes may have some neuroprotective actions, the effects of all the other toxic compounds in cigarettes cannot be ignored. It is, therefore, our aim to summarize what is known about the neuropathology of cigarette smoking and, in particular, its implications for neurodegenerative diseases.

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References

  1. Abbruscato TJ, Lopez SP, Mark KS, Hawkins BT, Davis TP (2002) Nicotine and cotinine modulate cerebral microvascular permeability and protein expression of ZO-1 through nicotinic acetylcholine receptors expressed on brain endothelial cells. J Pharm Sci 91:2525–2538

    CAS  PubMed  Google Scholar 

  2. Abdel-Rahman A, Dechkovskaia A, Mehta-Simmons H, Guan X, Khan W, bou-Donia M (2003) Increased expression of glial fibrillary acidic protein in cerebellum and hippocampus: differential effects on neonatal brain regional acetylcholinesterase following maternal exposure to combined chlorpyrifos and nicotine. J Toxicol Environ Health A 66:2047–2066

    CAS  PubMed  Google Scholar 

  3. Abdel-Rahman A, Dechkovskaia AM, Mehta-Simmons H et al (2004) Maternal exposure to nicotine and chlorpyrifos, alone and in combination, leads to persistently elevated expression of glial fibrillary acidic protein in the cerebellum of the offspring in late puberty. Arch Toxicol 78:467–476

    CAS  PubMed  Google Scholar 

  4. Ahlsen G, Rosengren L, Belfrage M et al (1993) Glial fibrillary acidic protein in the cerebrospinal fluid of children with autism and other neuropsychiatric disorders. Biol Psychiatry 33:734–743

    CAS  PubMed  Google Scholar 

  5. Alberg A (2002) The influence of cigarette smoking on circulating concentrations of antioxidant micronutrients. Toxicology 180:121–137

    CAS  PubMed  Google Scholar 

  6. Ali M, Yu Z, Jabbour PM et al (2012) Cigarette smoke directly produces a pro-inflammatory/matrix remodeling phenotype in cerebral vascular smooth muscle cells via KLF4: a potential mechanism for cerebral aneurysm pathogenesis. Stroke 43:A112

    Google Scholar 

  7. Almeida OP, Garrido GJ, Lautenschlager NT, Hulse GK, Jamrozik K, Flicker L (2008) Smoking is associated with reduced cortical regional gray matter density in brain regions associated with incipient Alzheimer disease. Am J Geriatr Psychiatry 16:92–98

    PubMed  Google Scholar 

  8. Anblagan D, Jones NW, Costigan C et al (2013) Maternal smoking during pregnancy and fetal organ growth: a magnetic resonance imaging study. PLoS ONE 8:e67223

    CAS  PubMed Central  PubMed  Google Scholar 

  9. Aoki T, Kataoka H, Ishibashi R, Nozaki K, Morishita R, Hashimoto N (2009) Reduced collagen biosynthesis is the hallmark of cerebral aneurysm: contribution of interleukin-1beta and nuclear factor-kappaB. Arterioscler Thromb Vasc Biol 29:1080–1086

    CAS  PubMed  Google Scholar 

  10. Aoki T, Kataoka H, Shimamura M et al (2007) NF-kappaB is a key mediator of cerebral aneurysm formation. Circulation 116:2830–2840

    CAS  PubMed  Google Scholar 

  11. Back SA, Kroenke CD, Sherman LS et al (2011) White matter lesions defined by diffusion tensor imaging in older adults. Ann Neurol 70:465–476

    PubMed Central  PubMed  Google Scholar 

  12. Bailey EL, Smith C, Sudlow CL, Wardlaw JM (2012) Pathology of lacunar ischemic stroke in humans—a systematic review. Brain Pathol 22:583–591

    PubMed  Google Scholar 

  13. Bakhru A, Erlinger TP (2005) Smoking cessation and cardiovascular disease risk factors: results from the Third National Health and Nutrition Examination Survey. PLoS Med 2:e160

    PubMed Central  PubMed  Google Scholar 

  14. Baloyannis SJ (2011) Mitochondria are related to synaptic pathology in Alzheimer’s disease. Int J Alzheimers Dis 2011:305395

    PubMed Central  PubMed  Google Scholar 

  15. Barbieri SS, Zacchi E, Amadio P et al (2011) Cytokines present in smokers’ serum interact with smoke components to enhance endothelial dysfunction. Cardiovasc Res 90:475–483

    CAS  PubMed  Google Scholar 

  16. Barnes DE, Yaffe K (2011) The projected effect of risk factor reduction on Alzheimer’s disease prevalence. Lancet Neurol 10:819–828

