Femke Mathot

General introduction 13 1 BACKGROUND The brain and the spinal cord together fulfill the role of the central nervous system. In this system, incoming signals are processed and converted into concrete sensations like pain or touching. This system also forms and sends commands to their targets leading to desired actions like muscle contraction, enabling us to walk, talk or eat. The peripheral nervous system facilitates the transfer of the incoming and outgoing signals between the central nervous system and its target (organs). Accurate sensation and muscle control are therefore completely dependent on a fully functional peripheral nervous system. Due to its crucial function, peripheral nerve injuries can be life-changing events, impacting a patients function, autonomy and quality of life. 1, 2 They occur in 3% of all extremity traumas, most commonly as a result of motor vehicle accidents and penetrating traumas. 3 The socio- economic impact of peripheral nerve injuries is so substantial that maximum efforts should be made to obtain maximal recovery rates. 4 This thesis aims to fulfill a role in the efforts to improve outcomes of peripheral nerve injuries. ANATOMY The peripheral nervous system is composed of an extensive network of peripheral nerves. The anatomy of a peripheral nerve is illustrated in figure 1 . A peripheral nerve is a bundle containing a varying amount of fascicles that are held together by the epineurium, a layer of connective tissue. These fascicles intermingle with each other along the course of the nerve. Each fascicle consists of a bundle of axons, encompassed by layers of perineurial cells and collagen, the perineurium. 5 Each individual axon is surrounded by endoneurium. 6 These extracellular matrix components (epineurium, perineurium and endoneurium) are pivotal in axon guidance and triggering intracellular signals, which should be taken into account when restoring peripheral nerve injuries. 7 Axons are long, tubular offshoots of nerve cell bodies (neurons). Most neurons have multiple other cytoplasm-protrusions besides the axon, which are much shorter than axons. These so called dendrites receive stimuli from other cells and if stimuli are strong enough, they are converted in the cell body to an electrical stimulus (action potential) which is transmitted by the axon. Most axons branch towards their ends (axon terminals), making connections with other neurons or target cells by synaptic junctions. Action potentials are transmitted through these junctions by the release of neurotransmitters. At a neuromuscular junction this release causes activation of muscle fibers, resulting in muscle contraction. The location of the neuron cell-body and the synaptic junctions of its axon determines its function. 6, 8 Oxygen and other essential nutrients for the cells and their processes in the peripheral nervous system are provided by diffusion from intrinsic and extrinsic vessels, the vasa nervorum. The extrinsic vasculature runs along the surface of the nerve, supplying the epineural and perineural regions. The internal vasculature is located inside the fascicles, the endoneurial compartment. 9,