Intranasal Salvinorin A Improves Long-term Neurological Function via Immunomodulation in a Mouse Ischemic Stroke Model

In this study, adult male mice were subjected to transient Middle Cerebral Artery Occlusion (tMCAO) and then were treated intranasally with SA (50  μg/kg) or with the vehicle dimethyl sulfoxide (DMSO). Multiple behavioral tests were used to evaluate neurofunction. Flow cytometry and immunofluorescence staining were used to evaluate the infiltration of peripheral immune cells into the brain. The tracer cadaverine and endogenous immunoglobuli n G (IgG) extravasation were used to detect blood brain barrier leakage. We observed that SA intranasal administration after ischemic stroke decreased the expression of pro-inflammatory factors in the brain. SA promoted the polarization of microglia/macrophages into a transitional phenotype and decr eased the pro-inflammatory phenotype in the brain after tMCAO. Interestingly, SA treatment scarcely altered the number of peripheral immune cells but decreased the macrophage and neutrophil infiltration into the brain at 24 h after tMCAO. Furthermore, SA treatment also preserved BBB integrity, redu ced long-term brain atrophy and white matter injury, as well as improved the long-term neurofunctional outcome in mice. In this study, intranasal administration of SA improved long-term neurological function via immuno-modulation and by preserving blood–brain barrier integrity in a mouse ischemic stroke model, suggesting that SA could potentially serve as an alternative treatment strategy for ischemic stroke.Graphic Abstract

Source: Journal of NeuroImmune Pharmacology - October 1, 2021 Category: Drugs & Pharmacology Source Type: research