Year of Publication

2017

Degree Name

Master of Science (MS)

Document Type

Master's Thesis

College

Medicine

Department

Medical Sciences

First Advisor

Dr. M. Paul Murphy

Abstract

Cleaved fragments of the extracellular matrix protein perlecan have been shown to promote neuroprotection and repair after ischemic stroke. The cysteine proteases cathepsin B and L as well as the metalloprotease bone morphogenic protein 1 (BMP-1) are capable of releasing the biologically active C-terminal laminin-like globular domain (LG3) of perlecan. Exercise, a known method of reducing stroke risk and severity, has been shown to increase the expression of some proteases associated with perlecan processing. Using a transient distal middle cerebral artery occlusion (MCAo) model for focal ischemic stroke we show that while 7 days of running only slightly decreased infarct volume, BMP1 and perlecan (HSPG2) RNA expression in skeletal muscle was significantly increased in 3-month-old male wild type C57/BL6 mice. Moreover, elevated levels of BMP1 RNA were still detectable after 3 days of detraining, suggesting a prolonged effect of exercise on BMP1 expression. Levels of LG3 in the blood were below the limit of detection in the current study, however it is likely that a more sensitive method would enable analysis of serum. These preliminary findings suggest that LG3 could be a molecular mediator of neuroprotection afforded by exercise though further studies are required.

Digital Object Identifier (DOI)

https://doi.org/10.13023/ETD.2017.327

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