Item Details

abstract

Musculoskeletal injuries affect 1 in 2 adults over 18, contributing to significantly decreased quality of life and patient morbidity. This risk only increases as people get older, with ¾ of all adults over 65 experiencing muscle injury. This has an estimated economic impact of over $900 billion per year in the U.S. alone and rising. Limited treatment strategies exist to treat muscle trauma, primarily focused on pain management and preventing further injury, rather than restoration of contractile function. Compartment syndrome (CS) is one such severe muscle injury leaving patients with lasting functional deficits. Plants and plant-derived compounds have been studied throughout history for their medicinal properties. Polyphenols are organic compounds containing one or more phenol rings with antioxidant and anti-inflammatory properties found in high abundance in plants. Muscadine grape extract (MGE) is a mixed polyphenol compound derived from the skins and seeds of muscadine grapes. MGE has previously shown antioxidant properties and efficacy in reducing tumor proliferation and cardiac fibrosis. It has not been tested in the context of CS. This study utilizes a previously developed rat model of CS to evaluate the efficacy of MGE on skeletal muscle regeneration and inflammation. In this model, MGE leads to increased uninjured maximum force production on rat tibialis anterior (TA) muscles 2 weeks after administration. MGE also increased the percent recovery of force 2 weeks after CS injury. At 7 days post-CS, MGE decreased the half maximal relaxation time, suggesting alterations in calcium reuptake after contraction cessation. While no significant changes are seen in the number of Pax7+ SCs after CS injury due to MGE, there is a trend towards decreased numbers of this cell population 4 days after CS. While no changes in total or M2 macrophage populations were observed, MGE did induce a significant decrease in TA fibrosis 7 days after CS. No changes in cytokine protein production were seen, however there was a decrease in IL-6 mRNA production in vitro due to MGE administration on M1 macrophages. Future project directions and mechanism of action of MGE within injured and uninjured skeletal muscle tissue can be suggested by the myogenesis and NFκB pathway gene expression arrays and the bottom-up proteomics. These data reveal a role of MGE on intracellular calcium ion regulation, differential inflammation effects, and central metabolism changes.

subject

Compartment Syndrome

Inflammation

Muscle

Polyphenol

Rat

Regeneration

Criswell, Tracy L (advisor)

contributor

Poteracki, James Michael (author)

Cook, Katherine (committee member)

Jackson, John (committee member)

Seeds, Michael (committee member)

Soker, Shay (committee member)

date

2023-01-24T09:35:49Z (accessioned)

2023 (issued)

degree

Physiology and Pharmacology (discipline)

2025-01-23 (liftdate)

embargo

2025-01-23 (terms)

identifier

http://hdl.handle.net/10339/101776 (uri)

language

en (iso)

publisher

Wake Forest University

title

THE ROLE OF MUSCADINE GRAPE EXTRACT ON SKELETAL MUSCLE 1 REGENERATION

type

Dissertation