Vestibular Stimulation as An Interventional Approach for Cold Water Stress Induced Immunological and Histopathological Changes in Rats

DOI: 10.18805/IJAR.B-4491    | Article Id: B-4491 | Page : 830-836
Citation :- Vestibular Stimulation as An Interventional Approach for Cold Water Stress Induced Immunological and Histopathological Changes in Rats.Indian Journal of Animal Research.2022.(56):830-836
T. Rama Kranthi, R. Archana, S. Senthilkumar ramakranthy@gmail.com
Address : Department of Physiology, Prathima Institute of Medical Sciences, Karimnagar-505 529, Telangana, India.
Submitted Date : 19-04-2021
Accepted Date : 7-07-2021


Background: Chronic exposure to stress results in immuno-suppression. The present study was carried out to explore the therapeutic benefits of vestibular stimulation on the immune system of stress-induced Wistar rats. 
Methods: Stress was intervened in the Wistar rats by cold water swimming method for a period of 14 days. Following stress, caloric vestibular stimulation was induced in the rats by irrigating external auditory meatus bilaterally with hot water (temperature 41oC) for 2 minutes for a period of 15 days and 30 days in respective groups. At the end of the experiment, blood samples were obtained and serum corticosterone, Interleukin 2 (IL2), Immunoglobulin M (IgM) levels were analyzed using ELISA method and histopathology of brain was assessed. Brain CD4 and CD8 cells were analyzed by Immunohistochemistry. 
Result: Stress significantly increased serum corticosterone, IL2 levels and reduced IgM levels. Stress group showed increased dendritic arborization in prefrontal cortex, neuronal atrophy, nuclear pyknosis with congested blood vessels in hippocampus and mononuclear cell inflammatory infiltrate in hypothalamus. Brain extravascular CD4 and CD8 showed positive in stress group. Caloric vestibular stimulation effectively reduced serum corticosterone levels, histopathological changes, brain extravascular CD4 and CD8 cells and improved IgM in the present study.


Caloric vestibular stimulation Cold water swimming stress CD4 CD8 Histopathology IgM IL2 Stress