    PubMed Central  PubMed  Google Scholar 

  17. Batty GD, Der G, Deary IJ (2006) Effect of maternal smoking during pregnancy on offspring’s cognitive ability: empirical evidence for complete confounding in the US national longitudinal survey of youth. Pediatrics 118:943–950

    PubMed  Google Scholar 

  18. Bennett DS, Mohamed FB, Carmody DP et al (2009) Response inhibition among early adolescents prenatally exposed to tobacco: an fMRI study. Neurotoxicol Teratol 31:283–290

    CAS  PubMed Central  PubMed  Google Scholar 

  19. Bernhard D, Moser C, Backovic A, Wick G (2007) Cigarette smoke—an aging accelerator? Exp Gerontol 42:160–165

    CAS  PubMed  Google Scholar 

  20. Boets B, Ghesquiere P, van Wieringen A, Wouters J (2007) Speech perception in preschoolers at family risk for dyslexia: relations with low-level auditory processing and phonological ability. Brain Lang 101:19–30

    PubMed  Google Scholar 

  21. Borsello T, Forloni G (2007) JNK signalling: a possible target to prevent neurodegeneration. Curr Pharm Des 13:1875–1886

    CAS  PubMed  Google Scholar 

  22. Bradford ST, Stamatovic SM, Dondeti RS, Keep RF, Andjelkovic AV (2011) Nicotine aggravates the brain postischemic inflammatory response. Am J Physiol Heart Circ Physiol 300:H1518–H1529

    CAS  PubMed  Google Scholar 

  23. Brody AL, Mandelkern MA, Jarvik ME et al (2004) Differences between smokers and nonsmokers in regional gray matter volumes and densities. Biol Psychiatry 55:77–84

    PubMed  Google Scholar 

  24. Broe GA, Henderson AS, Creasey H et al (1990) A case-control study of Alzheimer’s disease in Australia. Neurology 40:1698–1707

    CAS  PubMed  Google Scholar 

  25. Butler NR, Goldstein H (1973) Smoking in pregnancy and subsequent child development. Br Med J 4:573–575

    CAS  PubMed Central  PubMed  Google Scholar 

  26. Church DF, Pryor WA (1985) Free-radical chemistry of cigarette smoke and its toxicological implications. Environ Health Perspect 64:111–126

    CAS  PubMed Central  PubMed  Google Scholar 

  27. Cooper JK, Mungas D (1993) Risk factor and behavioral differences between vascular and Alzheimer’s dementias: the pathway to end-stage disease. J Geriatr Psychiatry Neurol 6:29–33

    CAS  PubMed  Google Scholar 

  28. Court JA, Johnson M, Religa D et al (2005) Attenuation of Abeta deposition in the entorhinal cortex of normal elderly individuals associated with tobacco smoking. Neuropathol Appl Neurobiol 31:522–535

    CAS  PubMed  Google Scholar 

  29. Cowperthwaite B, Hains SM, Kisilevsky BS (2007) Fetal behavior in smoking compared to non-smoking pregnant women. Infant Behav Dev 30:422–430

    CAS  PubMed  Google Scholar 

  30. Csiszar A, Podlutsky A, Wolin MS, Losonczy G, Pacher P, Ungvari Z (2009) Oxidative stress and accelerated vascular aging: implications for cigarette smoking. Front Biosci 14:3128–3144

    CAS  Google Scholar 

  31. Csordas A, Bernhard D (2013) The biology behind the atherothrombotic effects of cigarette smoke. Nat Rev Cardiol 10:219–230

    CAS  PubMed  Google Scholar 

  32. Csordas A, Wick G, Laufer G, Bernhard D (2008) An evaluation of the clinical evidence on the role of inflammation and oxidative stress in smoking-mediated cardiovascular disease. Biomark Insights 3:127–139

    CAS  PubMed Central  PubMed  Google Scholar 

  33. Deng J, Shen C, Wang YJ et al (2010) Nicotine exacerbates tau phosphorylation and cognitive impairment induced by amyloid-beta 25-35 in rats. Eur J Pharmacol 637:83–88

    CAS  PubMed  Google Scholar 

  34. Derauf C, Lester BM, Neyzi N et al (2012) Subcortical and cortical structural central nervous system changes and attention processing deficits in preschool-aged children with prenatal methamphetamine and tobacco exposure. Dev Neurosci 34:327–341

    CAS  PubMed  Google Scholar 

  35. Ekblad M, Gissler M, Lehtonen L, Korkeila J (2010) Prenatal smoking exposure and the risk of psychiatric morbidity into young adulthood. Arch Gen Psychiatry 67:841–849

