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A Novel Animal Model of Dysphagia Following Stroke

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Abstract

Patients who have an ischemic stroke are at high risk of swallowing disorders. Aspiration due to swallowing disorders, specifically delayed trigger of the pharyngeal stage of swallowing, predisposes such patients to pneumonia. In the present study, we evaluated swallowing reflex in a rat model of transient middle cerebral artery occlusion (tMCAO), which is one of the most common experimental animal models of cerebral ischemia, in order to develop a novel animal model of dysphagia following ischemic stroke. A swallowing reflex was elicited by a 10-s infusion of distilled water (DW) to the pharyngolaryngeal region in the tMCAO rat model. Swallowing reflex was estimated using the electromyographic activity of the mylohyoid muscle from 1 to 3 weeks after surgery. Two weeks after tMCAO, the number of swallows significantly decreased and the onset latency of the first swallow was prolonged compared with that of the sham group. The number of swallows in rats significantly increased by infusions of 10 mM citric acid and 0.6 μM capsaicin to the pharyngolaryngeal region compared with the number from infusion of DW. It has been reported that sensory stimulation of the pharyngolaryngeal region with citric acid, capsaicin, and l-menthol ameliorates hypofunction of pharyngeal-stage swallowing in dysphagia patients. Therefore, the tMCAO rat model may show some of the symptoms of pharyngeal-stage swallowing disorders, similar to those in patients with ischemic stroke. This rat tMCAO model has the potential to become a novel animal model of dysphagia following stroke that is useful for development of therapeutic methods and drugs.

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References

  1. Gordon C, Hewer RL, Wade DT. Dysphagia in acute stroke. Br Med J (Clin Res Ed). 1987;295(6595):411–4.

    Article  CAS  Google Scholar 

  2. Ding R, Logemann JA. Pneumonia in stroke patients: a retrospective study. Dysphagia. 2000;15(2):51–7.

    CAS  PubMed  Google Scholar 

  3. Heuschmann PU, Kolominisky-Raba PL, Misselwitz B, Hermanek P, Leffmann C, Janzen RW, Rother J, Buecker-Nott HJ, Berger K. Predictors of in-hospital mortality and attributable risks of death after ischemic stroke. The German stroke registers study group. Arch Intern Med. 2004;164:1761–8.

    Article  PubMed  Google Scholar 

  4. Hinchey JA, Shephard T, Furie K, Smith D, Wang D, Tonn S. Formal dysphagia screening protocols prevent pneumonia. Stroke. 2005;36:1972–6.

    Article  PubMed  Google Scholar 

  5. Kimura K, Minematsu K, Kazui S, Yamaguchi T. Mortality and cause of death after hospital discharge in 10,981 patients with ischemic stroke and transient ischemic attack. Cerebrovasc Dis. 2005;19:171–8.

    Article  PubMed  Google Scholar 

  6. Palmer JB, Drennan JC, Baba M. Evaluation and treatment of swallowing impairments. Am Fam Physician. 2000;61(8):2453–62.

    CAS  PubMed  Google Scholar 

  7. Logemann JA. Dysphagia: evaluation and treatment. Folia Phoniatr Logop. 1995;47(3):140–64.

    Article  CAS  PubMed  Google Scholar 

  8. Smithard DG, O’Neill PA, England RE, Park CL, Wyatt R, Martin DF, Morris J. The natural history of dysphagia following a stroke. Dysphagia. 1997;12(4):188–93.

    Article  CAS  PubMed  Google Scholar 

  9. Lawrence ES, Coshall C, Dundas R, Stewart J, Rudd AG, Howard R, Wolfe CD. Estimates of the prevalence of acute stroke impairments and disability in a multiethnic population. Stroke. 2001;32(6):1279–84.

    Article  CAS  PubMed  Google Scholar 

  10. Paciaroni M, Mazzotta G, Corea F, Caso V, Venti M, Milia P, Silvestrelli G, Palmerini F, Parnetti L, Gallai V. Dysphagia following stroke. Eur Neurol. 2004;51(3):162–7.

