TRPV1 receptor-mediated expression of Toll-like receptors 2 and 4 following permanent middle cerebral artery occlusion in rats

Authors

  • Ali Roohbakhsh Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
  • Ali Shamsizadeh Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran|Department of Physiology and Pharmacology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  • Amir Moghadam-ahmadi Department of Neurology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  • Elham Hakimizadeh Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  • Gholamreza Bazmandegan Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran|Department of Physiology and Pharmacology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  • Hossein Rezazadeh Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  • Iman Fatemi Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran|Department of Physiology and Pharmacology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  • Mehdi Shariati Department of Anatomy, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  • Mohammad Allahtavakoli Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran|Department of Physiology and Pharmacology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  • Mohammad Kazemi Arababadi Department of Laboratory Sciences, School of Paramedicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  • Mohammad Reza Hajizadeh Molecular Medicine Research Center, Department of Biochemistry, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
Abstract:

Objective(s): Stroke is known as a main cause of mortality and prolonged disability in adults. Both transient receptor potential V1 (TRPV1) channels and toll-like receptors (TLRs) are involved in mediating the inflammatory responses. In the present study, the effects of TRPV1 receptor activation and blockade on stroke outcome and gene expression of TLR2 and TLR4 were assessed following permanent middle cerebral artery occlusion in rats Materials and Methods: Eighty male Wistar rats were divided into four groups as follows: sham, vehicle, AMG9810 (TRPV1 antagonist) -treated and capsaicin (TRPV1 agonist) -treated. For Stroke induction, the middle cerebral artery was permanently occluded and then behavioral functions were evaluated 1, 3 and 7 days after stroke. Results: TRPV1 antagonism significantly reduced the infarct volume compared to the stroke group. Also, neurological deficits were decreased by AMG9810 seven days after cerebral ischemia. In the ledged beam-walking test, the slip ratio was enhanced following ischemia. AMG9810 decreased this index in stroke animals. However, capsaicin improved the ratio 3 and 7 days after cerebral ischemia. Compared to the sham group, the mRNA expression of TLR2 and TLR4 was significantly increased in the stroke rats. AMG9810 Administration significantly reduced the mRNA expression of TLR2 and TLR4. However, capsaicin did not significantly affect the gene expression of TLR2 and TLR4. Conclusion: Our results demonstrated that TRPV1 antagonism by AMG9810 attenuates behavioral function and mRNA expression of TLR2 and TLR4. Thus, it might be useful to shed light on future therapeutic strategies for the treatment of ischemic stroke.

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Journal title

volume 20  issue 8

pages  863- 869

publication date 2017-08-01

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