Neuroscience Bulletin

, Volume 34, Issue 6, pp 1058–1066 | Cite as

Cortical Inflammation is Increased in a DSS-Induced Colitis Mouse Model

  • Ying Han
  • Tong Zhao
  • Xiang Cheng
  • Ming Zhao
  • Sheng-Hui Gong
  • Yong-Qi Zhao
  • Hai-Tao Wu
  • Ming FanEmail author
  • Ling-Ling ZhuEmail author
Original Article


While inflammatory bowel disease (IBD) might be a risk factor in the development of brain dysfunctions, the underlying mechanisms are largely unknown. Here, mice were treated with 5% dextran sodium sulfate (DSS) in drinking water and sacrificed on day 7. The serum level of IL-6 increased, accompanied by elevation of the IL-6 and TNF-α levels in cortical tissue. However, the endotoxin concentration in plasma and brain of mice with DSS-induced colitis showed a rising trend, but with no significant difference. We also found significant activation of microglial cells and reduction in occludin and claudin-5 expression in the brain tissue after DSS-induced colitis. These results suggested that DSS-induced colitis increases systemic inflammation which then results in cortical inflammation via up-regulation of serum cytokines. Here, we provide new information on the impact of colitis on the outcomes of cortical inflammation.


Cortical inflammation Dextran sodium sulfate Colitis Endotoxin Blood-brain barrier 



We thank Prof. TM Zhang of Academy of Military Medical Sciences for helpful comments. This work was supported by grants from the National Natural Science Foundation of China (81430044) and the National Basic Research Development Program of China (2012CB518200 and 2011CB910800).

Compliance with Ethical Standards

Conflict of interest

The authors have no conflict of interest to declare

Supplementary material

12264_2018_288_MOESM1_ESM.pdf (1.4 mb)
Supplementary material 1 (PDF 1436 kb)