  1. Atanackovic, D., Schnee, B., Schuch. G., Faltz, C., Schulze, J., Weber, C.S., Schafhausen, P., Bartels, K., Bokemeyer, C., Brunner-Weinzierl, Mc. and Deter, H C. (2006). Acute psychological stress alerts the adaptive immune response: Stress-induced mobilization of effector T cells. Journal of Neuroimmunology. 176(1-2): 141-152. 
  2. Batuman, O.A., Sajewski, D., Ottenweller, J.E., Pitman, D. and Natelson, B.H. (1990). Effects of repeated stress on T cell numbers and function in rats. Brain, Behavior and Immunity. 4(2): 105-117. 
  3. Brandt, T., Schautzer, F., Hamilton, D. A., Brüning, R., Markowitsch, H.J., Kalla, R., Darlington, C., Smith, P. and Strupp, M. (2005). Vestibular loss causes hippocampal atrophy and impaired spatial memory in humans. Brain. 128(11): 2732-2741.
  4. Devi, N.P. and Mukkadan, J.K. (2017). Impact of Rotatory Vestibular Stimulation in Memory Boosting. MOJ Anat. and Physiol. 4(4): 00143.
  5. Ehrenstein, M.R. and Notley, C. A. (2010). The importance of natural IgM: Scavenger, protector and regulator. Nature Reviews Immunology. 10(11): 778-786.
  6. Felten, S.Y. and Felten, D l. (1994). Neural-immune interactions. Prog Brain Res. 100: 157-162. 
  7. Himmerich, H., Fischer, J., Bauer, K., Kirkby, K.C., Sack, U. and Krügel, U. (2013). Stress-induced cytokine changes in rats. European Cytokine Network. 24(2): 97-103. 
  8. Jinu, K., Mukkadan, J. and Archana, R. (2018). Effect of bilateral and unilateral caloric vestibular stimulation in scopolamine induced dementia in Wistar albino rats. Biomedical Research. 29(15). 
  9. Joëls, M., Karst, H., Alfarez, D., Heine, Vm., Qin, Y., Van Riel, E., Verkuyl, M., Lucassen, Pj and Krugers, Hj. (2004). Effects of chronic stress on structure and cell function in rat hippocampus and hypothalamus. Stress. 7(4): 221-231. 
  10. Khan, A. R., Geiger, L., Wiborg, O. and Czéh, B. (2020). Stress- Induced Morphological, Cellular and Molecular Changes in the Brain-Lessons Learned from the Chronic Mild Stress Model of Depression. Cells. 9(4), 1026. 
  11. Kumar, S.S., Usha, R., Padnabha, J. A. and Mukkadan, J.K. (2014). Can Controlled Vestibular Stimulation Delay Brain Aging? Asian Journal of Health Sciences. 2(1). 
  12. Lee, S., Kang, B.M., Kim, J.H., Min, J., Kim, H.S., Ryu, H., Park, H., Bae, S., Oh, D., Choi, M. and Suh, M.  (2018).  Real-time in vivo two- photon imaging study reveals decreased cerebro-vascular volume and increased blood-brain barrier permeability in chronically stressed mice. Scientific Reports. 8(1): 1-14.
  13. Liao, W., Lin, J.X., and Leonard, W.J. (2013). Interleukin-2 at the crossroads of effector responses, tolerance and immunotherapy. Immunity. 38(1): 13-25. 
  14. Makwana, C.R.S., Shreesha, P., Urvesh, P, Harshad, M., Chirag, F., Dhaval. (2019). Status of oxidative stress in cerebral cortex and testes, acetylcholinesterase activity in cerebral cortex and sperm parameters in cadmium-exposed rats. Indian Journal of Animal Research. B-3844. 1-9. 
  15. Malek, T.R. (2003). The main function of IL-2 is to promote the development of T regulatory cells. J. Leukoc. Biol., Dec, 74(6): 961-965.
  16. Mcewen, B.S. and Gianaros, P.J. (2010). Central role of the brain in stress and adaptation: links to socioeconomic status, health and disease. Ann. N Y Acad. Sci. 1186: 190-222  
  17. Miller, S.M. and  Ngo T.T. (2007). Studies of caloric vestibular stimulation: implications for the cognitive neurosciences, the clinical neurosciences and neurophilosophy. Acta Neuropsychiatrica. 19(3): 183-203. 
  18. Moazzam, S., Hussain, M.M. and Ahmad, T.A. (2013). Effect of chronic restraint stress on immune status of male Sprague Dawley rats. J. Coll. Physicians Surg. Pak. 23(7): 487-490. 
  19. Morawski, P.A., Qi, C.F. and  Bolland, S. (2017). Non-pathogenic tissue-resident CD8+ T cells uniquely accumulate in the brains of lupus-prone mice. Scientific Reports. 7(1) : 1-13. 
  20. Nagaraja, H. and Jeganathan, P.S. (1999). Forced swimming stress- induced changes in the physiological and biochemical parameters in albino rats. Indian Journal of Physiology and Pharmacology. 43:  53-59.
  21. Padgett, D.A. and Glaser, R. (2003). How stress influences the immune response. Trends in Immunology. 24(8): 444-448.
  22. Rajagopalan, A., Goothy, S.S., Johny, M. and Mukkadan, J.K. (2017). Modulation of immune responses in stress by vestibular stimulation. National Journal of Physiology, Pharmacy and Pharmacology. 7(11): 1, January. 
  23. Ravikumar, Y., Madhuri, D., Lakshman, M., Reddy, A.G. and Kalakumar, B. (2021). Changes in Biochemical Parameters, Antioxidative Enzymes and Histopathology of Liver Induced by Cadmium (Cd) and Chlorpyrifos (CPF) in Wistar Rats. Indian Journal of Animal Research. 10. B-4178: 1-5.
  24. Sailesh, K.S. and Mukkadan, J. (2013). Can controlled vestibular stimulation reduce stress. Health Sciences.  2(3): 1-13. 
  25. Sangeeta, B., Zheng, Y. and Smith, P.F. (2016). Basal dendritic length is reduced in the rat hippocampus following bilateral vestibular deafferentation. Neurobiology of Learning and Memory. 131: 56-60. 
  26. Sapolsky, R.M., Romero, L.M., and Munck, A.U. (2000). How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions. Endocrine Reviews. 21(1): 55-89. 
  27. Schneiderman, N., Ironson, G. and Siegel, S.D. (2005). Stress and health: psychological, behavioral and biological determinants. Annu. Rev. Clin. Psychol. 1: 607-628.  
  28. Sheridan, J.F., Feng, N.G., Bonneau, R.H., Allen, C.M., Huneycutt, B.S. and Glaser, R. (1991). Restraint stress differentially affects anti-viral cellular and humoral immune responses in mice. Journal of Neuroimmunology. 31(3): 245-255. 
  29. Smith, P.F., Geddes, L.H., Baek, J.H., Darlington, C.L. and Zheng, Y. (2010). Modulation of memory by vestibular lesions and galvanic vestibular stimulation. Front Neurol. 1:14, 1.
  30. Stackman, R.W. and Herbert, A. M. (2002). Rats with lesions of the vestibular system require a visual landmark for spatial navigation. Behav. Brain Res. 128(1): 27-40. 
  31. Varghese, V., Kumar, S. S., Archana, R. and Mukkadan, J.K. (2015). Vestibular modulation of thyroid function in forced cold water swimming stress induced Wistar albino rats. Int. J. Res. Ayurveda Pharm. 6: 513-515. 
  32. White-Traut, Rc, Schwertz, D., Mcfarlin, B. and Kogan, J. (2009). Salivary cortisol and behavioral state responses of healthy newborn infants to tactile-only and multisensory interventions. J. Obstet. Gynecol. Neonatal. Nurs. 38(1): 22-34. 
  33. Wilkinson, D., Morris, R., Milberg, W. and Sakel, M. (2013) Caloric vestibular stimulation in aphasic syndrome. Frontiers in Integrative Neuroscience. 7: 99. 
  34. Xu, G., Li, Y., Ma, C., Wang, C., Sun, Z., Shen, Y., Liu, L., Li, S., Zhang, X. and Cong, B. (2019). Restraint stress induced hyperpermeability and damage of the blood-brain barrier in the amygdala of adult rats. Frontiers in Molecular Neuroscience. 12: 32. 
  35. Zettl, A., Rüdiger, T., Konrad, M.A. and Chott, A. (2004). Genomic profiling of peripheral T-cell lymphoma, unspecified, and anaplastic large T-cell lymphoma delineates novel recurrent chromosomal alterations. The American Journal of Pathology. 164(5): 1837-1848. 
  36. Zheng, Y., Balabhadrapatruni, S., Baek, J.H., Chung, P., Gliddon, C., Zhang, M., Darlington, C. L, Napper, R., Strupp, M., Brandt, T. and Smith, P.F. (2012). The Effects of Bilateral Vestibular Loss on Hippocampal 141 Volume, Neuronal Number and Cell Proliferation in Rats. Front Neurol. 3(20).

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