Cytokine-mediated blood brain barrier disruption as a conduit for cancer/chemotherapy-associated neurotoxicity and cognitive dysfunction

International Journal of Cancer

Volumn 139, Issue 12, 2016, Pages 2635-2645

  Wardill, Hannah R ^a,b   Mander, Kimberley A ^a   Van Sebille, Ysabella Z A ^a   Gibson, Rachel J ^c   Logan, Richard M ^a   Bowen, Joanne M ^a   Sonis, Stephen T ^d,e  

^a UNIVERSITY OF ADELAIDE   (Australia)

^b SOUTH AUSTRALIAN HEALTH AND MEDICAL RESEARCH INSTITUTE   (Australia)

^c UNIVERSITY OF SOUTH AUSTRALIA   (Australia)

^d BRIGHAM AND WOMEN S HOSPITAL   (United States)

^e Biomodels   (United States)

Author keywords

blood brain barrier; chemotherapy induced gut toxicity; cognitive dysfunction; inflammation; neurotoxicity

Indexed keywords

ANTINEOPLASTIC AGENT; CYTOKINE; AUTACOID;

BLOOD BRAIN BARRIER; CANCER CHEMOTHERAPY; CHRONICITY; COGNITIVE DEFECT; CYTOKINE PRODUCTION; DIFFUSION TENSOR IMAGING; ENTERITIS; FUNCTIONAL MAGNETIC RESONANCE IMAGING; HUMAN; MALIGNANT NEOPLASTIC DISEASE; NERVOUS SYSTEM INFLAMMATION; NEUROIMAGING; NEUROPATHOLOGY; NEUROTOXICITY; NONHUMAN; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; REVIEW; VOXEL BASED MORPHOMETRY; ANIMAL; BRAIN; COGNITIVE DYSFUNCTION; COMPLICATION; DRUG EFFECTS; IMMUNOLOGY; INFLAMMATION; METABOLISM; NEOPLASMS; PATHOLOGY; PATHOPHYSIOLOGY; PHENOTYPE; PROCEDURES; TIGHT JUNCTION;

ANIMALS; ANTINEOPLASTIC AGENTS; BLOOD-BRAIN BARRIER; BRAIN; COGNITIVE DYSFUNCTION; CYTOKINES; HUMANS; INFLAMMATION; INFLAMMATION MEDIATORS; NEOPLASMS; NEUROIMAGING; PHENOTYPE; TIGHT JUNCTIONS;

EID: 84978371840     PISSN: 00207136     EISSN: 10970215     Source Type: Journal    
DOI: 10.1002/ijc.30252     Document Type: Review

References (121)

