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58 posters, 14 topics, 4 sessions, 188 authors, 62 institutions

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PSRC 69th Annual Meeting 2024

May 16-19, 2024 | The Westin Copley Place, Boston, MA

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EP43

Longitudinal Nerve And Muscle Changes In A Murine Model Of Chronic Nerve Compression

Poster Presenter

Jagmeet Arora

Part of Topic

Nerve

LONGITUDINAL NERVE AND MUSCLE CHANGES IN A MURINE MODEL OF CHRONIC NERVE COMPRESSION

 

Introduction

•Chronic peripheral nerve compression (CNC) has the potential to cause substantial morbidity with severity often depending on the duration of compression.
•Previous murine models have examined CNC for short durations.
•In this study, we characterize longitudinal nerve, muscle, and genetic changes over 52 weeks of nerve compression in a murine model.
 
Methods
•Three groups of increasing compression duration:
•16 weeks
•32 weeks
•52 weeks
•To induce compression, a silastic tube was placed around the left sciatic nerve with the contralateral nerve as a paired control.
•After compression, the following was collected and analyzed:
•Electrodiagnostic data
•Tibialis anterior and Gastrocnemius muscles
•Sciatic nerves
 

Results

Figure 1: Electrodiagnostic data. (A) Decreased nerve conduction velocity at 16w (p=0.002), 32w (p=0.009), and 52w (p=0.001). (B) Lengthened action potential duration that normalized over time (16w: p=0.003 || 32w: p=0.03 || 52w: p=0.60). 

Figure 2: Muscle PCR Analysis. Increased expression of atrophy genes at 16 weeks (FOXO3: FC=1.39; p=0.02 || Atrogin-1: FC=1.55; p=0.02 || MuRF1: FC=1.70; p=0.002) with a return to baseline by 32 weeks. Myogenic markers were initially decreased at 16 weeks (MyoD: FC=0.62; p=0.02 || MyoG: FC=0.70; p=0.07). However, MyoG demonstrated increased expression from 16 weeks to 52 weeks (16w: FC=0.75 vs. 52w: FC= 2.1, p< 0.001) with the most significant increase, between consecutive timepoints, occurring from 32 weeks to 52 weeks (32w: FC=1.241 vs. 52w: FC=2.095, p=0.02). 

Figure 3: Compared to the (A) control group, nerve histology demonstrated a progressive increase in the interaxon space that intensified with longer compression from (B) 16 weeks to (C) 32 weeks to (D) 52 weeks. Mice experienced significant reductions in axon density from 16w to 52w (p=0.01) with the most significant reduction, between consecutive timepoints, from 16 weeks to 32 weeks. Total fiber cross sectional area was significantly reduced at 16w (p=0.009) and 52w (p=0.03).


Conclusions

•CNC in a longitudinal murine model of nerve compression causes decreased nerve conduction speeds, reductions in axon density, and changes to axon structure.
•Axonal changes occur between 16 weeks to 32 weeks, with some recovery of nerve function over time.
•Muscular remodeling occurs between 32-52 weeks, with gene expression revealing an initial increase in atrophy markers with a compensatory increase in myogenic markers.
 
Future Directions
•Evaluate nerve histology proximal and distal to sciatic nerve compression
•Characterize neuromuscular junction morphology to improve understanding of muscle changes
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