RT Journal Article
SR Electronic
T1 Post-stroke Intranasal (+)-Naloxone Delivery Reduces Microglial Activation and Improves Behavioral Recovery from Ischemic Injury
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0395-17.2018
DO 10.1523/ENEURO.0395-17.2018
VO 5
IS 2
A1 Jenni E. Anttila
A1 Katrina Albert
A1 Emily S. Wires
A1 Kert Mätlik
A1 Lisa C. Loram
A1 Linda R. Watkins
A1 Kenner C. Rice
A1 Yun Wang
A1 Brandon K. Harvey
A1 Mikko Airavaara
YR 2018
UL http://www.eneuro.org/content/5/2/ENEURO.0395-17.2018.abstract
AB Ischemic stroke is the leading cause of disability, and effective therapeutic strategies are needed to promote complete recovery. Neuroinflammation plays a significant role in stroke pathophysiology, and there is limited understanding of how it affects recovery. The aim of this study was to characterize the spatiotemporal expression profile of microglial activation and whether dampening microglial/macrophage activation post-stroke facilitates the recovery. For dampening microglial/macrophage activation, we chose intranasal administration of naloxone, a drug that is already in clinical use for opioid overdose and is known to decrease microglia/macrophage activation. We characterized the temporal progression of microglia/macrophage activation following cortical ischemic injury in rat and found the peak activation in cortex 7 d post-stroke. Unexpectedly, there was a chronic expression of phagocytic cells in the thalamus associated with neuronal loss. (+)-Naloxone, an enantiomer that reduces microglial activation without antagonizing opioid receptors, was administered intranasally starting 1 d post-stroke and continuing for 7 d. (+)-Naloxone treatment decreased microglia/macrophage activation in the striatum and thalamus, promoted behavioral recovery during the 14-d monitoring period, and reduced neuronal death in the lesioned cortex and ipsilateral thalamus. Our results are the first to show that post-stroke intranasal (+)-naloxone administration promotes short-term functional recovery and reduces microglia/macrophage activation. Therefore, (+)-naloxone is a promising drug for the treatment of ischemic stroke, and further studies should be conducted.