1. Holmes D. Trying to unravel the mysteries of chemobrain. Lancet Neurol 2013;12:533–4.
2. Ahles TA, Saykin AJ, McDonald BC, et al. Longitudinal assessment of cognitive changes associated with adjuvant treatment for breast cancer: impact of age and cognitive reserve. J Clin Oncol 2010;28:4434–40.
3. Jenkins V, Beveridge H, Low R, et al. Atypical hearing loss in women with breast cancer receiving adjuvant treatment. Breast 2006;15:448–51.
4. Jenkins V, Shilling V, Deutsch G, et al. A 3-year prospective study of the effects of adjuvant treatments on cognition in women with early stage breast cancer. Br J Cancer 2006;94:828–34.
5. Dietrich J, Prust M, Kaiser J. Chemotherapy, cognitive impairment and hippocampal toxicity. Neuroscience 2015;309:224–32.
6. Horky LL, Gerbaudo VH, Zaitsev A, et al. Systemic chemotherapy decreases brain glucose metabolism. Ann Clin Transl Neurol 2014;1:788–98.
7. Janelsins MC, Kohli S, Mohile SG, et al. An update on cancer- and chemotherapy-related cognitive dysfunction: current status. Semin Oncol 2011;38:431–8.
8. Wu LM, Diefenbach MA, Gordon WA, et al. Cognitive problems in patients on androgen deprivation therapy: a qualitative pilot study. Urol Oncol 2013;31:1533–8.
9. Sodeck GH, Domanovits H, Sterz F, et al. Can brain natriuretic peptide predict outcome after cardiac arrest? An observational study. Resuscitation 2007;74:439–45.
10. Tannock IF, Ahles TA, Ganz PA, et al. Cognitive impairment associated with chemotherapy for cancer: report of a workshop. J Clin Oncol 2004;22:2233–9.
11. Ahles TA, Saykin AJ. Candidate mechanisms for chemotherapy-induced cognitive changes. Nat Rev Cancer 2007;7:192–201.
12. Komaki R, Meyers CA, Shin DM, et al. Evaluation of cognitive function in patients with limited small cell lung cancer prior to and shortly following prophylactic cranial irradiation. Int J Radiat Oncol Biol Phys 1995;33:179–82.
13. Vardy JL, Dhillon HM, Pond GR, et al. Cognitive function in patients with colorectal cancer who do and do not receive chemotherapy: a prospective, longitudinal, controlled study. J Clin Oncol 2015;33:4085–92.
14. Bourke RS, West CR, Chheda G, et al. Kinetics of entry and distribution of 5-fluorouracil in cerebrospinal fluid and brain following intravenous injection in a primate. Cancer Res 1973;33:1735–46.
15. Brown MS, Simon JH, Stemmer SM, et al. MR and proton spectroscopy of white matter disease induced by high-dose chemotherapy with bone marrow transplant in advanced breast carcinoma. AJNR Am J Neuroradiol 1995;16:2013–20.
16. Brown MS, Stemmer SM, Simon JH, et al. White matter disease induced by high-dose chemotherapy: longitudinal study with MR imaging and proton spectroscopy. AJNR Am J Neuroradiol 1998;19:217–21.
17. Ferguson RJ, McDonald BC, Saykin AJ, et al. Brain structure and function differences in monozygotic twins: possible effects of breast cancer chemotherapy. J Clin Oncol 2007;25:3866–70.
18. Simo M, Rifa-Ros X, Rodriguez-Fornells A, et al. Chemobrain: a systematic review of structural and functional neuroimaging studies. Neurosci Biobehav Rev 2013;37:1311–21.
19. Ashburner J, Friston KJ. Voxel-based morphometry—the methods. Neuroimage 2000;11:805–21.
20. Ahdieh M, Vandenbos T, Youakim A. Lung epithelial barrier function and wound healing are decreased by IL-4 and IL-13 and enhanced by IFN-gamma. Am J Physiol Cell Physiol 2001;281:C2029–38.
21. Inagaki M, Yoshikawa E, Matsuoka Y, et al. Smaller regional volumes of brain gray and white matter demonstrated in breast cancer survivors exposed to adjuvant chemotherapy. Cancer 2007;109:146–56.