    Article  PubMed  Google Scholar 

  11. Robbins J, Levine RL, Maser A, Rosenbek JC, Kempster GB. Swallowing after unilateral stroke of the cerebral cortex. Arch Phys Med Rehabil. 1993;74(12):1295–300.

    Article  CAS  PubMed  Google Scholar 

  12. Hossmann KA. Experimental models for the investigation of brain ischemia. Cardiovasc Res. 1998;39(1):106–20.

    Article  CAS  PubMed  Google Scholar 

  13. Zhang N, Miyamoto N, Tanaka R, Mochizuki H, Hattori N, Urabe T. Activation of tyrosine hydroxylase prevents pneumonia in a rat chronic cerebral hypoperfusion model. Neuroscience. 2009;158(2):665–72.

    Article  CAS  PubMed  Google Scholar 

  14. Liu F, McCullough LD. Middle cerebral artery occlusion model in rodents: methods and potential pitfalls. J Biomed Biotechnol. 2011;2011:464701.

    PubMed Central  PubMed  Google Scholar 

  15. Bederson JB, Pitts LH, Tsuji M, Nishimura MC, Davis RL, Bartkowski H. Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination. Stroke. 1986;17(3):472–6.

    Article  CAS  PubMed  Google Scholar 

  16. Belayev L, Alonso OF, Busto R, Zhao W, Ginsberg MD. Middle cerebral artery occlusion in the rat by intraluminal suture. Neurological and pathological evaluation of an improved model. Stroke. 1996;27(9):1616–22.

    Article  CAS  PubMed  Google Scholar 

  17. Logemann JA, Pauloski BR, Colangelo L, Lazarus C, Fujiu M, Kahrilas PJ. Effects of a sour bolus on oropharyngeal swallowing measures in patients with neurogenic dysphagia. J Speech Hear Res. 1995;38(3):556–63.

    CAS  PubMed  Google Scholar 

  18. Ebihara S, Kohzuki M, Sumi Y, Ebihara T. Sensory stimulation to improve swallowing reflex and prevent aspiration pneumonia in the elderly dysphagic people. J Pharmacol Sci. 2011;115(2):99–104.

    Article  CAS  PubMed  Google Scholar 

  19. Koizumi J, Yoshida Y, Nakazawa T, Ooneda G. Experimental studies of ischemic brain edema. 1. A new experimental model of cerebral embolism in rats in which recirculation can be introduced in the ischemic area. Jpn J Stroke. 1986;8:1–8.

    Article  Google Scholar 

  20. Kitagawa J, Nakagawa K, Hasegawa M, Iwakami T, Shingai T, Yamada Y, Iwata K. Facilitation of reflex swallowing from the pharynx and larynx. J Oral Sci. 2009;51(2):167–71.

    Article  PubMed  Google Scholar 

  21. Doty RW. Neural organization of deglutition. In: Code CF, editor. Handbook of physiology. Washington, D.C.: American Physiology Society; 1968. p. 1861–902.

    Google Scholar 

  22. Kajii Y, Shingai T, Kitagawa J, Takahashi Y, Taguchi Y, Noda T, Yamada Y. Sour taste stimulation facilitates reflex swallowing from the pharynx and larynx in the rat. Physiol Behav. 2002;77(2–3):321–5.

    Article  CAS  PubMed  Google Scholar 

  23. Cliff MA, Green BG. Sensitization and desensitization to capsaicin and menthol in the oral cavity: interactions and individual differences. Physiol Behav. 1996;59(3):487–94.

    Article  CAS  PubMed  Google Scholar 

  24. Jean A. Brain stem control of swallowing: neuronal network and cellular mechanisms. Physiol Rev. 2001;81(2):929–69.

    CAS  PubMed  Google Scholar 

  25. Jean A. Brainstem control of swallowing: localization and organization of the central pattern generator for swallowing. In: Taylor A, editor. Neurophysiology of the Jaws and Teeth. London: MacMillan; 1990. p. 294–321.

