Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Neuroscience

Supervisor

Whitehead, Shawn N.

2nd Supervisor

Allman, Brian L.

Co-Supervisor

Abstract

Recent literature has supported a relationship between vascular disease and its role in the progression of cognitive impairment. Previous studies have demonstrated that white matter inflammation (WMI) in the brain is a common pathological outcome following stroke. Moreover, WMI has been shown to be the strongest predictor of cognitive decline following stroke. Finally, previous work in our lab has demonstrated, using a rodent model of striatal stroke, that WMI is correlated with post-stroke cognitive impairment. The current study aimed to further investigate the role of WMI in post-stroke cognitive impairment by utilizing a mediodorsal thalamic (MD) stroke model in the rat as well as a rat model of focal white matter inflammation. MD stroke in the mediodorsal thalamus was produced using an injection of the potent vasoconstrictor endothelin-1. Focal WMI was produced using injections of lipopolysaccharide into the corpus callosum. Behavioural flexibility was assessed using an operant set-shifting task to examine executive function, followed by post-mortem immunohistological analyses to assess WMI. We found that unilateral MD stroke produced a regressive behavioural phenotype, however no WMI was observed. Additionally, it was found that LPS-injected rats did not display traditional measures of behavioural inflexibility, however impairment was observed when assessing group error rates using a logarithmic regression model. The MD stroke model findings suggest that young rats may be more resilient to WMI than older rats. Additionally, the LPS model findings suggest that WMI may be implicated in causing executive dysfunction. Finally, this suggests a potential implication for anti-inflammatory treatment in the attenuation of cognitive impairment.

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