Functional and Molecular Characterization of a Novel Traumatic Peripheral Nerve–Muscle Injury Model

Abstract

Traumatic injuries to human peripheral nerves are frequently associated with damage to nerve surrounding tissues including muscles and blood vessels. Currently, most rodent models of peripheral nerve injuries (e.g., facial or sciatic nerve) employ surgical nerve transection with scissors or scalpels. However, such an isolated surgical nerve injury only mildly damages neighboring tissues and weakly activates an immune response. In order to provide a rodent nerve injury model accounting for such nerve-associated tissue damage and immune cell activation, we developed a drop tower-based facial nerve trauma model in mice. We compare nerve regeneration in this novel peripheral nerve trauma model with the established surgical nerve injury along several parameters. These include gene expression, histological and functional facial motoneuron (FMN) regeneration, facial nerve degeneration, immune cell activation and muscle damage. Regeneration-associated genes (RAGs; e.g., Atf3) were strongly induced in FMNs subjected to traumatic and surgical injury. Regeneration of FMNs and functional recovery of whisker movement were faster in traumatic versus complete surgical injury, thus cutting down experimentation time. Wallerian degeneration of distal nerve stumps was readily observed in this novel trauma injury model. Importantly, drop tower-inflicted facial nerve injury resulted in muscle damage, activation of muscle satellite cell markers (PAX7) and pronounced infiltration of immune cells to the injury site only in this model but not upon surgical nerve transection. Thus, we provide a novel rodent PNS trauma model that can be easily adopted to other PNS nerves such as the sciatic nerve. Since this nerve trauma model replicates multiple tissue damage frequently encountered in clinical routine, it will be well suited to identify molecular and cellular mechanisms of PNS nerve repair in wild-type and genetically modified rodents.

Interference with SRF expression in skeletal muscles reduces peripheral nerve regeneration in mice

“…Before nerve injury, whisker pro-and retraction is typically highly synchronous between the two whisker pads. Indeed, as seen before 23 , 100 Hz sequences of whisker movement was almost identical between both sides (Fig. 5A,B).…”

“…This was done by quantifying the transport efficacy of fluorescently labelled retrograde tracer molecules along the injured axons ( Fig. 3 23,24 ). Since the various FN branches target different muscle groups in the face, FN motoneurons in the brainstem nuclei are organized in a topographic map.…”

“…3N,O). Immediately after injury, this transport is impaired since the axonal transport route is compromised by the lesion 23,24 . However, at 21 dpi some axons have already regenerated and navigated towards new target areas which reconstitutes the transport way for tracer molecules and gives a quantitative read-out for axon regeneration (Fig.…”

“…Unilateral FN injury silences such whisker movement immediately after axotomy. In subsequent days and weeks, recovery of whisker movement can be monitored by high speed camera recording and is used as a read-out for successful functional axon regeneration 23 .…”

Sequence‐Optimized Peptide Nanofibers as Growth Stimulators for Regeneration of Peripheral Neurons

“…However, this does not automatically result in the recovery of physiological function of injured nerves. In order to analyze whether nerve regeneration also enhanced function of the neuromuscular unit controlling whisker movement, we performed timelapse‐videomicroscopy as reported by others and us before ( Figure ). Here, individual vibrissae of both sides of the animals were recorded before and at several timepoints after injury (Figure A).…”