VAGUS NERVE REGENERATIVE CAPACITY AND STRATEGIES TO PROMOTE ITS FUNCTIONAL RECOVERY IN RODENT MODELS

The vagus nerve is a mixed nerve comprising sensory, motor, and parasympathetic fibers that plays a central role in regulating essential physiological functions, including respiration, heart rate, gastrointestinal motility and immune response. Therefore, injuries of the vagus nerve can lead to severe dysfunctions.
Although peripheral nerves are able to regenerate after injury, the regenerative capacity of autonomic fibers remains insufficiently characterized. Therefore, the aim of this study was to explore the regenerative potential of different fiber populations within the vagus nerve. We crushed the left cervical vagus nerve in transgenic mice expressing red fluorescence in cholinergic (Chat+) neurons (Chat-Cre/Td-Tomato) or Npy2r+ neurons (Npy2r-Cre/Td-Tomato), enabling the identification of motor and parasympathetic fibers or a specific subtype of sensory axons, respectively. Functional recovery of autonomic control was evaluated by assessing cardiac function through electrocardiographic recordings.
Nine days post-injury, 17 mm distal to the crush site, the amount of regenerating Npy2r axons was close to basal values. In contrast, the number of cholinergic axons was significatively lower (30%). At this distance, cholinergic axons are mainly parasympathetic, since the motor axons inervate the larynx branches proximaly.
To compare autonomic and somatic regeneration, we analyzed cholinergic fiber regeneration in the tibial nerve after sciatic nerve crush. Preliminary results indicate that motor axon regeneration at 17 mm is even lower than that observed for parasympathetic fibers.
Overall, these findings highlight distinct regenerative responses among vagal fiber populations and emphasize the importance of evaluating each group independently to improve therapeutic strategies.