    PubMed  Google Scholar 

  36. Ekblad M, Korkeila J, Parkkola R, Lapinleimu H, Haataja L, Lehtonen L (2010) Maternal smoking during pregnancy and regional brain volumes in preterm infants. J Pediatr 156:185–190

    CAS  PubMed  Google Scholar 

  37. Eliez S, Reiss AL (2000) MRI neuroimaging of childhood psychiatric disorders: a selective review. J Child Psychol Psychiatry 41:679–694

    CAS  PubMed  Google Scholar 

  38. Eppolito AK, Bachus SE, McDonald CG, Meador-Woodruff JH, Smith RF (2010) Late emerging effects of prenatal and early postnatal nicotine exposure on the cholinergic system and anxiety-like behavior. Neurotoxicol Teratol 32:336–345

    CAS  PubMed  Google Scholar 

  39. Eppolito AK, Smith RF (2006) Long-term behavioral and developmental consequences of pre- and perinatal nicotine. Pharmacol Biochem Behav 85:835–841

    CAS  PubMed  Google Scholar 

  40. Ezzati M, Lopez AD (2003) Estimates of global mortality attributable to smoking in 2000. Lancet 362:847–852

    PubMed  Google Scholar 

  41. Feigin VL, Rinkel GJ, Lawes CM, Algra A, Bennett DA, van Gijn J, Anderson CS (2005) Risk factors for subarachnoid hemorrhage: an updated systematic review of epidemiological studies. Stroke 36:2773–2780

    PubMed  Google Scholar 

  42. Filipek PA, Semrud-Clikeman M, Steingard RJ, Renshaw PF, Kennedy DN, Biederman J (1997) Volumetric MRI analysis comparing subjects having attention-deficit hyperactivity disorder with normal controls. Neurology 48:589–601

    CAS  PubMed  Google Scholar 

  43. Fogelman K (1980) Smoking in pregnancy and subsequent development of the child. Child Care Health Dev 6:233–249

    CAS  PubMed  Google Scholar 

  44. French LR, Schuman LM, Mortimer JA, Hutton JT, Boatman RA, Christians B (1985) A case-control study of dementia of the Alzheimer type. Am J Epidemiol 121:414–421

    CAS  PubMed  Google Scholar 

  45. Fried PA, O’Connell CM, Watkinson B (1992) 60- and 72-month follow-up of children prenatally exposed to marijuana, cigarettes, and alcohol: cognitive and language assessment. J Dev Behav Pediatr 13:383–391

    CAS  PubMed  Google Scholar 

  46. Fried PA, Watkinson B (1990) 36- and 48-month neurobehavioral follow-up of children prenatally exposed to marijuana, cigarettes, and alcohol. J Dev Behav Pediatr 11:49–58

    CAS  PubMed  Google Scholar 

  47. Gallinat J, Meisenzahl E, Jacobsen LK et al (2006) Smoking and structural brain deficits: a volumetric MR investigation. Eur J Neurosci 24:1744–1750

    PubMed  Google Scholar 

  48. Gilman SE, Gardener H, Buka SL (2008) Maternal smoking during pregnancy and children’s cognitive and physical development: a causal risk factor? Am J Epidemiol 168:522–531

    PubMed  Google Scholar 

  49. Giwa MO, Williams J, Elderfield K et al (2012) Neuropathologic evidence of endothelial changes in cerebral small vessel disease. Neurology 78:167–174

    CAS  PubMed  Google Scholar 

  50. Gouw AA, Seewann A, van der Flier WM et al (2011) Heterogeneity of small vessel disease: a systematic review of MRI and histopathology correlations. J Neurol Neurosurg Psychiatry 82:126–135

    PubMed  Google Scholar 

  51. Graves AB, van Duijn CM, Chandra V et al (1991) Alcohol and tobacco consumption as risk factors for Alzheimer’s disease: a collaborative re-analysis of case–control studies. EURODEM Risk Factors Research Group. Int J Epidemiol 20 (Suppl 2):S48–S57

    PubMed  Google Scholar 

  52. Hawkins BT, Abbruscato TJ, Egleton RD et al (2004) Nicotine increases in vivo blood-brain barrier permeability and alters cerebral microvascular tight junction protein distribution. Brain Res 1027:48–58

    CAS  PubMed  Google Scholar 

  53. Hebert LE, Scherr PA, Beckett LA et al (1992) Relation of smoking and alcohol consumption to incident Alzheimer’s disease. Am J Epidemiol 135:347–355

    CAS  PubMed  Google Scholar 

  54. Hedberg MM, Svedberg MM, Mustafiz T et al (2008) Transgenic mice overexpressing human acetylcholinesterase and the Swedish amyloid precursor protein mutation: effect of nicotine treatment. Neuroscience 152:223–233