    Google Scholar 

  26. Miller AJ. Deglutition. Physiol Rev. 1982;62(1):129–84.

    CAS  PubMed  Google Scholar 

  27. Martin RE, Sessle BJ. The role of the cerebral cortex in swallowing. Dysphagia. 1993;8(3):195–202.

    Article  CAS  PubMed  Google Scholar 

  28. Nagasawa H, Kogure K. Exo-focal postischemic neuronal death in the rat brain. Brain Res. 1990;524(2):196–202.

    Article  CAS  PubMed  Google Scholar 

  29. Du C, Hu R, Csernansky CA, Hsu CY, Choi DW. Very delayed infarction after mild focal cerebral ischemia: a role for apoptosis? J Cereb Blood Flow Metab. 1996;16(2):195–201.

    Article  CAS  PubMed  Google Scholar 

  30. Robbins J, Levin RL. Swallowing after unilateral stroke of the cerebral cortex: preliminary experience. Dysphagia. 1988;3(1):11–7.

    Article  CAS  PubMed  Google Scholar 

  31. Daniels SK, Foundas AL, Iglesia GC, Sullivan MA. Lesion site in unilateral stroke patients with dysphagia. J Stroke Cerebrovasc Dis. 1996;6(1):30–4.

    Article  CAS  PubMed  Google Scholar 

  32. Irie H, Lu CC. Dynamic evaluation of swallowing in patients with cerebrovascular accident. Clin Imaging. 1995;19(4):240–3.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors thank Dr. T. Kobayashi for animal surgery, Dr. T. Shingai for measurement of swallowing, Dr. S. Katsumata, and Dr. T. Umekawa for commenting on the manuscript, and S. Orimoto for English proofreading.

Conflict of interest

The authors have no conflicts of interest to disclose.

Author information

Authors and Affiliations

  1. Food Technology Section, Industrial Research Institute of Shizuoka Prefecture, 2078 Makigaya, Aoi-ku, Shizuoka-shi, Shizuoka, 421-1298, Japan

    Naoto Sugiyama

  2. Project Management, Translational Medicine Center, Ono Pharmaceutical Co., Ltd., 3-1-1 Sakurai, Shimamoto-cho, Mishima-gun, Osaka, 618-8585, Japan

    Eiji Nishiyama

  3. Discovery Research Laboratories I, Minase Research Institute, Ono Pharmaceutical Co., Ltd., 3-1-1 Sakurai, Shimamoto-cho, Mishima-gun, Osaka, 618-8585, Japan

    Yukitoshi Nishikawa, Takashi Sasamura & Shinji Nakade

  4. Planning Department, Industrial Research Institute of Shizuoka Prefecture, 2078 Makigaya, Aoi-ku, Shizuoka-shi, Shizuoka, 421-1298, Japan

    Katsumasa Okawa

  5. Electronic Technology Section, Industrial Research Institute of Shizuoka Prefecture, 2078 Makigaya, Aoi-ku, Shizuoka-shi, Shizuoka, 421-1298, Japan

    Tadashi Nagasawa

  6. Environment Technology Section, Industrial Research Institute of Shizuoka Prefecture, 2078 Makigaya, Aoi-ku, Shizuoka-shi, Shizuoka, 421-1298, Japan

    Akane Yuki

Authors
  1. Naoto Sugiyama
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  2. Eiji Nishiyama
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  3. Yukitoshi Nishikawa
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  4. Takashi Sasamura
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  5. Shinji Nakade
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  6. Katsumasa Okawa
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  7. Tadashi Nagasawa
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  8. Akane Yuki
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Corresponding author

Correspondence to Naoto Sugiyama.

Additional information

N. Sugiyama and E. Nishiyama have contributed equally to this study.

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Sugiyama, N., Nishiyama, E., Nishikawa, Y. et al. A Novel Animal Model of Dysphagia Following Stroke. Dysphagia 29, 61–67 (2014). https://doi.org/10.1007/s00455-013-9481-x

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  • DOI: https://doi.org/10.1007/s00455-013-9481-x

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