title: Inhibition of transient receptor potential vanilloid-1 confers neuroprotection, reduces tumor necrosis factor-alpha, and increases IL-10 in a rat stroke model.
abstract: Stroke is a major cause of mortality and long-term disability in adults. Transient receptor potential vanilloid-1 (TRPV1) plays a crucial role in neuroinflammation. In this study, the effects of TRPV1 agonist (capsaicin) and antagonist (AMG9810) on cerebral ischemia were investigated. Forty male Wistar rats were assigned to the following experimental groups: sham, vehicle) ischemic), AMG9810 (selective TRPV1 antagonist, 0.5 mg/kg; 3 h after stroke), and capsaicin (1 mg/kg; 3 h after stroke). Stroke was induced by permanent middle cerebral artery occlusion and neurological deficits were evaluated 1, 3, and 7 days after stroke. Then, infarct volume, brain edema, body temperature, mRNA expression of TRPV1, and serum concentrations of tumor necrosis factor-alpha (TNF-α) and IL-10 were measured. Compared to the vehicle group, AMG9810 significantly decreased the infarct volume (P < 0.01). Latency for the removal of sticky labels from the forepaw and the hanging time were significantly decreased and increased, respectively, following administration of AMG9810 (P < 0.01 and P < 0.001 vs. vehicle) 3 and 7 days after stroke. Compared to the sham group, the mRNA expression of TRPV1 was significantly increased in vehicle group (P < 0.01). Administration of AMG9810 significantly increased the anti-inflammatory cytokine IL-10 and decreased the inflammatory cytokine TNF-α (P < 0.05). Moreover, our results indicate that AMG9810 might a promising candidate for the hypothermic treatment of stroke. The findings also suggest a key role for AMG9810 in reducing inflammation after stroke and imply that TRPV1 could be a potential target for the treatment of ischemic stroke.
authors.affiliation: Physiology-Pharmacology Research Center, Emam Ali Boulevard, Rafsanjan University of Medical Sciences, Rafsanjan, 7717933777, Iran.
authors.forename: Elham
authors.initials: E
authors.lastname: Hakimizadeh
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Emam Ali Boulevard, Rafsanjan University of Medical Sciences, Rafsanjan, 7717933777, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Shamsizadeh
authors.affiliation: Pharmaceutical Research Center, University street, Mashhad University of Medical Sciences, Mashhad, 1394491388, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Roohbakhsh
authors.affiliation: Department of Laboratory Sciences, Faculty of Paramedicine, Emam Ali Boulevard, Rafsanjan University of Medical Sciences, Rafsanjan, 7717933777, Iran.
authors.forename: Mohammad Kazemi
authors.initials: MK
authors.lastname: Arababadi
authors.affiliation: Department of Biochemistry, Molecular Medicine Research Center, Emam Ali Boulevard, Rafsanjan University of Medical Sciences, Rafsanjan, 7717933777, Iran.
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Hajizadeh
authors.affiliation: Department of Anatomy, School of Medicine, Emam Ali Boulevard, Rafsanjan University of Medical Sciences, Rafsanjan, 7717933777, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Shariati
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Emam Ali Boulevard, Rafsanjan University of Medical Sciences, Rafsanjan, 7717933777, Iran.
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Rahmani
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Emam Ali Boulevard, Rafsanjan University of Medical Sciences, Rafsanjan, 7717933777, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Allahtavakoli
mesh_terms: D000178:Acrylamides / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D016753:Interleukin-10 / Q000097:blood*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000097:blood* / Q000188:drug therapy; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000097:blood*
chemical_list: C500530:3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo(b)(1,4)dioxin-6-yl)acrylamide; D000178:Acrylamides; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018696:Neuroprotective Agents; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10
keywords: IL-10; cerebral ischemia; neuroprotection; transient receptor potential vanilloid-1; tumor necrosis factor-alpha