    CAS  PubMed  Google Scholar 

  55. Hellstrom-Lindahl E, Moore H, Nordberg A (2000) Increased levels of tau protein in SH-SY5Y cells after treatment with cholinesterase inhibitors and nicotinic agonists. J Neurochem 74:777–784

    CAS  PubMed  Google Scholar 

  56. Hellstrom-Lindahl E, Mousavi M, Ravid R, Nordberg A (2004) Reduced levels of Abeta 40 and Abeta 42 in brains of smoking controls and Alzheimer’s patients. Neurobiol Dis 15:351–360

    CAS  PubMed  Google Scholar 

  57. Heyman A, Wilkinson WE, Stafford JA, Helms MJ, Sigmon AH, Weinberg T (1984) Alzheimer’s disease: a study of epidemiological aspects. Ann Neurol 15:335–341

    CAS  PubMed  Google Scholar 

  58. Ho YS, Yang X, Yeung SC et al (2012) Cigarette smoking accelerated brain aging and induced pre-Alzheimer-like neuropathology in rats. PLoS One 7:e36752

    CAS  PubMed Central  PubMed  Google Scholar 

  59. Hong DP, Fink AL, Uversky VN (2009) Smoking and Parkinson’s disease: does nicotine affect alpha-synuclein fibrillation? Biochim Biophys Acta 1794:282–290

    CAS  PubMed Central  PubMed  Google Scholar 

  60. Hossain M, Sathe T, Fazio V et al (2009) Tobacco smoke: a critical etiological factor for vascular impairment at the blood-brain barrier. Brain Res 1287:192–205

    CAS  PubMed Central  PubMed  Google Scholar 

  61. Huang LH, He JY, Yuan BX, Cao YX (2010) Lipid soluble smoke particles upregulate endothelin receptors in rat basilar artery. Toxicol Lett 197:243–255

    CAS  PubMed  Google Scholar 

  62. Huang SH, Wang L, Chi F et al (2013) Circulating brain microvascular endothelial cells (cBMECs) as potential biomarkers of the blood–brain barrier disorders caused by microbial and non-microbial factors. PLoS One 8:e62164

    CAS  PubMed Central  PubMed  Google Scholar 

  63. Hung CH, Ho YS, Chang RCC (2010) Modulation of mitochondrial calcium as a pharmacological target for Alzheimer’s disease. Ageing Res Rev 9:447–456

    CAS  PubMed  Google Scholar 

  64. Jackson CA, Hutchison A, Dennis MSATAL (2010) Differing risk factor profiles of ischemic stroke subtypes: evidence for a distinct lacunar arteriopathy? Stroke 41:624–629

    PubMed  Google Scholar 

  65. Jacobsen LK, Picciotto MR, Heath CJ et al (2007) Prenatal and adolescent exposure to tobacco smoke modulates the development of white matter microstructure. J Neurosci 27:13491–13498

    CAS  PubMed  Google Scholar 

  66. Jayaraman T, Paget A, Shin YS et al (2008) TNF-alpha-mediated inflammation in cerebral aneurysms: a potential link to growth and rupture. Vasc Health Risk Manag 4:805–817

    CAS  PubMed Central  PubMed  Google Scholar 

  67. Kable JA, Coles CD, Lynch ME, Carroll J (2009) The impact of maternal smoking on fast auditory brainstem responses. Neurotoxicol Teratol 31:216–224

    CAS  PubMed Central  PubMed  Google Scholar 

  68. Kallen K (2000) Maternal smoking during pregnancy and infant head circumference at birth. Early Hum Dev 58:197–204

    CAS  PubMed  Google Scholar 

  69. Khan U, Porteous L, Hassan A, Markus H (2007) Risk factor profile of cerebral small vessel disease and its subtypes. J Neurol Neurosurg Psychiatry 78:702–706

    PubMed  Google Scholar 

  70. Khanna A, Guo M, Mehra M, Royal W (2013) Inflammation and oxidative stress induced by cigarette smoke in Lewis rat brains. J Neuroimmunol 254:69–75

    CAS  PubMed  Google Scholar 

  71. Kim SH, Kim JS, Shin HS, Keen CL (2003) Influence of smoking on markers of oxidative stress and serum mineral concentrations in teenage girls in Korea. Nutrition 19:240–243

    CAS  PubMed  Google Scholar 

  72. Kitada K, Ohkita M, Matsumura Y (2012) Pathological importance of the endothelin-1/ET(B) receptor system on vascular diseases. Cardiol Res Pract 2012:731970

