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.