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THESIS PROPOSAL
for the Doctoral Program at the
Medical University of Vienna
Working title (without abbreviations)
The Effects of selective Nerve Transfers on the Motor Unit
acad. degree, first name, last name
(field of graduate study)
E-mail:
Dr. ___________________________________________________________________________
med. univ. Konstantin Bergmeister
___________________________________________________________________________
Clinical Neuroscience - Reconstructive Surgery
___________________________________________________________________________
[email protected]
_______________________________________
Location:
Institute and address where thesis will be performed
Christian Doppler Laboratory for Restoration of Extremity Function, Division of Plastic & Reconstructive
Surgery, Department of Surgery, Medical University of Vienna, Austria
Währigergürtel 18-20
1090 Wien
Supervisor:
Name and address of supervisor
Ao. Univ. Prof. Oskar C. Aszmann
Christian Doppler Laboratory for Restoration of Extremity Function, Division of Plastic & Reconstructive
Surgery, Department of Surgery, Medical University of Vienna, Austria
Währigergürtel 18-20
1090 Wien
Supported by:
Name and address of granting institution, project, etc.
Christian Doppler Research Foundation
Boltzmanngasse 20 1090 Wien
Project: Christian Doppler Laboratory for Restoration of Extremity Function
Date:
April, 2014
month, year
Thesis proposal for the Doctoral Program
Signature of the applicant
1/14
Summary and aim
Background:
Muscles are the effectors of all human interaction with the environment. The smallest functional unit of the muscle is the
motor unit [MU], consisting of the motor neuron [MN] which connects to the motor endplate and thereby innervates motor
fibers. Selective nerve transfers [SNT] have become an important tool for the restoration of extremity function [1]. In this
procedure the composition of the motor unit is altered as the MN is connected to motor endplates and fibers of different
qualities.
Clinical experience shows that SNTs provide good outcome, however with variable coordination. We assume that this
results from the alteration of the motor unit components and thereby altered muscle recruitment. Additionally, possible
hyper-reinnervation of the muscle might lead to polyneuronal innervation (polyinnervation) of motor endplates. This may
further compromise the size principle recruitment, which is essential for movement control [2].
Objectives:
The main objective of our study is to investigate the effects of SNT on motor units and muscle composition. In detail, we
focus on these aims:
1. Structure: Effect of SNT on the motor unit and muscle composition
2. Time frame: Changes of the effect over time
3. Function: Motor unit recruitment after SNT
Methods and Working Plan:
In two trials (adult and neonatal) a SNT is applied by transferring a nerve with a very high innervation density to a single
muscle-branch of a poorly innervated muscle (ulnar nerve [UN] to motor branch of caput longum bicipitis brachi [CLBB]).
This leads to hyperreinnervation and possibly polyinnervation of this muscle, and thus alters the motor unit pool.
Both trials consists of three sub-trials: a time trial, a retrograde labeling trial and a imaging trial. In the first sub-trial, the
time-trial, the effect of the SNT is assessed after 2,6 and 12 weeks. For functional evaluation (motor unit recruitment) we
use functional muscle testing, where the nerve is directly stimulated and the maximum force and number of motor units is
evaluated [4-5]. For histological evaluation, we use antibody fiber typing, to calculate the proportions of the different fiber
types [6]. In the retrograde labeling trial, we use a double retrograde labeling procedure to determine the ratio number of
motor neurons that innervate the muscle compared to the numbers that possibly could innervate the muscle [7]. In the last
sub-trial, the imaging trial, the Thy1-GFP rat is utilized to analyze the muscle's neuromuscular junction [8-10]. This
transgenic rat expresses green fluorescent protein along its axon. By application of alpha-bungaro-toxin we can visualize
the neuromuscular junction and calculate the degree of polyinnervation [9-10].
Originality and Relevance:
So far only a few authors have addressed this topic. The cofounder of targeted muscle reinnervation [TMR], TA Kuiken,
investigated the effect of hyper-reinnervation on rat skeletal muscle in 1995 [3], yet without the methods nowadays
available for muscle analysis. TMR is of great importance for improved prosthesis control. The identification of its effects
on the muscle, could possibly provide better long-term movement control and optimize anatomical rewiring.
Thesis proposal for the Doctoral Program
2/14