22. McDonald BC, Conroy SK, Ahles TA, et al. Gray matter reduction associated with systemic chemotherapy for breast cancer: a prospective MRI study. Breast Cancer Res Treat 2010;123:819–28.
23. Dietrich J, Monje M, Wefel J, et al. Clinical patterns and biological correlates of cognitive dysfunction associated with cancer therapy. Oncologist 2008;13:1285–95.
24. Nokia MS, Anderson ML, Shors TJ. Chemotherapy disrupts learning, neurogenesis and theta activity in the adult brain. Eur J Neurosci 2012;36:3521–30.
25. Han R, Yang YM, Dietrich J, et al. Systemic 5-fluorouracil treatment causes a syndrome of delayed myelin destruction in the central nervous system. J Biol 2008;7:12
26. Seigers R, Loos M, Van Tellingen O, et al. Neurobiological changes by cytotoxic agents in mice. Behav Brain Res 2015;299:19–26.
27. Abraham J, Haut MW, Moran MT, et al. Adjuvant chemotherapy for breast cancer: effects on cerebral white matter seen in diffusion tensor imaging. Clin Breast Cancer 2008;8:88–91.
28. Deprez S, Amant F, Yigit R, et al. Chemotherapy-induced structural changes in cerebral white matter and its correlation with impaired cognitive functioning in breast cancer patients. Hum Brain Mapp 2011;32:480–93.
29. Deprez S, Amant F, Smeets A, et al. Longitudinal assessment of chemotherapy-induced structural changes in cerebral white matter and its correlation with impaired cognitive functioning. J Clin Oncol 2012;30:274–81.
30. Ginos JZ, Cooper AJ, Dhawan V, et al. [13N]cisplatin PET to assess pharmacokinetics of intra-arterial versus intravenous chemotherapy for malignant brain tumors. J Nucl Med 1987;28:1844–52.
31. Gangloff A, Hsueh WA, Kesner AL, et al. Estimation of paclitaxel biodistribution and uptake in human-derived xenografts in vivo with (18)F-fluoropaclitaxel. J Nucl Med 2005;46:1866–71.
32. Dietrich J, Han R, Yang Y, et al. CNS progenitor cells and oligodendrocytes are targets of chemotherapeutic agents in vitro and in vivo. J Biol 2006;5:22
33. Rochfort KD, Collins LE, Murphy RP, et al. Downregulation of blood-brain barrier phenotype by proinflammatory cytokines involves NADPH oxidase-dependent ROS generation: consequences for interendothelial adherens and tight junctions. PLoS One 2014;9:e101815
34. Wardill HR, Bowen JM, Gibson RJ. Chemotherapy-induced gut toxicity: are alterations to intestinal tight junctions pivotal? Cancer Chemother Pharmacol 2012;70:627–35.
35. Corps KN, Roth TL, McGavern DB. Inflammation and neuroprotection in traumatic brain injury. JAMA Neurol 2015;72:355–62.
36. Chodobski A, Zink BJ, Szmydynger-Chodobska J. Blood-brain barrier pathophysiology in traumatic brain injury. Transl Stroke Res 2011;2:492–516.
37. Jickling GC, Liu D, Stamova B, et al. Hemorrhagic transformation after ischemic stroke in animals and humans. J Cereb Blood Flow Metab 2014;34:185–99.
38. Al-Dasooqi N, Gibson RJ, Bowen JM, et al. Matrix metalloproteinases are possible mediators for the development of alimentary tract mucositis in the dark agouti rat. Exp Biol Med 2010;235:1244–56.
39. Cummins PM. Occludin: one protein, many forms. Mol Cell Biol 2012;32:242–50.
40. Bauer A, Burgers H, Rabie T, et al. Matrix metalloproteinase-9 mediates hypoxia-induced vascular leakage in the brain via tight junction rearrangement. J Cereb Blood Flow Metab 2010;30:837–48.
41. Lischper M, Beuck S, Thanabalasundaram G, et al. Metalloproteinase mediated occludin cleavage in the cerebral microcapillary endothelium under pathological conditions. Brain Res 2010;1326:114–27.
