Good reinnervation of motoneurons but poor recovery of gait after delayed as well as immediate sciatic nerve transplant in rats

Abstract

Surgeons agree that interrupted peripheral nerves should be reconstructed ‘soon’ to enable neural regeneration. Delayed nerve repair will result in impaired outcome, but experimental data on such detriment due to delay are scarce. In a quantitative study we transected the right sciatic nerve of 80 adult female Lewis rats (LEW/SsNHsd), transflected the proximal nerve stump into a muscle pouch and let the animals wait 0 (immediate repair), 3, 6, 9 and 12 months after axotomy, until reconstruction was performed with a 5‐mm long allograft from congenic age‐matched donors. All hosts were studied with two different methods. First, the functional outcome of sciatic nerve reconstruction was evaluated 4–12 weeks after transplant by walking track analysis, calculating de Medinaceli's Sciatic Functional Index (SFI). Second, 12 weeks after transplantation the fibular communal nerve and the soleus branch of the tibial nerve close to its muscle entry were cut and the proximal stumps labelled with the retrograde neuronal tracers DiI or Fast‐Blue. Fourteen days later the rats were perfused with formaldehyde, and the numbers of fluorescently labelled motoneurons were counted in 50 μm serial vibratome sections of the spinal cord. All measurements were done on coded material and codes broken only at the end of the study. Our results are clear‐cut and deeply disappointing. The SFI was around 0 (normal value) in all rats before transection of the sciatic nerve; expectedly dropped to −85 to −125 after denervation, but stayed at −108 to −130 up to 12 weeks after transplantation. No improvement of gait at all occurred after sciatic nerve transplant performed immediately or 3, 6, 9 or 12 months after denervation.This failure of functional recovery is not due to lack of regeneration, as the numbers of labelled motoneurons prove. In normal rats we have labelled 549 ± 83 motoneurons by DiI and Fast‐Blue. After immediate nerve repair we counted 533 ± 95 labelled motoneurons; after repair delayed for 12 months we still counted 474 ± 108 motoneurons that had regenerated. In all rats the labelled motoneurons were randomly interspersed with a complete lack of myotopic distribution. This misdirection of reinnervation sadly prevents recovery of motor function.