Nerve Repair Site Research Articles

C3 peptide promotes axonal regeneration and functional motor recovery after peripheral nerve injury.

Peripheral nerve injuries are frequently seen in trauma patients and due to delayed nerve repair, lifelong disabilities often follow this type of injury. Innovative therapies are needed to facilitate and expedite peripheral nerve regeneration. The purpose of this study was to determine the effects of a 1-time topical application of a 26-amino-acid fragment (C3156-181), derived from the Clostridium botulinum C3-exoenzyme, on peripheral nerve regeneration in 2 models of nerve injury and repair in adult rats. After sciatic nerve crush, different dosages of C3156-181 dissolved in buffer or reference solutions (nerve growth factor or C3bot-wild-type protein) or vehicle-only were injected through an epineurial opening into the lesion sites. After 10-mm nerve autotransplantation, either 8.0 nmol/kg C3156-181 or vehicle were injected into the proximal and distal suture sites. For a period of 3 to 10 postoperative weeks, C3156-181-treated animals showed a faster motor recovery than control animals. After crush injury, axonal outgrowth and elongation were activated and consequently resulted in faster motor recovery. The nerve autotransplantation model further elucidated that C3156-181 treatment accounts for better axonal elongation into motor targets and reduced axonal sprouting, which are followed by enhanced axonal maturation and better axonal functionality. The effects of C3156-181 are likely caused by a nonenzymatic down-regulation of active RhoA. Our results indicate the potential of C3156-181 as a therapeutic agent for the topical treatment of peripheral nerve repair sites.Electronic supplementary materialThe online version of this article (doi:10.1007/s13311-011-0072-y) contains supplementary material, which is available to authorized users.

Histomorphometric changes in repaired mouse sciatic nerves are unaffected by the application of a scar-reducing agent.

Microsurgical repair of transected peripheral nerves is compromised by the formation of scar tissue and the development of a neuroma, thereby limiting the success of regeneration. The aim of this study was to quantify histomorphometrically the structural changes in neural tissue that result from repair, and determine the effect of mannose-6-phosphate (M6P), a scar-reducing agent previously shown to enhance regeneration. In anaesthetised C57-black-6 mice, the left sciatic nerve was sectioned and repaired using four epineurial sutures. Either 100 μL of 600 mm M6P (five animals) or 100 μL of phosphate-buffered saline (placebo controls, five animals) was injected into and around the nerve repair site. A further group acted as sham-operated controls. After recovery for 6 weeks, the nerve was harvested for analysis using light and electron microscopy. Analysis revealed that when compared with sham controls, myelinated axons had smaller diameters both proximal and distal to the repair. Myelinated axon counts, axonal density and size all decreased across the repair site. There were normal numbers and densities of non-myelinated axons both proximal and distal to the repair. However, there were more Remak bundles distal to the repair site, and fewer non-myelinated axons per Remak bundle. Application of M6P did not affect any of these parameters.

The effect of Mannose-6-Phosphate on recovery after sciatic nerve repair

We have determined the effect of applying Mannose-6-Phosphate (M6P), a scar reducing agent, to a site of sciatic nerve repair. In anaesthetised C57-Black-6 mice, the left sciatic nerve was sectioned and repaired using 4 epineurial sutures. Either 100μl of 600mM Mannose-6-Phosphate (29 animals), or 100μl of phosphate buffered saline as a placebo control (29 animals), was injected into and around the nerve repair site. A further group acted as sham-operated controls. After 6 or 12weeks of recovery the extent of regeneration was assessed electrophysiologically and the percentage area of collagen staining at the repair site was analysed using picrosirius red and image analysis. Gait analysis was undertaken pre-operatively and at 1, 3, 6, 9 and 12weeks postoperatively, to assess functional recovery. At 6weeks the compound action potentials recorded from the regenerated nerves in the M6P group were significantly larger than in the placebo controls (P=0.015), and the conduction velocities were significantly faster (P=0.005), but there were no significant differences between these groups at 12weeks. Gait analysis suggested better early functional recovery in the M6P group. In both repair groups there was a significant reduction in collagen staining between 6 and 12weeks, suggestive of scar remodelling. We conclude that the normal scar remodelling process aids long term recovery in repaired nerves. Administration of 600mM M6P to the nerve repair site enhances nerve regeneration and functional recovery in the early stages, and may lead to improved outcomes.

