Polyethylene glycol administration in an animal model of focal ischemic stroke

Alicia M Altizer, Purdue University

Abstract

In the United States alone, approximately 700,000 people will suffer a first or recurrent stroke this year. Of those, approximately 275,000 will die, making stroke America's third largest killer. Further, stroke is a leading cause of adult disability with survivors experiencing sensory, motor, and cognitive deficits that can lead to a lack of independence and a reduced quality of life. Here, we test whether polyethylene glycol (PEG), a biocompatible polymer used successfully in other injury models, can promote anatomical and behavioral recovery from focal cerebral ischemia (i.e., stroke) when administered two hours following middle cerebral artery occlusion (MCAo). Behavior was assessed using a rotarod apparatus and an open-field exploration box. Additionally, the ischemic lesion was quantified following histological staining by triphenyltetrazolium chloride (TTC), and a viable cell count was determined utilizing the MTT assay. Based on the behavioral data, no clear conclusion can be discerned. Independently, the rotarod data suggest that PEG was successful. With the exception of day 2, the PEG-treated animals displayed superior performance for both top speed and time in comparison to injured, control animals. By day 7, the differences between groups were significant. However, results from the exploration box question the usage of PEG as administered. Across all measures (e.g., total beam breaks, distance traveled), uninjured animals performed significantly better than injured animals, regardless of drug treatment or time of testing (light vs. dark cycle). The injured, PEG-treated and injured, control animals did not differ significantly. Results of the histological examination demonstrate that a significant difference in ischemic volume existed between PEG-treated and control animals, with the PEG-treated animals exhibiting more ischemia. Further, a comparison of percent ischemia between injured groups revealed a nearly significant difference. Finally, comparisons between adjusted absorbances and percent adjusted absorbances for injured tissues, as quantified by the MTT assay, revealed no significant differences between treatment groups. Together, the results demonstrate that PEG administration, at the given dosage and time, did not significantly advance anatomical or behavioral recovery, with the exception of the rotarod data. Thus, PEG does not appear to afford considerable neuroprotection within the experimental parameters of this MCAo injury model.

Degree

Ph.D.

Advisors

Borgens, Purdue University.

Subject Area

Neurosciences

COinS