42. Vermeer P, Denker J, Estin M, et al. MMP9 modulates tight junction integrity and cell viability in human airway epithelia. Am J Physiol Lung Cell Mol Physiol 2009;296:L751–62.
43. Liu W, Hendren J, Qin X, et al. Normobaric hyperoxia attenuates early blood-brain barrier disruption by inhibiting MMP-9-mediated occludin degradation in focal cerebral ischemia. J Neurochem 2009;108:811–20.
44. Chen W, et al. Matrix metalloproteinases inhibition provides neuroprotection against hypoxia-ischemia in the developing brain. J Neurochem 2009;111:726–36.
45. Higashida T, et al. The role of hypoxia-inducible factor-1alpha, aquaporin-4 and matrix metalloproteinase-9 in blood-brain barrier disruption and brain edema after traumatic brain injury. J Neurosurg 2011;114:92–101.
46. Asahi M, Wang X, Mori T, et al. Effects of matrix metalloproteinase-9 gene knock-out on the proteolysis of blood-brain barrier and white matter components after cerebral ischemia. J Neurosci 2001;21:7724–32.
47. de Vries HE, Kuiper J, de Boer AG, et al. The blood-brain barrier in neuroinflammatory diseases. Pharmacol Rev 1997;49:143–55.
48. Blanco AM, Perez-Arago A, Fernandez-Lizarbe S, et al. Ethanol mimics ligand-mediated activation and endocytosis of IL-1RI/TLR4 receptors via lipid rafts caveolae in astroglial cells. J Neurochem 2008;106:625–39.
49. Pan W, Stone KP, Hsuchou H, et al. Cytokine signaling modulates blood-brain barrier function. Curr Pharm Des 2011;17:3729–40.
50. Pan W, Tu H, Yu C, et al. Differential role of TNF receptors in cellular trafficking of intact TNF. Cell Physiol Biochem 2007;20:559–68.
51. Logan RM, Gibson RJ, Bowen JM, et al. Characterisation of mucosal changes in the alimentary tract following administration of irinotecan: implications for the pathobiology of mucositis. Cancer Chemother Pharmacol 2008;62:33–41.
52. Logan RM, Stringer AM, Bowen JM, et al. The role of pro-inflammatory cytokines in cancer treatment-induced alimentary tract mucositis: pathobiology, animal models and cytotoxic drugs. Cancer Treat Rev 2007;33:448–60.
53. Sonis ST. Mucositis as a biological process: a new hypothesis for the development of chemotherapy-induced stomatotoxicity. Oral Oncol 1998;34:39–43.
54. Papadakis KA, Targan SR. Role of cytokines in the pathogenesis of inflammatory bowel disease. Ann Rev Med 2000;51:289–98.
55. Galvez BG, Matias-Roman S, Yanez-Mo M, et al. Caveolae are a novel pathway for membrane-type 1 matrix metalloproteinase traffic in human endothelial cells. Mol Biol Cell 2004;15:678–87.
56. Wardill HR, Bowen JM, Al-Dasooqi N, et al. Irinotecan disrupts tight junction proteins within the gut: implications for chemotherapy-induced gut toxicity. Cancer Biol Ther 2014;15:236–44.
57. Al-Dasooqi N, Sonis ST, Bowen JM, et al. Emerging evidence on the pathobiology of mucositis. Supp Care Cancer 2013;21:3233–41.
58. Al-Dasooqi N, Sonis ST, Bowen JM, et al. Emerging evidence on the pathobiology of mucositis. Supp Care Cancer 2013;21:2075–83.
59. Stringer AM, Al-Dasooqi N, Bowen JM, et al. Biomarkers of chemotherapy-induced diarrhoea: a clinical study of intestinal microbiome alterations, inflammation and circulating matrix metalloproteinases. Supp Care Cancer 2013;21:1843–52.
60. Schreibelt G, Kooij G, Reijerkerk A, et al. Reactive oxygen species alter brain endothelial tight junction dynamics via RhoA, PI3 kinase, and PKB signaling. FASEB J 2007;21:3666–76.
61. Henriksen EJ. A radical concept on caveolae and endothelial dysfunction in coronary microvascular disease in diabetes. Diabetes 2014;63:1200–2.
62. Chidlow JH, Jr, Sessa WC. Caveolae, caveolins, and cavins: complex control of cellular signalling and inflammation. Cardiovasc Res 2010;86:219–25.
