TRPV۱ receptor-mediated expression of Toll-like receptors ۲ and ۴ following permanent middle cerebral artery occlusion in rats

Objective(s): Stroke is known as a main cause of mortality and prolonged disability in adults. Both transient receptor potential V۱ (TRPV۱) channels and toll-like receptors (TLRs) are involved in mediating the inflammatory responses. In the present study, the effects of TRPV۱ receptor activation and blockade on stroke outcome and gene expression of TLR۲ and TLR۴ were assessed following permanent middle cerebral artery occlusion in rats Materials and Methods: Eighty male Wistar rats were divided into four groups as follows: sham, vehicle, AMG۹۸۱۰ (TRPV۱ antagonist) -treated and capsaicin (TRPV۱ agonist) -treated. For Stroke induction, the middle cerebral artery was permanently occluded and then behavioral functions were evaluated ۱, ۳ and ۷ days after stroke. Results: TRPV۱ antagonism significantly reduced the infarct volume compared to the stroke group. Also, neurological deficits were decreased by AMG۹۸۱۰ seven days after cerebral ischemia. In the ledged beam-walking test, the slip ratio was enhanced following ischemia. AMG۹۸۱۰ decreased this index in stroke animals. However, capsaicin improved the ratio ۳ and ۷ days after cerebral ischemia. Compared to the sham group, the mRNA expression of TLR۲ and TLR۴ was significantly increased in the stroke rats. AMG۹۸۱۰ Administration significantly reduced the mRNA expression of TLR۲ and TLR۴. However, capsaicin did not significantly affect the gene expression of TLR۲ and TLR۴. Conclusion: Our results demonstrated that TRPV۱ antagonism by AMG۹۸۱۰ attenuates behavioral function and mRNA expression of TLR۲ and TLR۴. Thus, it might be useful to shed light on future therapeutic strategies for the treatment of ischemic stroke.

Keywords:

Cerebral ischemia , Inflammation , TLR۴ , TLR۲ , TRPV۱