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Inhibition of transient receptor potential vanilloid‐1 confers neuroprotection, reduces tumor necrosis factor‐alpha, and increases IL‐10 in a rat stroke model
Author(s) -
Hakimizadeh Elham,
Shamsizadeh Ali,
Roohbakhsh Ali,
Arababadi Mohammad Kazemi,
Hajizadeh Mohammad R.,
Shariati Mehdi,
Rahmani Mohammad R.,
Allahtavakoli Mohammad
Publication year - 2017
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/fcp.12279
Subject(s) - trpv , medicine , stroke (engine) , neuroprotection , agonist , capsaicin , tumor necrosis factor alpha , antagonist , trpv1 , anesthesia , receptor , transient receptor potential channel , endocrinology , pharmacology , mechanical engineering , engineering
Stroke is a major cause of mortality and long‐term disability in adults. Transient receptor potential vanilloid‐1 ( TRPV 1) plays a crucial role in neuroinflammation. In this study, the effects of TRPV 1 agonist (capsaicin) and antagonist ( AMG 9810) on cerebral ischemia were investigated. Forty male Wistar rats were assigned to the following experimental groups: sham, vehicle) ischemic), AMG 9810 (selective TRPV 1 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 TRPV 1, and serum concentrations of tumor necrosis factor‐alpha ( TNF ‐α) and IL ‐10 were measured. Compared to the vehicle group, AMG 9810 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 AMG 9810 ( P < 0.01 and P < 0.001 vs. vehicle) 3 and 7 days after stroke. Compared to the sham group, the mRNA expression of TRPV 1 was significantly increased in vehicle group ( P < 0.01). Administration of AMG 9810 significantly increased the anti‐inflammatory cytokine IL ‐10 and decreased the inflammatory cytokine TNF ‐α ( P < 0.05). Moreover, our results indicate that AMG 9810 might a promising candidate for the hypothermic treatment of stroke. The findings also suggest a key role for AMG 9810 in reducing inflammation after stroke and imply that TRPV 1 could be a potential target for the treatment of ischemic stroke.