    PubMed Central  PubMed  Google Scholar 

  73. Lambe M, Hultman C, Torrang A, Maccabe J, Cnattingius S (2006) Maternal smoking during pregnancy and school performance at age 15. Epidemiology 17:524–530

    PubMed  Google Scholar 

  74. Lau WK, Mak JC, Chan KH, Law AC (2012) Cigarette smoke-induced cerebral cortical interleukin-6 elevation is not mediated through oxidative stress. Neurotox Res 22:170–176

    CAS  PubMed Central  PubMed  Google Scholar 

  75. Lin F, Wu G, Zhu L, Lei H (2013) Heavy smokers show abnormal microstructural integrity in the anterior corpus callosum: a diffusion tensor imaging study with tract-based spatial statistics. Drug Alcohol Depend 129:82–87

    CAS  PubMed  Google Scholar 

  76. Lindley AA, Becker S, Gray RH, Herman AA (2000) Effect of continuing or stopping smoking during pregnancy on infant birth weight, crown-heel length, head circumference, ponderal index, and brain:body weight ratio. Am J Epidemiol 152:219–225

    CAS  PubMed  Google Scholar 

  77. Liu J, Lester BM, Neyzi N et al (2013) Regional brain morphometry and impulsivity in adolescents following prenatal exposure to cocaine and tobacco. JAMA Pediatr 167:348–354

    PubMed  Google Scholar 

  78. Liu Q, Zhang J, Zhu H, Qin C, Chen Q, Zhao B (2007) Dissecting the signaling pathway of nicotine-mediated neuroprotection in a mouse Alzheimer disease model. FASEB J 21:61–73

    CAS  PubMed  Google Scholar 

  79. McCartney JS, Fried PA, Watkinson B (1994) Central auditory processing in school-age children prenatally exposed to cigarette smoke. Neurotoxicol Teratol 16:269–276

    CAS  PubMed  Google Scholar 

  80. Middleton FA, Strick PL (2001) Cerebellar projections to the prefrontal cortex of the primate. J Neurosci 21:700–712

    CAS  PubMed  Google Scholar 

  81. Miller AH, Maletic V, Raison CL (2009) Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry 65:732–741

    CAS  PubMed Central  PubMed  Google Scholar 

  82. Miyake Y, Tanaka K, Fukushima W et al (2012) SNCA polymorphisms, smoking, and sporadic Parkinson’s disease in Japanese. Parkinsonism Relat Disord 18:557–561

    PubMed  Google Scholar 

  83. Miyao M, Furuta M, Matsushita Y, Ogiso M, Ishihara S, Teo PC (1995) A matched-pair longitudinal study on the relationship between maternal smoking and head circumference of newborns. Tohoku J Exp Med 175:135–137

    CAS  PubMed  Google Scholar 

  84. Moreno-Gonzalez I, Estrada LD, Sanchez-Mejias E, Soto C (2013) Smoking exacerbates amyloid pathology in a mouse model of Alzheimer’s disease. Nat Commun 4:1495

    PubMed  Google Scholar 

  85. Mousavi M, Hellstrom-Lindahl E (2009) Nicotinic receptor agonists and antagonists increase sAPPalpha secretion and decrease Abeta levels in vitro. Neurochem Int 54:237–244

    CAS  PubMed  Google Scholar 

  86. Mouton-Liger F, Paquet C, Dumurgier J et al (2012) Oxidative stress increases BACE1 protein levels through activation of the PKR-eIF2alpha pathway. Biochim Biophys Acta 1822:885–896

    CAS  PubMed  Google Scholar 

  87. Newby AC (2007) Metalloproteinases and vulnerable atherosclerotic plaques. Trends Cardiovasc Med 17:253–258

    CAS  PubMed Central  PubMed  Google Scholar 

  88. Nie HZ, Li ZQ, Yan QX et al (2011) Nicotine decreases beta-amyloid through regulating BACE1 transcription in SH-EP1-alpha4beta2 nAChR-APP695 cells. Neurochem Res 36:904–912

    CAS  PubMed  Google Scholar 

  89. O’Callaghan FV, Al MA, O’Callaghan M, Alati R, Williams GM, Najman JM (2010) Is smoking in pregnancy an independent predictor of academic difficulties at 14 years of age? A birth cohort study. Early Hum Dev 86:71–76

    PubMed  Google Scholar 

  90. O’Donnell MJ, Xavier D, Liu L et al (2010) Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study): a case–control study. Lancet 376:112–123

    PubMed  Google Scholar 

  91. Oddo S, Caccamo A, Green KN (2005) Chronic nicotine administration exacerbates tau pathology in a transgenic model of Alzheimer’s disease. Proc Natl Acad Sci USA 102:3046–3051

