Factors limiting motor recovery after facial nerve transection in the rat: combined structural and functional analyses

Abstract

It is believed that a major reason for the poor functional recovery after peripheral nerve lesion is collateral branching and regrowth of axons to incorrect muscles. Using a facial nerve injury protocol in rats, we previously identified a novel and clinically feasible approach to combat axonal misguidance--the application of neutralizing antibodies against neurotrophic factors to the injured nerve. Here, we investigated whether reduced collateral branching at the lesion site leads to better functional recovery. Treatment of rats with antibodies against nerve growth factor, brain-derived neurotrophic factor, fibroblast growth factor, insulin-like neurotrophic factor I, ciliary neurotrophic factor or glial cell line-derived neurotrophic factor increased the precision of reinnervation, as evaluated by multiple retrograde labelling of motoneurons, more than two-fold as compared with control animals. However, biometric analysis of vibrissae movements did not show positive effects on functional recovery, suggesting that polyneuronal reinnervation--rather than collateral branching --may be the critical limiting factor. In support of this hypothesis, we found that motor end-plates with morphological signs of multiple innervation were much more frequent in reinnervated muscles of rats that did not recover after injury (51% of all end-plates) than in animals with good functional performance (10%). Because polyneuronal innervation of muscle fibres is activity-dependent and can be manipulated, the present findings raise hopes that clinically feasible and effective therapies could be soon designed and tested.

Focal release of neurotrophic factors by biodegradable microspheres enhance motor and sensory axonal regeneration in vitro and in vivo

“…Although this results could seem contradictory, it has been reported that neurons initially generate several axonal sprouts after axotomy (Mackinnon et al, 1991), and even at long term each neuron may maintain more than a single regenerated axonal branch (Gómez et al, 1996;Jenq & Coggeshall, 1985). Furthermore, more regenerated axons (sprouts) do not necessarily indicate more neurons regenerating (Piquilloud et al, 2007) and may be also considered deleterious in terms of functional recovery (Guntinas-Lichius et al, 2005). Hence, the increase of MF in the NGF groups would be in accordance with other studies that describe an important role of NGF on axonal sprouting (Diamond et al, 1987;Gloster et al, 1992;Ruiz et al, 2004).…”

Experimental studies on post-transectional facial nerve regrowth and functional recovery of paralyzed muscles of the face in rats and mice

“…Streppel et al 21 hypothesized that that the aberrant axonal branching could, at least in part, be due to the The subsequent biometric analysis of vibrissae movements however, did not show positive effects on functional recovery suggesting that polyneuronal reinnervation of the motor end-plates-rather than collateral branching -may be the critical limiting factor. In support of this hypothesis, Guntinas-Lichius et al 28 found that motor end-plates with morphological signs of multiple innervation were much more frequent in reinnervated muscles of rats which did not recover after injury (51% of all end-plates) compared to animals with good functional performance (10%).…”

“…[20][21][22]27 (iv) combined immunostaining of axons (anti-neuronal class III β-tubulin) and histochemical staining of the neuromuscular junctions (AlexaFluor 488-conjugated α-bungarotoxin) to estimate the quality of target muscle reinnervation. 28,29 The results described in this review reflect our efforts to reduce collateral axonal branching by application to the Trying to reduce the intramuscular (terminal) axonal sprouting we proved the effect of (i) intraoperative electrical stimulation of the transected nerve, (ii) post-operative electrical stimulation of the denervated muscles, (iii) mechanical stimulation of the paralyzed mucles after facial-facial anastomosis (FFA), hypoglossal-facial anastomosis (HFA) and after interpositional nerve grafting (IPNG) of the facial nerve.…”

“…Thus, there was a complete lack of myotopic organization, increased total numbers of projecting motoneurons and a consistently elevated Although post-lesional polyinnervation of the end-plates has been claimed to be transient, 40 accumulating evidence suggests that it persists after establishment of nerve-muscle contacts 32,41,42,[83][84][85][86][87] and previous work indicates that it has a deleterious effect on recovery of facial motor function. 28 In intact animals, all motor endplates of the largest vibrissal muscle, the levator labii superioris, were monoinnervated (Figure 5c). After facial nerve transection and suture, 53% were polyinnervated, i.e.…”

Melatonin and its therapeutic actions on peripheral nerve regeneration

“…It has been suggested that correct re-innervation of the neuromuscular junctions, rather than collateral axonal branching at the lesion site, may be the critical limiting factor for recovery of function after peripheral nerve injury [17]. Chang et al [7] recently demonstrated that re-innervated motor end plates (as labelled by PGP 9.5 and a-bungarotoxin) following peripheral nerve injury was much higher in the animals receiving melatonin treatment when compared to that of saline-treated ones.…”