63. Stringer AM. Interaction between host cells and microbes in chemotherapy-induced mucositis. Nutrients 2013;5:1488–99.
64. Sharma R, Young C, Neu J. Molecular modulation of intestinal epithelial barrier: contribution of microbiota. J Biomed Biotechnol 2010;2010:305879
65. Sharma HS, Vannemreddy P, Patnaik R, et al. Histamine receptors influence blood-spinal cord barrier permeability, edema formation, and spinal cord blood flow following trauma to the rat spinal cord. Acta Neurochir Suppl 2006;96:316–21.
66. Rodriguez PL, Jiang S, Fu Y, et al. The proinflammatory peptide substance P promotes blood-brain barrier breaching by breast cancer cells through changes in microvascular endothelial cell tight junctions. Int J Cancer 2014;134:1034–44.
67. Vink R, van den Heuvel C. Substance P antagonists as a therapeutic approach to improving outcome following traumatic brain injury. Neurotherapeutics 2010;7:74–80.
68. D'Alessio A, Al-Lamki RS, Bradley JR, et al. Caveolae participate in tumor necrosis factor receptor 1 signaling and internalization in a human endothelial cell line. Am J Pathol 2005;166:1273–82.
69. Mustian KM, Devine K, Ryan JL, et al. Treatment of nausea and vomiting during chemotherapy. US Oncol Hematol 2011;7:91–7.
70. Wardill HR, Gibson RJ, Logan RM, et al. TLR4/PKC-mediated tight junction modulation: a clinical marker of chemotherapy-induced gut toxicity? Int J Cancer 2013;135:2483–92.
71. Jiao H, Zhang Y, Yan Z, et al. Caveolin-1 Tyr14 phosphorylation induces interaction with TLR4 in endothelial cells and mediates MyD88-dependent signaling and sepsis-induced lung inflammation. J Immunol 2013;191:6191–9.
72. Villena J, Kitazawa H. Modulation of intestinal TLR4-inflammatory signaling pathways by probiotic microorganisms: lessons learned from lactobacillus jensenii TL2937. Front Immunol 2014;4:512
73. Argaw AT, Asp L, Zhang J, et al. Astrocyte-derived VEGF-A drives blood-brain barrier disruption in CNS inflammatory disease. J Clin Invest 2012;122:2454–68.
74. Argaw AT, Gurfein BT, Zhang Y, et al. VEGF-mediated disruption of endothelial CLN-5 promotes blood-brain barrier breakdown. Proc Natl Acad Sci U S A 2009;106:1977–82.
75. Proescholdt MA, Jacobson S, Tresser N, et al. Vascular endothelial growth factor is expressed in multiple sclerosis plaques and can induce inflammatory lesions in experimental allergic encephalomyelitis rats. J Neuropathol Exp Neurol 2002;61:914–25.
76. Caliceti C, Zambonin L, Rizzo B, et al. Role of plasma membrane caveolae/lipid rafts in VEGF-induced redox signaling in human leukemia cells. BioMed Res Int 2014;2014:857504
77. Boussios S, Pentheroudakis G, Katsanos K, et al. Systemic treatment-induced gastrointestinal toxicity: incidence, clinical presentation and management. Ann Gastroenterol 2012;25:106–18.
78. Seigers R, Fardell JE. Neurobiological basis of chemotherapy-induced cognitive impairment: a review of rodent research. Neurosci Biobehav Rev 2011;35:729–41.
79. Wardill HR, Van Sebille YZ, Mander KA, et al. Toll-like receptor 4 signaling: a common biological mechanism of regimen-related toxicities: an emerging hypothesis for neuropathy and gastrointestinal toxicity. Cancer Treat Rev 2015;41:122–8.
80. Wardill HR, Gibson RJ, Van Sebille YZ, et al. Irinotecan-induced gastrointestinal dysfunction and pain are mediated by common TLR4-dependent mechanisms. Mol Cancer Ther 201615:1376–86.
81. Bowen JM, Coller J, Hutchinson M, et al. Expression of TLRs in the rat intestine following chemotherapy for cancer. Brain Behav Immun 2012;26:S27–S
