Treatment With Nimodipine or FK506 After Facial Nerve Repair Neither Improves Accuracy of Reinnervation Nor Recovery of Mimetic Function in Rats

Abstract

PurposeNimodipine and FK506 (Tacrolimus) are drugs that have been reported to accelerate peripheral nerve regeneration. We therefore tested these substances aiming to improve the final functional outcome of motoric reinnervation after facial nerve injury.MethodsIn 18 female rats, the transected facial nerve was repaired by an artificial nerve conduit. The rats were then treated with either placebo, nimodipine, or FK506, for 56 days. Facial motoneurons were pre-operatively double-labeled by Fluoro-Gold and again 56 days post-operation by Fast-Blue to measure the cytological accuracy of reinnervation. The whisking motion of the vibrissae was analyzed to assess the quality of functional recovery.ResultsOn the non-operated side, 93–97% of those facial nerve motoneurons innervating the vibrissae were double-labeled. On the operated side, double-labeling only amounted to 38% (placebo), 40% (nimodipine), and 39% (FK506), indicating severe misdirection of reinnervation. Regardless of post-operative drug or placebo therapy, the whisking frequency reached 83–100% of the normal value (6.0 Hz), but whisking amplitude was reduced to 33–48% while whisking velocity reached 39–66% of the normal values. Compared to placebo, statistically neither nimodipine nor FK506 improved accuracy of reinnervation and function recovery.ConclusionDespite previous, positive data on the speed and quantity of axonal regeneration, nimodipine and FK506 do not improve the final functional outcome of motoric reinnervation in rats.

Treadmill training of rats after sciatic nerve graft does not alter accuracy of muscle reinnervation

“…Nerve transection, however, interrupts all basal lamina tubes, leads to the mis-sprouting of axonal branches, and destroys myotopic reinnervation ( Figure 1 ) that cannot be compensated by central plasticity ( 75 ). In particular, double-labeled neurons, that were never observed in intact animals, simultaneously innervate fibers of the flexor and extensor muscles, and thus cause an antagonistic inhibition, also referred to as auto- or post-paralytic syndrome ( 3 – 6 , 24 , 27 , 28 , 76 ).…”

“…The ultimate goal of nerve repair is the morphological and functional recovery of the motor and sensory systems. Numerous investigations were conducted in either the sciatic nerve or the common fibular [peroneal] nerve to estimate the quality and quantity of regeneration and recovery of function using retrograde neuronal labeling, stereology, and electrophysiology (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13), walking track measurements (5,(13)(14)(15)(16)(17)(18), and video analysis of gait methodologies (10,(19)(20)(21)(22).…”

Advances in optical molecular imaging for neural visualization

“…FG is widely considered the most reliable method for preclinical retrograde neuronal labeling due to its bright fluorescence, efficient labeling, lack of diffusion to neighboring cells, ability to label cell body cytoplasm and dendrites, and resistance to fading, suitable for targeted deep imaging of the nervous system ( Schmued, 2016 ). Its visibility under ultraviolet light has been extensively utilized in animal research that involves brainstem-related injuries ( Barham et al, 2022 ). Through experimentation, it was discovered that FG’s two-photon excitation spectrum ranges from 720 to 990 nm.…”