    CAS  PubMed  Google Scholar 

  92. Ogata J, Yamanishi H, Ishibashi-Ueda H (2011) Review: role of cerebral vessels in ischaemic injury of the brain. Neuropathol Appl Neurobiol 37:40–55

    CAS  PubMed  Google Scholar 

  93. Ono K, Hasegawa K, Yamada M, Naiki H (2002) Nicotine breaks down preformed Alzheimer’s beta-amyloid fibrils in vitro. Biol Psychiatry 52:880–886

    CAS  PubMed  Google Scholar 

  94. Orejana L, Barros-Minones L, Aguirre N, Puerta E (2013) Implication of JNK pathway on tau pathology and cognitive decline in a senescence-accelerated mouse model. Exp Gerontol 48:565–571

    CAS  PubMed  Google Scholar 

  95. Pan P, Shi H, Zhong J, Xiao P, Shen Y, Wu L, Song Y, He G (2012) Chronic smoking and brain gray matter changes: evidence from meta-analysis of voxel-based morphometry studies. Neurol Sci 34:813–817

    PubMed  Google Scholar 

  96. Pantoni L (2010) Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol 9:689–701

    PubMed  Google Scholar 

  97. Paulson JR, Roder KE, McAfee G, Allen DD, Van der Schyf CJ, Abbruscato TJ (2006) Tobacco smoke chemicals attenuate brain-to-blood potassium transport mediated by the Na, K, 2Cl-cotransporter during hypoxia-reoxygenation. J Pharmacol Exp Ther 316:248–254

    CAS  PubMed  Google Scholar 

  98. Paulson JR, Yang T, Selvaraj PK et al (2010) Nicotine exacerbates brain edema during in vitro and in vivo focal ischemic conditions. J Pharmacol Exp Ther 332:371–379

    CAS  PubMed  Google Scholar 

  99. Paus T, Nawazkhan I, Leonard G et al (2008) Corpus callosum in adolescent offspring exposed prenatally to maternal cigarette smoking. Neuroimage 40:435–441

    CAS  PubMed  Google Scholar 

  100. Peck JD, Neas B, Robledo C, Saffer E, Beebe L, Wild RA (2010) Intrauterine tobacco exposure may alter auditory brainstem responses in newborns. Acta Obstet Gynecol Scand 89(4):592–596

    CAS  PubMed  Google Scholar 

  101. Peterson BS, Vohr B, Staib LH et al (2000) Regional brain volume abnormalities and long-term cognitive outcome in preterm infants. JAMA 284:1939–1947

    CAS  PubMed  Google Scholar 

  102. Peterson J, Taylor HG, Minich N, Klein N, Hack M (2006) Subnormal head circumference in very low birth weight children: neonatal correlates and school-age consequences. Early Hum Dev 82:325–334

    PubMed  Google Scholar 

  103. Qi XL, Zhang XL, Ou-Yang K, Shan KR, Guan ZZ (2013) The influence of inhibiting or stimulating the expression of the alpha3 subunit of the nicotinic receptor in SH-SY5Y cells on levels of amyloid-beta peptide and beta-secretase. Neurochem Int 62:79–83

    CAS  PubMed  Google Scholar 

  104. Quik M (2004) Smoking, nicotine and Parkinson’s disease. Trends Neurosci 27:561–568

    CAS  PubMed  Google Scholar 

  105. Quik M, Perez XA, Bordia T (2012) Nicotine as a potential neuroprotective agent for Parkinson’s disease. Mov Disord 27:947–957

    CAS  PubMed Central  PubMed  Google Scholar 

  106. Quiroz-Baez R, Rojas E, Arias C (2009) Oxidative stress promotes JNK-dependent amyloidogenic processing of normally expressed human APP by differential modification of alpha-, beta- and gamma-secretase expression. Neurochem Int 55:662–670

    CAS  PubMed  Google Scholar 

  107. Rao JS, Kim HW, Harry GJ, Rapoport SI, Reese EA (2013) Increased neuroinflammatory and arachidonic acid cascade markers, and reduced synaptic proteins, in the postmortem frontal cortex from schizophrenia patients. Schizophr Res 147:24–31

    PubMed  Google Scholar 

  108. Rivkin MJ, Davis PE, Lemaster JL et al (2008) Volumetric MRI study of brain in children with intrauterine exposure to cocaine, alcohol, tobacco, and marijuana. Pediatrics 121:741–750

    PubMed Central  PubMed  Google Scholar 

  109. Roy TS, Sabherwal U (1994) Effects of prenatal nicotine exposure on the morphogenesis of somatosensory cortex. Neurotoxicol Teratol 16:411–421