A comparison between the effects of three potential scar-reducing agents applied at a site of sciatic nerve repair

We have investigated the effect of three potential scar-reducing agents applied at a sciatic nerve repair site in C57-black-6 mice. Under anaesthesia the nerve was transected, repaired using four epineurial sutures, and 100 μl of either triamcinolone acetonide (1 mg/100 μl), an interleukin-10 peptide fragment (125 ng/100 μl or 500 ng/100 μl) or mannose-6-phosphate (M6P, 200 mM or 600 mM) was injected into and around the nerve. After 6 weeks the extent of regeneration was assessed electrophysiologically by determining the ratio of the compound action potential (CAP) modulus evoked by electrical stimulation of the nerve 2 mm distal or proximal to the repair site. The conduction velocity of the fastest components in the CAP was also calculated. The percentage area of collagen staining (PAS) at the repair site was analysed using Picrosirius Red and image analysis. Comparisons were made with a placebo group (100 μl of phosphate buffered saline) and sham-operated controls. The median CAP modulus ratio in the 600 mM M6P group was 0.44, which was significantly higher than in the placebo group (0.24, P=0.012: Kruskal–Wallis test). Conduction velocities were also faster in the 600 mM M6P group (median 30 m s −1) than in the placebo group (median 27.8 m s −1; P=0.0197: Kruskal–Wallis test). None of the other treated groups were significantly different from the placebo, and all had significantly lower CAP ratios than the sham controls ( P<0.05). All repair groups had a significantly higher PAS for collagen than sham controls. We conclude that the administration of 600 mM mannose-6-phosphate to a nerve repair site enhances axonal regeneration.

Innervation of parasympathetic postganglionic neurons and bladder detrusor muscle directly after sacral root transection and repair using nerve transfer

This is a continuation of studies examining the effectiveness of root repairs and nerve transfers for bladder reinnervation. Our previous retrograde fluorogold tracing studies from the bladder to the spinal cord found regrowth of axons from the spinal cord through the nerve repair site to the bladder which was confirmed electrophysiologically [Ruggieri et al. J Neurotrauma 25:214–24, 2006]. The current study determines whether the pattern of axonal regrowth from the repaired nerves or roots to the bladder is different between the surgical reanastomosis methods. The canine bladder was denervated by transection of all nerve roots from the sacral spinal cord mediating bladder contraction. Reinnervation surgeries included end-on-end repair of transected sacral ventral roots, transfer of coccygeal to sacral ventral roots(CGNT),or transfer of genitofemoral to pelvic nerves(GFNT). Postmortem dialkylcarbocyaninedye tracing with Neurotrace DiI from the distal pelvic nerve to the bladder wall, combined with PGP9.5 neuronal immunohistochemistry, demonstrated innervation by DiI-labeled axons of only parasympathetic postganglionic intramural ganglia in normal controls and sham operated controls, but reinnervation of both intramural ganglia and detrusor muscle directly after repair of sacral ventral roots. GF NT and CG NT also resulted in reinnervation of both intramural ganglia and detrusor muscle, although to a lesser extent than repaired roots. Bladder reinnervation with either the same nerve (orthotopic reinnervation) or with either a primarily somatic nerve (coccygeal) or a primarily sensory nerve (genitofemoral) results in reinnervation of both intramural ganglia as well as direct innervation of detrusor muscle.

A comparison between the effects of three potential scar-reducing agents applied at a site of sciatic nerve repair

A comparison between the effects of three potential scar-reducing agents applied at a site of sciatic nerve repair

A comparison between the effects of three potential scar-reducing agents applied at a site of sciatic nerve repair

A comparison between the effects of three potential scar-reducing agents applied at a site of sciatic nerve repair

Effect of Hyaluronic Acid-Carboxymethylcellulose Solution on Perineural Scar Formation after Sciatic Nerve Repair in Rats

BackgroundScar tissue formation is the major cause of failure in peripheral nerve surgery. Use of a hyaluronic acid-carboxymethylcellulose (HA-CMC) membrane (Seprafilm) as a solid anti-adhesion barrier agent is one of the therapeutic approaches to reduce postoperative scar tissue formation. However, a solid membrane may not be suitable for repair of a weak peripheral nerve site. This study examined the effect of HA-CMC solution on perineural scar formation after peripheral nerve repair in rats.MethodsThe sciatic nerves of 40 rats were transected and then immediately repaired using 10-0 nylon. The nerves were divided randomly into two groups. Saline and HA-CMC solution were applied topically to the nerve repair sites in the control and experimental groups, respectively. Reoperation was performed at 3, 6, 9, and 12 weeks to assess scar tissue formation. The assessment included the quality of wound healing, presence of perinueral adhesion, cellular components of the scar tissue, thickness of the scar tissue and histomorphological organization of the repair site.ResultsTopical application of the HA-CMC solution significantly decreased the macroscopic nerve adherence score and the numbers of the cellular components such as fibroblasts and inflammatory cells (p < 0.05, Mann-Whitney U-test). The scar tissue formation index was significantly lower in the experimental group at 12 weeks than that in the control group (p < 0.05, Mann-Whitney U-test). The grading scores of the histomorphological axonal organization at the repair site were significantly higher in the experimental group than those in the control group at 12 weeks (p < 0.05, Mann-Whitney U-test). No evidence of wound dehiscence or inflammatory reactions against the HA-CMC solution was noted.ConclusionsTopical application of a HA-CMC solution is effective in reducing the perineural scar formation and adhesion after sciatic nerve repair in rats, and is effective in promoting peripheral nerve regeneration at the repair site.