82. Wong DV, Lima-Junior RC, Carvalho CB, et al. The adaptor protein Myd88 is a key signaling molecule in the pathogenesis of irinotecan-induced intestinal mucositis. PloS One 2015;10:e0139985
83. Frank M, Hennenberg EM, Eyking A, et al. TLR signaling modulates side effects of anticancer therapy in the small intestine. J Immunol 2015;194:1983–95.
84. Wardill HR, Gibson RJ, Logan RM, et al. TLR4/PKC-mediated tight junction modulation: a clinical marker of chemotherapy-induced gut toxicity? Int J Cancer 2014;135:2483–92.
85. Guo S, Nighot M, Al-Sadi R, Alhmoud T, Nighot P, Ma TY. Lipopolysaccharide Regulation of Intestinal Tight Junction Permeability Is Mediated by TLR4 Signal Transduction Pathway Activation of FAK and MyD88. J Immunol. 2015;195:4999–5010
86. Li X, Wang C, Nie J, et al. Toll-like receptor 4 increases intestinal permeability through up-regulation of membrane PKC activity in alcoholic steatohepatitis. Alcohol 2013;47:459–65.
87. Nyuyki KD, Pittman QJ. Toward a better understanding of the central consequences of intestinal inflammation. Ann N Y Acad Sci 2015;1351:149–54.
88. Brown KA, Back SJ, Ruchelli ED, et al. Lamina propria and circulating interleukin-6 in newly diagnosed pediatric inflammatory bowel disease patients. Am J Gastroenterol 2002;97:2603–8.
89. Natah SS, Mouihate A, Pittman QJ, et al. Disruption of the blood-brain barrier during TNBS colitis. Neurogastroenterol Motility 2005;17:433–46.
90. Wang K, Yuan CP, Wang W, et al. Expression of interleukin 6 in brain and colon of rats with TNBS-induced colitis. World J Gastroenterol 2010;16:2252–9.
91. Riazi K, Galic MA, Kuzmiski JB, et al. Microglial activation and TNFalpha production mediate altered CNS excitability following peripheral inflammation. Proc Natl Acad Sci U S A 2008;105:17151–6.
92. Zonis S, Pechnick RN, Ljubimov VA, et al. Chronic intestinal inflammation alters hippocampal neurogenesis. J Neuroinflammation 2015;12:65
93. Bercik P, Verdu EF, Foster JA, et al. Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry in mice. Gastroenterology 2010;139:2102–12 e1.
94. Goehler LE, Gaykema RP, Opitz N, et al. Activation in vagal afferents and central autonomic pathways: early responses to intestinal infection with Campylobacter jejuni. Brain Behav Immun 2005;19:334–44.
95. Dantzer R, O'Connor JC, Freund GG, et al. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 2008;9:46–56.
96. Gatti S, Bartfai T. Induction of tumor necrosis factor-alpha mRNA in the brain after peripheral endotoxin treatment: comparison with interleukin-1 family and interleukin-6. Brain Res 1993;624:291–4.
97. Laye S, Parnet P, Goujon E, et al. Peripheral administration of lipopolysaccharide induces the expression of cytokine transcripts in the brain and pituitary of mice. Brain Res Mol Brain Res 1994;27:157–62.
98. Quan N, Stern EL, Whiteside MB, et al. Induction of pro-inflammatory cytokine mRNAs in the brain after peripheral injection of subseptic doses of lipopolysaccharide in the rat. J Neuroimmunol 1999;93:72–80.
99. Holden JM, Overmier JB, Cowan ET, et al. Effects of lipopolysaccharide on consolidation of partial learning in the Y-maze. Integr Physiol Behav Sci 2004;39:334–40.
100. Gahtan E, Overmier JB. Performance more than working memory disrupted by acute systemic inflammation in rats in appetitive tasks. Physiol Behav 2001;73:201–10.
101. Sparkman NL, Buchanan JB, Heyen JR, et al. Interleukin-6 facilitates lipopolysaccharide-induced disruption in working memory and expression of other proinflammatory cytokines in hippocampal neuronal cell layers. J Neurosci 2006;26:10709–16.
