The therapeutic potential of gamma-burst oscillations (GBOs) delivered by low-field magnetic stimulation (LFMS) in a rodent model of focal cortical ischemic stroke.
Date
2019-01-10
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
ORCID
Type
Thesis
Degree Level
Masters
Abstract
Many stroke survivors are affected by emotional and cognitive impairments that are difficult to treat. The current study uses a focal cortical ischemic stroke model called pial vessel disruption (PVD), which results in a non-reperfusion lesion in the right hemisphere. Previous studies have shown that PVD increases adenosine signalling, leading to the persistent stimulation and subsequent internalization of the adenosine A1 receptor (A1R), as well as the compensatory upregulation of the adenosine A2 receptor (A2AR) in the hippocampus. This adenosine receptor remodeling decreases cell surface expressions of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor subtypes GluA1 and GluA2, thereby impairing hippocampal long-term potentiation (LTP). Moreover, cognitive deficits along with depression- and anxiety-like behaviours are demonstrated by rats following PVD. To better understand how neural oscillations affect post-PVD cell signalling and behaviour, LFMS delivering GBOs (40 Hz) was applied once-daily for three days following PVD. The literature suggests that ischemic stroke desynchronizes hippocampal gamma oscillations (30-80 Hz). This range of neural frequencies underlie higher cognitive processes such as learning and memory. Hippocampal-dependent cognition is crucial for encoding healthy emotional memories. Thus, LFMS may be normalizing adenosine signalling and resynchronizing endogenous gamma oscillations to have an overall therapeutic effect on post-PVD behavioural changes. Indeed, three LFMS treatments improved various aspects of depression- and anxiety-like behaviours, as well as hippocampal-dependent spatial memory in rats that underwent PVD. Moreover, LFMS equalized LTP between the ipsilateral and contralateral hippocampi and protected both hemispheric regions from cell death and neurodegeneration. Based on these results, LFMS may have a neuroprotective effect through either decreasing extracellular adenosine concentrations, preventing persistent A1R stimulation, or decreasing the compensatory upregulation of A2AR in the hippocampus following PVD.
Description
Keywords
ischemic stroke, gamma-burst oscillations, low-field magnetic stimulation, gamma oscillations, pial vessel disruption, adenosine, A1R, A2AR, GluA1, GluA2, post-stroke depression, post-stroke anxiety, post-stroke cognitive impairments
Citation
Degree
Master of Science (M.Sc.)
Department
Pharmacology
Program
Pharmacology