    CAS  PubMed  Google Scholar 

  110. Roy TS, Sabherwal U (1998) Effects of gestational nicotine exposure on hippocampal morphology. Neurotoxicol Teratol 20:465–473

    CAS  PubMed  Google Scholar 

  111. Roy TS, Seidler FJ, Slotkin TA (2002) Prenatal nicotine exposure evokes alterations of cell structure in hippocampus and somatosensory cortex. J Pharmacol Exp Ther 300:124–133

    CAS  PubMed  Google Scholar 

  112. Roza SJ, Verburg BO, Jaddoe VW et al (2007) Effects of maternal smoking in pregnancy on prenatal brain development. The Generation R Study. Eur J Neurosci 25:611–617

    PubMed  Google Scholar 

  113. Salomon AR, Marcinowski KJ, Friedland RP, Zagorski MG (1996) Nicotine inhibits amyloid formation by the beta-peptide. Biochemistry 35:13568–13578

    CAS  PubMed  Google Scholar 

  114. Sandhu H, Xu CB, Edvinsson L (2010) Upregulation of contractile endothelin type B receptors by lipid-soluble cigarette smoking particles in rat cerebral arteries via activation of MAPK. Toxicol Appl Pharmacol 249:25–32

    CAS  PubMed  Google Scholar 

  115. Schreiber S, Bueche CZ, Garz C, Braun H (2013) Blood brain barrier breakdown as the starting point of cerebral small vessel disease?—New insights from a rat model. Exp Transl Stroke Med 5:4

    PubMed Central  PubMed  Google Scholar 

  116. Schwartz RS, Halliday GM, Cordato DJ, Kril JJ (2012) Small-vessel disease in patients with Parkinson’s disease: a clinicopathological study. Mov Disord 27:1506–1512

    PubMed  Google Scholar 

  117. Shen C, Chen Y, Liu H et al (2008) Hydrogen peroxide promotes Abeta production through JNK-dependent activation of gamma-secretase. J Biol Chem 283:17721–17730

    CAS  PubMed  Google Scholar 

  118. Sonnen JA, Larson EB, Gray SL et al (2009) Free radical damage to cerebral cortex in Alzheimer’s disease, microvascular brain injury, and smoking. Ann Neurol 65:226–229

    CAS  PubMed Central  PubMed  Google Scholar 

  119. Sowell ER, Thompson PM, Welcome SE, Henkenius AL, Toga AW, Peterson BS (2003) Cortical abnormalities in children and adolescents with attention-deficit hyperactivity disorder. Lancet 362:1699–1707

    PubMed  Google Scholar 

  120. Stene-Larsen K, Borge AI, Vollrath ME (2009) Maternal smoking in pregnancy and externalizing behavior in 18-month-old children: results from a population-based prospective study. J Am Acad Child Adolesc Psychiatry 48:283–289

    PubMed  Google Scholar 

  121. Stevenson SF, Doubal FN, Shuler K, Wardlaw JM (2010) A systematic review of dynamic cerebral and peripheral endothelial function in lacunar stroke versus controls. Stroke 41:e434–e442

    PubMed  Google Scholar 

  122. Topakian R, Barrick TR, Howe FA, Markus HS (2010) Blood-brain barrier permeability is increased in normal-appearing white matter in patients with lacunar stroke and leucoaraiosis. J Neurol Neurosurg Psychiatry 81:192–197

    CAS  PubMed  Google Scholar 

  123. Toro R, Leonard G, Lerner JV et al (2008) Prenatal exposure to maternal cigarette smoking and the adolescent cerebral cortex. Neuropsychopharmacology 33:1019–1027

    CAS  PubMed  Google Scholar 

  124. Tsuang D, Larson EB, Li G, Shofer JB, Montine KS, Thompson ML, Sonnen JA, Crane PK, Leverenz JB, Montine TJ (2010) Association between lifetime cigarette smoking and lewy body accumulation. Brain Pathol 20:412–418

    PubMed Central  PubMed  Google Scholar 

  125. Tyas SL, White LR, Petrovitch H et al (2003) Mid-life smoking and late-life dementia: the Honolulu-Asia Aging Study. Neurobiol Aging 24:589–596

    PubMed  Google Scholar 

  126. UK Department of Health (2012) Half of all smokers underestimate the health and financial impacts of smoking. 1-1-2012. Ref Type: Report

  127. Ulrich J, Johannson-Locher G, Seiler WO, Stahelin HB (1997) Does smoking protect from Alzheimer’s disease? Alzheimer-type changes in 301 unselected brains from patients with known smoking history. Acta Neuropathol 94:450–454

