Date of Graduation

5-2019

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Kinesiology (PhD)

Degree Level

Graduate

Department

Health, Human Performance and Recreation

Advisor/Mentor

Washington, Tyrone A.

Committee Member

Greene, Nicholas P.

Second Committee Member

Wolchok, Jeffrey C.

Third Committee Member

Dridi, Sami

Keywords

Extracellular Matrix; Fibrosis; Inflammation; Injury; Muscle; Recovery; Regeneration; Satellite Cell

Abstract

Volumetric muscle loss affects both military and civilian persons. The hallmark of this injury is incomplete muscle regeneration, excessive fibrosis, and chronic inflammatory signaling resulting in permanent functional loss. Since permanent functional loss drastically reduces quality of life, many studies have been conducted to improve force recovery. Current scientific literature considers a repair strategy of either devitalized scaffolds infused with growth factors or viable tissue plus activating factors to be the more promising interventions for optimal force recovery. PURPOSE The purpose of this study is to incorporate autologous repair and physical activity and observe the effects of muscle force recovery and regeneration, fibrosis, and inflammatory signaling. METHODS 32 male Sprague-Dawley rats had 20% of their LTA removed then replaced to act as autologous repair. Half of the rats utilized wheel running, and at 2 and 8 weeks, the autologous tissue was excised from the LTA from both wheel running and sedentary rats. Electrophysiology measured peak tetanic force. Histology was used to measure CSA, centrally-located nuclei, percent of non-contractile tissue, and collagen deposition. qRT-PCR evaluated the gene expression of myogenic, ECM remodeling, and inflammatory signaling markers. RESULTS Wheel activity promoted force recovery at 2 weeks, but both groups had similar force output by 8 weeks. Myogenic gene expression did not differ in the LTA between groups at either time point. Wheel activity caused differential effects of collagen deposition in the defect and intact LTA tissue. Wheel activity differentially altered ECM remodeling markers at the 2 and 8 week time points in the wheel activity and sedentary groups. Wheel activity appeared to attenuate inflammatory signaling markers at 2 weeks, but showed evidence of a pro-inflammatory environment by 8 weeks. DISCUSSION Wheel activity promoted early beneficial responses in force recovery, ECM remodeling, and inflammatory signaling markers. These responses were not evident by 8 weeks, however, the same early patterns of these markers were observed at 8 weeks in the sedentary group. Force recovery equalizes by 8 weeks with autologous repair but is expedited using wheel activity.

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