  1. 1.
    Hanauer SB. Inflammatory bowel disease: epidemiology, pathogenesis, and therapeutic opportunities. Inflamm Bowel Dis 2006, 12: S3–S9.CrossRefPubMedCentralGoogle Scholar
  2. 2.
    Sandler RS, Stewart WF, Liberman JN, Ricci JA, Zorich NL. Abdominal pain, bloating, and diarrheain the United States. Dig Dis Sci 2000, 45: 1166–1171.CrossRefPubMedCentralGoogle Scholar
  3. 3.
    Zonis S, Pechnick RN, Ljubimov VA, Mahgerefteh M, Wawrowsky K, Michelsen KS, et al. Chronic intestinal inflammation alters hippocampal neurogenesis. J Neuroinflammation 2015, 12: 65.CrossRefPubMedCentralGoogle Scholar
  4. 4.
    Kurina LM, Goldacre MJ, Yeates D, Gill LE. Depression and anxiety in people with inflammatory bowel disease. J Epidemiol Community Health 2001, 55: 716.CrossRefPubMedCentralGoogle Scholar
  5. 5.
    Villaran RF, Espinosa-Oliva AM, Sarmiento M, De Pablos RM, Arguelles S, Delgado-Cortes MJ, et al. Ulcerative colitis exacerbates lipopolysaccharide-induced damage to the nigral dopaminergic system: potential risk factor in Parkinson`s disease. J Neurochem 2010, 114: 1687–1700.CrossRefPubMedCentralGoogle Scholar
  6. 6.
    Yokoyama JS, Wang Y, Schork AJ, Thompson WK, Karch CM, Cruchaga C, et al. Association between genetic traits for immune-mediated diseases and Alzheimer disease. JAMA Neurol 2016, 73: 691.CrossRefPubMedCentralGoogle Scholar
  7. 7.
    Chen B, Girgis S, El-Matary W. Childhood autism and eosinophilic colitis. Digestion 2010, 81: 127–129.CrossRefPubMedCentralGoogle Scholar
  8. 8.
    Heberling CA, Dhurjati PS, Sasser M. Hypothesis for a systems connectivity model of Autism Spectrum Disorder pathogenesis: links to gut bacteria, oxidative stress, and intestinal permeability. Med Hypotheses 2013, 80: 264.CrossRefPubMedCentralGoogle Scholar
  9. 9.
    Riazi K, Galic MA, Kuzmiski JB, Ho W, Sharkey KA, Pittman QJ. Microglial activation and TNFalpha production mediate altered CNS excitability following peripheral inflammation. Proc Natl Acad Sci U S A 2008, 105: 17151–17156.CrossRefPubMedCentralGoogle Scholar
  10. 10.
    Raghavendra V, Tanga FY, Deleo JA. Complete Freunds adjuvant-induced peripheral inflammation evokes glial activation and proinflammatory cytokine expression in the CNS. Eur J Neurosci 2004, 20: 467.CrossRefPubMedCentralGoogle Scholar
  11. 11.
    Hathaway CA, Appleyard CB, Percy WH, Williams JL. Experimental colitis increases blood-brain barrier permeability in rabbits. Am J Physiol 1999, 276: G1174.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Engelhardt B, Sorokin L. The blood–brain and the blood–cerebrospinal fluid barriers: function and dysfunction. Semin Immunopathol 2009: 497–511.CrossRefPubMedCentralGoogle Scholar
  13. 13.
    Sans M, Kawachi S, Soriano A, Palacin A, Morise Z, Granger D, et al. Brain endothelial adhesion molecule expression in experimental colitis. Microcirculation 2001, 8: 105–114.CrossRefGoogle Scholar
  14. 14.
    Natah SS, Mouihate A, Pittman QJ, Sharkey KA. Disruption of the blood-brain barrier during TNBS colitis. Neurogastroenterol Motil 2005, 17: 433–446.CrossRefPubMedCentralGoogle Scholar
  15. 15.
    Frank DN, St Amand AL, Feldman RA, Boedeker EC, Harpaz N, Pace NR. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci U S A 2007, 104: 13780.CrossRefPubMedCentralGoogle Scholar
  16. 16.
    Jang SE, Lim SM, Jeong JJ, Jang HM, Lee HJ, Han MJ, et al. Gastrointestinal inflammation by gut microbiota disturbance induces memory impairment in mice. Mucosal Immunol 2017.Google Scholar
  17. 17.
    Caradonna L, Amati L, Magrone T, Pellegrino NM, Jirillo E, Caccavo D. Enteric bacteria, lipopolysaccharides and related cytokines in inflammatory bowel disease: biological and clinical significance. J Endotoxin Res 2000, 6: 205–214.PubMedGoogle Scholar
  18. 18.
    Yao YM, Xu CL, Yao FH, Yu Y, Sheng ZY. The pattern of nuclear factor-kappaB activation in rats with endotoxin shock and its role in biopterin-mediated nitric oxide induction. Zhonghua Shao Shang Za Zhi 2006, 22: 405–410.PubMedGoogle Scholar
  19. 19.
    Kremlev SG, Palmer C. Interleukin-10 inhibits endotoxin-induced pro-inflammatory cytokines in microglial cell cultures. J Neuroimmunol 2005, 162: 71–80.CrossRefPubMedCentralGoogle Scholar
  20. 20.
    Zhou Y, Huang X, Zhao T, Qiao M, Zhao X, Zhao M, et al. Hypoxia augments LPS-induced inflammation and triggers high altitude cerebral edema in mice. Brain Behav Immunity 2017, 64: 266–275.CrossRefGoogle Scholar