Improving electrophysiologic and histologic outcomes by photochemically sealing amnion to the peripheral nerve repair site

The surgical approach used today in the repair of peripheral nerve injuries rarely achieves full functional recovery. This study determines whether isolation of the nerve repair site using photochemical tissue bonding (PTB) in combination with human amniotic membrane can improve both functional and histologic recovery. New Zealand white rabbits (n = 24) underwent transection of the right common peroneal nerve. Epineural nerve repair was performed using 10-0 nylon sutures. The repair site was then wrapped in a cuff of human amniotic membrane, which either was secured with sutures or sealed using PTB. Standard neurorrhaphy alone was assessed as a control group. Functional recovery was recorded at 30-day intervals postoperatively by electrophysiologic assessment. At 120 days, animals were killed humanely and nerves harvested for histomorphometry. Nerves treated with amnion wraps and sealed with PTB demonstrated a statistically significant improvement across both functional and histologic parameters. Functional recovery, as measured by repeated electrophysiologic studies over time, revealed a 26.2% improvement over standard neurorrhaphy alone (P < .05). Nerves treated with PTB-sealed amnion wraps had significantly greater (P < .001) axon (5.08 +/- 1.06 microm) and fiber diameters (7.46 +/- 1.37 microm), as well as myelin thickness (2.39 +/- 0.7 microm) and the g ratio (axon diameter/fiber diameter ratio; 0.68 +/- 0.07) distal to the repair site compared to standard neurorrhaphy alone (4.98 +/- 1.81 microm, 6.77 +/- 1.94 microm, 1.79 +/- 0.42 microm, and 0.71 +/- 0.09, respectively). Isolation of the repair site using a photochemically sealed amnion wrap improves electrophysiologic and histologic recovery compared to standard suture neurorrhaphy.

Comparative Analysis of Biomechanical Performance of Available “Nerve Glues”

To compare a variety of potentially useful artificial and biological sealants applied to sutured nerve repairs to decrease gapping at the repaired site. Fifty-seven fresh-frozen cadaveric nerve specimens were transected and repaired with two 8-0 nylon epineural sutures placed 180 degrees apart. The specimens were divided into 5 groups. Four groups received augmentation of the repair with application of either autologous fibrin glue, Tisseel fibrin glue, Evicel fibrin glue, or DuraSeal polyethylene glycol-based hydrogel sealant, and the fifth group had no glue. Each nerve construct was mounted in a servohydraulic materials testing machine and stretched at a constant 5 mm/min displacement rate until failure. A noncontact video analysis permitted normalization of stretch within the repair region. Statistical analysis was performed via analysis of variance followed by Tukey-Kramer post hoc pairwise comparison when indicated. Resistance to gapping as measured through normalized stiffness (N/mm/mm) was greater for the Tisseel group, Evicel group, and DuraSeal group versus the no-glue group only. The stiffness of the autologous group approached significance versus the no-glue group. There were no significant differences in stiffness between any of the nerve glue groups. There was no statistical difference for the peak load at failure between any of the groups. Avoidance of gapping at the nerve repair site is crucial in achieving successful nerve regeneration. Commercially available tissue sealants (Tisseel, Evicel, and DuraSeal), when used to augment 2-suture nerve repairs, as in our protocol, help prevent this initial gapping. None of the tissue sealants tested, however, increased the ultimate load to complete failure of the repair.