102. Krabbe KS, Reichenberg A, Yirmiya R, et al. Low-dose endotoxemia and human neuropsychological functions. Brain Behav Immun 2005;19:453–60.
103. Krabbe KS, Pedersen M, Bruunsgaard H. Inflammatory mediators in the elderly. Exp Gerontol 2004;39:687–99.
104. Capuron L, Ravaud A, Dantzer R. Timing and specificity of the cognitive changes induced by interleukin-2 and interferon-alpha treatments in cancer patients. Psychosom Med 2001;63:376–86.
105. Trask PC, Esper P, Riba M, et al. Psychiatric side effects of interferon therapy: prevalence, proposed mechanisms, and future directions. J Clin Oncol 2000;18:2316–26.
106. Meyers CA, Albitar M, Estey E. Cognitive impairment, fatigue, and cytokine levels in patients with acute myelogenous leukemia or myelodysplastic syndrome. Cancer 2005;104:788–93.
107. Bower JE, Ganz PA, Aziz N, et al. Inflammatory responses to psychological stress in fatigued breast cancer survivors: relationship to glucocorticoids. Brain Behav Immun 2007;21:251–8.
108. Collado-Hidalgo A, Bower JE, Ganz PA, et al. Inflammatory biomarkers for persistent fatigue in breast cancer survivors. Clin Cancer Res 2006;12:2759–66.
109. Cheng X, Yang L, He P, et al. Differential activation of tumor necrosis factor receptors distinguishes between brains from Alzheimer's disease and non-demented patients. J Alzheimers Dis 2010;19:621–30.
110. Di Bona D, Candore G, Franceschi C, et al. Systematic review by meta-analyses on the possible role of TNF-alpha polymorphisms in association with Alzheimer's disease. Brain Res Rev 2009;61:60–8.
111. Minter MR, Taylor JM, Crack PJ. The contribution of neuro-inflammation to amyloid toxicity in Alzheimer's disease. J Neurochem 2015;136:457–74.
112. in't Veld BA, Launer LJ, Hoes AW, et al. NSAIDs and incident Alzheimer's disease. The Rotterdam Study. Neurobiol Aging 1998;19:607–11.
113. Alkam T, Nitta A, Mizoguchi H, et al. Restraining tumor necrosis factor-alpha by thalidomide prevents the amyloid beta-induced impairment of recognition memory in mice. Behav Brain Res 2008;189:100–6.
114. Sharma HS, Castellani RJ, Smith MA, et al. The blood-brain barrier in Alzheimer's disease: novel therapeutic targets and nanodrug delivery. Int Rev Neurobiol 2012;102:47–90.
115. Patel SK, Wong AL, Wong FL, et al. Inflammatory biomarkers, comorbidity, and neurocognition in women with newly diagnosed breast cancer. J Natl Cancer Inst 2015;107. doi: 10.1093/jnci/djv131.
116. Roque AT, Gambeloni RZ, Felitti S, et al. Inflammation-induced oxidative stress in breast cancer patients. Med Oncol 2015;32:263
117. Hjermstad M, Holte H, Evensen S, et al. Do patients who are treated with stem cell transplantation have a health-related quality of life comparable to the general population after 1 year? Bone Marrow Transplant 1999;24:911–8.
118. Genschaft M, Huebner T, Plessow F, et al. Impact of chemotherapy for childhood leukemia on brain morphology and function. PloS One 2013;8:e78599
119. McDonald BC, Conroy SK, Ahles TA, et al. Gray matter reduction associated with systemic chemotherapy for breast cancer: a prospective MRI study. Breast Cancer Res Treat 2010;123:819–28.
120. Lepage C, Smith AM, Moreau J, et al. A prospective study of grey matter and cognitive function alterations in chemotherapy-treated breast cancer patients. SpringerPlus 2014;3:444
121. Wardill HR, Van Sebille YZ, Mander KA, et al. Toll-like receptor 4 signaling: a common biological mechanism of regimen-related toxicities: an emerging hypothesis for neuropathy and gastrointestinal toxicity. Cancer Treat Rev 2015;41:122–8.