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

Abstract

Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel with high Ca(2+) 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.

• Authors: Jun Miyanohara, Hisashi Shirakawa, Kazuaki Sanpei, Takayuki Nakagawa, Shuji Kaneko
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 467 Issue 3 Pg. 478-83 (Nov 20 2015) ISSN: 1090-2104 [Electronic] United States
• PMID: 26456642 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• TRPV Cation Channels
• TRPV1 protein, mouse
• capsazepine
• Capsaicin

Topics

• Animals
• Brain Ischemia (physiopathology, prevention & control)
• Capsaicin (analogs & derivatives, pharmacology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• TRPV Cation Channels (genetics, physiology)