Photochemical Sealing Improves Outcome Following Peripheral Neurorrhaphy

Peripheral nerve transection initiates a complex molecular response in the severed nerve endings, resulting in the release of neurotrophic and neurotropic factors that are central to axonal survival and regeneration. In this study we tested the hypothesis that sealing the neurorrhaphy site from the surrounding environment using a photochemically bonded nerve wrap would optimize the endoneural environment and enhance regeneration and nerve function recovery. Adult rats underwent unilateral sciatic nerve transection and standard epineural nerve repair. The repair site was wrapped with amniotic membrane or autologous vein and then was either sealed using photochemical tissue bonding (PTB) or secured with sutures. Photochemical sealing without a wrap was also carried out. Functional recovery was assessed at 2-wk intervals using walking track analysis and nerve histomorphometry was assessed at 12 wk. Treating nerves with PTB-sealed amnion significantly improved functional recovery and increased distal axon and fiber diameters and myelin thickness compared to nerves treated with standard neurorrhaphy alone. Direct PTB sealing of the repair site also improved function. Neither amnion secured with sutures nor vein wraps exhibited improved functional or histological recovery compared to standard neurorrhaphy. These results suggest that sealing the peripheral nerve repair site with amnion using a photochemical technique may lead to earlier restoration of neural homeostasis and consequent enhanced repair of nerve injury.

NERVE REGENERATION THROUGH NERVE AUTOGRAFTS AFTER LOCAL ADMINISTRATION OF BRAIN-DERIVED NEUROTROPHIC FACTOR WITH OSMOTIC PUMPS

To determine whether or not administration of brain-derived neurotrophic factor (BDNF) with osmotic pumps at the site of the proximal stump of a peripheral nerve autograft can improve peripheral nerve regeneration. The tibialis branch of the sciatic nerve was transected and grafted with a 20-mm nerve autograft. Wistar rats (Harlan iberica, Barcelona, Spain) (n = 70) were divided into four groups: a nongrafted control group (Group I, n = 10), a grafted but nontreated control group (Group II, n = 20), a grafted saline-treated group (Group III, n = 20), and a grafted and BDNF-treated group (Group IV, n = 20). BDNF was delivered at a rate of 6 microg/day for 2 weeks after nerve repair using osmotic pumps subcutaneously implanted with a connecting tube, the distal end of which faced the proximal stump of the nerve graft. The animals were euthanized at 6 weeks. Spinal motoneurons were quantified as well as axons at the tibialis branch 5 mm distal to the distal nerve repair site. Neuron size was categorized as large (>25 microm) or small (<25 microm). The statistical comparisons between the mean number of neurons in Groups II and III showed no statistical differences (P = 0.27), but there were statistically significant differences between Groups II and IV (P = 0.02) and III and IV (P = 0.02). Labeling of neurons in the group treated with BDNF represents 76% of neurons found on the nonoperated control Group I, which, in turn, is superior to the 51% of neurons found in the nontreated autograft Groups II and III. Regarding the size of motoneurons, there were no statistically significant differences between groups (P > 0.1). Finally, there were no statistically significant differences among Groups II, III, and IV regarding the number of distal axons. BDNF delivered through osmotic pumps was found to have a significant capacity for improving the presence of motoneurons in the ventral spinal horn and, thus, capacity to improve nerve regeneration through nerve autografts. However, in this study, BDNF did not specifically protect against injury to motoneurons, depending on the soma size.

Interleukin‐10 reduces scarring and enhances regeneration at a site of sciatic nerve repair

Axonal regeneration at a site of peripheral nerve repair can be impeded by the formation of scar tissue, which creates a mechanical barrier and initiates the development of multiple branched axonal sprouts that form a neuroma. We have investigated the hypothesis that the application of a scar-reducing agent to the nerve repair site would permit better axonal regeneration. In anaesthetised C57 Black-6 mice, the left sciatic nerve was sectioned and immediately re-approximated using four epineurial sutures. In five groups of eight mice, we injected transforming growth factor-beta3 (50 or 500 ng), interleukin-10 (IL-10) (125 or 500 ng), or saline into and around the repair site, both before and after the nerve section. Another group of eight animals acted as sham-operated controls. After 6 weeks, the outcome was assessed by recording compound action potentials (CAPs), measuring collagen levels using picrosirius red staining, and counting the number of myelinated axons proximal and distal to the repair. CAPs evoked by electrical stimulation distal to the repair were significantly smaller in all repair groups except for the low-dose IL-10 group, where they were not significantly different from that in controls. The area of staining for collagen had significantly increased in all repair groups except for the low-dose IL-10 group, which was not significantly different from that in controls. The myelinated fibre counts were always higher distal to the repair site, but there were no significant differences between groups. We conclude that administration of a low-dose of IL-10 to a site of sciatic nerve repair reduces scar formation and permits better regeneration of the damaged axons.