    CAS  PubMed  Google Scholar 

  128. van Dijk EJ, Prins ND, Vrooman HA, Hofman A, Koudstaal PJ, Breteler MM (2008) Progression of cerebral small vessel disease in relation to risk factors and cognitive consequences: Rotterdam Scan study. Stroke 39:2712–2719

    PubMed  Google Scholar 

  129. Vikman P, Xu CB, Edvinsson L (2009) Lipid-soluble cigarette smoking particles induce expression of inflammatory and extracellular-matrix-related genes in rat cerebral arteries. Vasc Health Risk Manag 5:333–341

    CAS  PubMed Central  PubMed  Google Scholar 

  130. Wang HY, Li W, Benedetti NJ, Lee DH (2003) Alpha 7 nicotinic acetylcholine receptors mediate beta-amyloid peptide-induced tau protein phosphorylation. J Biol Chem 278:31547–31553

    CAS  PubMed  Google Scholar 

  131. Wardlaw JM (2010) Blood–brain barrier and cerebral small vessel disease. J Neurol Sci 299:66–71

    CAS  PubMed  Google Scholar 

  132. Wardlaw JM, Doubal F, Armitage P, Chappell F, Carpenter T, Munoz MS, Farrall A, Sudlow C, Dennis M, Dhillon B (2009) Lacunar stroke is associated with diffuse blood-brain barrier dysfunction. Ann Neurol 65:194–202

    PubMed  Google Scholar 

  133. Wardlaw JM, Smith C, Dichgans M (2013) Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging. Lancet Neurol 12:483–497

    PubMed  Google Scholar 

  134. Wirdefeldt K, Adami HO, Cole P, Trichopoulos D, Mandel J (2011) Epidemiology and etiology of Parkinson’s disease: a review of the evidence. Eur J Epidemiol 26(Suppl 1):S1–S58

    PubMed  Google Scholar 

  135. World Health Organization (2011) Global status report on noncommunicable diseases 2010—Description of the gobal burden of NCDs, their risk factors and determinants. World Health Organization, editor. 1-31. 4-20-2011

  136. Xu CB, Zheng JP, Zhang W, Zhang Y, Edvinsson L (2008) Lipid-soluble smoke particles upregulate vascular smooth muscle ETB receptors via activation of mitogen-activating protein kinases and NF-kappaB pathways. Toxicol Sci 106:546–555

    CAS  PubMed  Google Scholar 

  137. Zhang JY, Cao YX, Xu CB, Edvinsson L (2006) Lipid-soluble smoke particles damage endothelial cells and reduce endothelium-dependent dilatation in rat and man. BMC Cardiovasc Disord 6:3

    PubMed Central  PubMed  Google Scholar 

  138. Zhang X, Salmeron BJ, Ross TJ, Geng X, Yang Y, Stein EA (2011) Factors underlying prefrontal and insula structural alterations in smokers. Neuroimage 54:42–48

    PubMed Central  PubMed  Google Scholar 

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Acknowledgments

The work in Laboratory of Neurodegenerative Diseases was supported by HKU Alzheimer’s Disease Research Network under Strategic Research Theme of Healthy Aging to RCCC. The work in Macau was supported by the Faculty Research Grant (0293) from MUST to YSH.

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Authors and Affiliations

  1. Laboratory of Neurodegenerative Diseases, Department of Anatomy, LKS Faculty of Medicine, The University of Hong Kong, Rm. L1-49, Laboratory Block, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong

    Raymond Chuen-Chung Chang

  2. State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Pokfulam, Hong Kong

    Raymond Chuen-Chung Chang

  3. Research Centre of Heart, Brain, Hormone and Healthy Aging, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong

    Raymond Chuen-Chung Chang

  4. State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau

    Yuen-Shan Ho

  5. Department of Pathology, Prince Margret Hospital, Kowloon, Hong Kong

    Shun Wong

  6. Neuropathology Unit, Department of Medicine, Imperial College London, London, UK

    Stephen M. Gentleman

  7. Department of Anatomical and Cellular Pathology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong

    Ho-Keung Ng

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  1. Raymond Chuen-Chung Chang
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  2. Yuen-Shan Ho
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  3. Shun Wong
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  4. Stephen M. Gentleman
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  5. Ho-Keung Ng
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Corresponding authors

Correspondence to Raymond Chuen-Chung Chang or Yuen-Shan Ho.

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Chang, R.CC., Ho, YS., Wong, S. et al. Neuropathology of cigarette smoking. Acta Neuropathol 127, 53–69 (2014). https://doi.org/10.1007/s00401-013-1210-x

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  • DOI: https://doi.org/10.1007/s00401-013-1210-x

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