  21. 21.
    Sainathan SK, Bishnupuri KS, Aden K, Luo Q, Houchen CW, Anant S, et al. Toll-like receptor-7 ligand imiquimod induces type I interferon and antimicrobial peptides to ameliorate dextran sodium sulfate-induced acute colitis. Inflamm Bowel Dis 2012, 18: 955–967.CrossRefPubMedCentralGoogle Scholar
  22. 22.
    Håkansson Å1, Tormo-Badia N, Baridi A, Xu J, Molin G, Hagslätt ML, et al. Immunological alteration and changes of gut microbiota after dextran sulfate sodium (DSS) administration in mice. Clin Exp Med 2015, 15: 107–120.CrossRefPubMedCentralGoogle Scholar
  23. 23.
    Neilly MPJD, Gardiner KR, Kirk SJ, Jennings G, Anderson NH, Elia M, et al. Endotoxaemia and cytokine production in experimental colitis. Br J Surgery 1995, 82: 1479.CrossRefGoogle Scholar
  24. 24.
    Ghia JE, Blennerhassett P, Kumar-Ondiveeran H, Verdu EF, Collins SM. The vagus nerve: a tonic inhibitory influence associated with inflammatory bowel disease in a murine model. Gastroenterology 2006, 131: 1122–1130.CrossRefPubMedCentralGoogle Scholar
  25. 25.
    Dammann O, Leviton A. Maternal intrauterine infection, cytokines, and brain damage in the preterm newborn. Pediatr Res 1997, 42: 1.CrossRefPubMedCentralGoogle Scholar
  26. 26.
    Fang X, Sun D, Wang Z, Yu Z, Liu W, Pu Y, et al. MiR-30a positively regulates the inflammatory response of microglia in experimental autoimmune encephalomyelitis. Neurosci Bull 2017, 33: 603–615.CrossRefPubMedCentralGoogle Scholar
  27. 27.
    Buttini M, Limonta S, Boddeke HW. Peripheral administration of lipopolysaccharide induces activation of microglial cells in rat brain. Neurochem Int 1996, 29: 25.CrossRefPubMedCentralGoogle Scholar
  28. 28.
    Carson MJ. Microglia as liaisons between the immune and central nervous systems: Functional implications for multiple sclerosis. Glia 2002, 40: 218–231.CrossRefPubMedCentralGoogle Scholar
  29. 29.
    Alvarez JI, Cayrol R, Prat A. Disruption of central nervous system barriers in multiple sclerosis. Biochim Biophys Acta 2011, 1812: 252–264.CrossRefPubMedCentralGoogle Scholar
  30. 30.
    Krizanac-Bengez L, Kapural M, Parkinson F, Cucullo L, Hossain M, Mayberg MR, et al. Effects of transient loss of shear stress on blood-brain barrier endothelium: role of nitric oxide and IL-6. Brain Res 2003, 977: 239–246.CrossRefPubMedCentralGoogle Scholar
  31. 31.
    Blecharzlang KG, Wagner J, Fries A, Nieminenkelhä M, Rösner J, Schneider UC, et al. Interleukin 6-mediated endothelial barrier disturbances can be attenuated by blockade of the IL6 receptor expressed in brain microvascular endothelial cells. Transl Stroke Res 2018: 1–12.Google Scholar
  32. 32.
    Moreira AP, Texeira TF, Ferreira AB, Peluzio MC, Alfenas RC. Influence of a high-fat diet on gut microbiota, intestinal permeability and metabolic endotoxaemia. Br J Nutr 2012, 108: 801.CrossRefPubMedCentralGoogle Scholar
  33. 33.
    Lee IA, Bae EA, Hyun YJ, Kim DH. Dextran sulfate sodium and 2,4,6-trinitrobenzene sulfonic acid induce lipid peroxidation by the proliferation of intestinal gram-negative bacteria in mice. J Inflamm 2010, 7: 7.CrossRefGoogle Scholar
  34. 34.
    Ito H, Tanabe H, Kawagishi H, Tadashi W, Yasuhiko T, Sugiyama K, et al. Short-chain inulin-like fructans reduce endotoxin and bacterial translocations and attenuate development of TNBS-induced colitis in rats. Dig Dis Sci 2009, 54: 2100–2108.CrossRefPubMedCentralGoogle Scholar
  35. 35.
    Axelsson LG, Midtvedt T, Bylundfellenius AC. The role of intestinal bacteria, bacterial translocation and endotoxin in dextran sodium sulphate-induced colitis in the mouse. Microb Ecol Health Dis 1996, 9: 225–237.CrossRefGoogle Scholar

Copyright information

© Shanghai Institutes for Biological Sciences, CAS and Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Ying Han
    • 1
    • 2
  • Tong Zhao
    • 2
  • Xiang Cheng
    • 2
  • Ming Zhao
    • 2
  • Sheng-Hui Gong
    • 2
  • Yong-Qi Zhao
    • 2
  • Hai-Tao Wu
    • 2
  • Ming Fan
    • 1
    • 2
    • 3
    Email author
  • Ling-Ling Zhu
    • 2
    • 3
    Email author
  1. 1.Center for Brain Disorders Research, Capital Medical UniversityBeijing Institute of Brain DisordersBeijingChina
  2. 2.Institute of Military Cognition and Brain SciencesAcademy of Military Medical SciencesBeijingChina
  3. 3.Co-innovation Center of NeuroregenerationNantong UniversityNantongChina

Personalised recommendations