A pathophysiological role of TRPV1 in ischemic injury after transient focal cerebral ischemia in mice

• Miyanohara, Jun

  Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University

• Shirakawa, Hisashi

  Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University

• Sanpei, Kazuaki

  Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University

• Nakagawa, Takayuki

  Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University･Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital

• Kaneko, Shuji

  Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University

Abstract

Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel with high Ca²⁺ permeability, which functions as a polymodal nociceptor activated by heat, protons and several vanilloids, including capsaicin and anandamide. Although TRPV1 channels are widely distributed in the mammalian brain, their pathophysiological roles in the brain remain to be elucidated. In this study, we investigated whether TRPV1 is involved in cerebral ischemic injury using a middle cerebral artery (MCA) occlusion model in wild-type (WT) and TRPV1-knockout (KO) mice. For transient ischemia, the left MCA of C57BL/6 mice was occluded for 60 min and reperfused at 1 and 2 days after ischemia. We found that neurological and motor deficits, and infarct volumes in TRPV1-KO mice were lower than those of WT mice. Consistent with these results, intracerebroventricular injection of a TRPV1 antagonist, capsazepine (20 nmol), 30 min before the onset of ischemia attenuated neurological and motor deficits and improved infarct size without influencing cerebral blood flow in the occluded MCA territory. The protective effect of capsazepine on ischemic brain damage was not observed in TRPV1-KO mice. WT and TRPV1-KO mice did not show any differences with respect to the increased number of Iba1-positive microglia/macrophages, GFAP-positive astrocytes, and Gr1-positive neutrophils at 1 and 2 days after cerebral ischemia. Taken together, we conclude that brain TRPV1 channels are activated by ischemic stroke and cause neurological and motor deficits and infarction after brain ischemia.

Journal

• Biochemical and Biophysical Research Communications

  Biochemical and Biophysical Research Communications 467 (3), 478-483, 2015-11-20

  Elsevier BV

Keywords

• TRPV1
• Knockout mouse
• Middle cerebral artery occlusion
• Ischemic injury
• Capsazepine

Details

• CRID: 1050845763236857984
• NII Article ID: 120006630996
• NII Book ID: AA00564395
• ISSN: 0006291X
• HANDLE: 2433/241624
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • CiNii Articles