Neuroprotective Effect of TRPA1 Activation in Focal Cerebral Ischemia: Insights from Wild-Type and Knockout Mice

Title

Abstract

Hypothermia and focal brain cooling (FBC) demonstrate neuroprotective effects in ischemic stroke, but their invasiveness limits clinical use. We explored transient receptor potential (TRP) channels as an alternative, focusing on TRP Ankyrin 1 (TRPA1), which operates within the temperature range of FBC. Activation of TRPA1 has been reported to offer neuroprotection, suggesting it may contribute to the effects seen with FBC. We hypothesized that pharmacological activation of TRPA1 could replicate the neuroprotective effects of FBC, providing a less invasive treatment for cerebral infarction. We examined the effects of a TRPA1 agonist and FBC in focal cerebral ischemia induced by photochemically triggered thrombosis in wild-type (WT) and TRPA1 knockout (KO) mice. In WT mice, intracerebroventricular administration of the TRPA1 agonist allyl isothiocyanate reduced infarct size by approximately half, comparable to FBC. TRPA1 KO mice had larger infarcts than WT, but FBC significantly reduced infarct size in both groups. Furthermore, Evans blue extravasation, used to assess the extent of blood-brain barrier disruption, was approximately twice as high in TRPA1KO mice compared to WT mice. These findings underscore the neuroprotective potential of TRPA1 agonists and the increased vulnerability against ischemia with TRPA1 deficiency. However, the neuroprotective effects of TRPA1 activation are likely mediated by a mechanism distinct from that of FBC. Our study suggests TRPA1 channels are crucial for ischemic stroke protection and may offer a novel therapeutic approach.

Creators Okazaki Koki

Creators Oka Fumiaki