Comparative Study of Scar Formation at the Site of Sciatic Nerve Repair in Rats

Purpose : To investigate the effectiveness and to compare the degree of axonal regeneration with the control after the topical application of dexamethasone, hyaluronic acid and amniotic fluid at the repair site of the peripheral nerve. Materials and Methods : The left sciatic nerves of 40 adult Sprague-Dawley rats were transected and neurorrhaphy was performed. The nerves were divided into four groups according to thesolution applied around the repair site: control group (group 1), 0.3 ml normal saline: experimental groups, 0.3 ml dexamethasone (group 2), 0.3 ml hyaluronic acid (group 3), and 0.3 ml amniotic fluid (group 4). The thickness of the perineural scar tissue, the count of the myelinated nerve fiber and axonal regeneration on the repair site were evaluated electromyographically and histologically 4 and 12 weeks after surgery. Results : The peak amplitude of the compound motor action potential was observed in group 2, at postoperative 4 weeks and group 3 at postoperative 12 weeks. The increase in the number of myelinated nerve fibers was most prominently in group 3 at 4 and 12 weeks after surgery. The degree of perineural scarring was lowest in group 2 at postoperative 4 weeks and in group 3 at postoperative 12 weeks. Conclusion : A single dose topical application of Dexamethasone, HA and Amniotic fluid is more effective in preventing perineural scar formation as well as in facilitating the nerve regeneration process in a rat hind-limb model than using saline.

The effect of antibodies to TGF‐β1 and TGF‐β2 at a site of sciatic nerve repair

Scar formation at a site of nerve injury can cause a mechanical barrier to axonal regeneration and lead to the development of multiple axonal sprouts to form a neuroma. We have investigated the hypothesis that the application of a scar-preventing agent to a nerve repair site would enhance regeneration of the nerve and reduce neuroma formation. The left sciatic nerve was exposed under general anaesthesia in 18 adult Sprague-Dawley rats. In 12 animals, the nerve was sectioned and immediately re-approximated using four epineurial sutures, and in 6 of these animals neutralising antibodies to transforming growth factor (TGF)-beta1 and TGF-beta2 were injected into and around the repair site. The six other animals acted as controls. After 7 weeks, the outcome was assessed by recording compound action potential (CAP) ratios, measuring collagen levels using picrosirius red staining, and counting the number of myelinated axons proximal and distal to the repair. After repair alone, the mean percentage of area of staining (PAS) for collagen within the nerve had significantly increased. However, after repair with the administration of antibodies, the PAS was not significantly different from that in the sham controls. After administration of antibodies, the CAP ratios were significantly smaller than in controls but not after repair alone. In both nerve injury groups, the myelinated fibre counts were significantly increased distal to the injury site, but there was no difference between these two groups. We conclude that administration of antibodies to TGF-beta1 and TGF-beta2 reduced scar formation at the repair site but did not enhance regeneration of the nerve or reduce the development of multiple axonal sprouts.

Chondroitinase applied to peripheral nerve repair averts retrograde axonal regeneration

Antegrade, target-directed axonal regeneration is the explicit goal of nerve repair. However, aberrant and dysfunctional regrowth is commonly observed as well. At the site of surgical nerve coaptation, axonal sprouts encounter fibrotic connective tissue rich in growth-inhibiting chondroitin sulfate proteoglycan that may contribute to misdirection of axonal regrowth. In the present study, we tested the hypothesis that degradation of chondroitin sulfate proteoglycan by application of chondroitinase at the site of nerve repair can decrease aberrant axonal growth. Adult rats received bilateral sciatic nerve transection and end-to-end repair. One nerve was injected with chondroitinase ABC and the contralateral nerve treated with vehicle alone. After 28 weeks, retrograde axonal regeneration was assessed proximal to the repair by scoring neurofilament-immunopositive axons within the nerve (intrafascicular) and outside the nerve proper (extrafascicular). Intrafascicular retrograde axonal growth was equivalent in both control and chondroitinase treatment conditions. In contrast, chondroitinase treatment caused a pronounced (93%) reduction in extrafascicular retrograde axonal growth. The decrease in axon egress from the nerve was coincident with an increase in antegrade regeneration and improved recovery of motor function. Based on these findings, we conclude that chondroitinase applied at the site of nerve transection repair averts dysfunctional extrafascicular retrograde axonal growth.

Scarring impedes regeneration at sites of peripheral nerve repair

We have investigated the effect of scarring at a site of peripheral nerve repair by comparing regeneration of the sciatic nerve in normal mice and two transgenic strains with an increased or decreased propensity for scarring. The outcome was assessed by quantifying collagen at the repair site, recording compound action potentials and counting myelinated nerve fibres on each side of the repair. We found that higher levels of collagen scar formation were associated with smaller compound action potentials, slower conduction velocities and a reduction in fibre numbers across the repair site. We conclude that scarring impedes regeneration at sites of nerve repair and suggest that this could be amenable to therapeutic manipulation.

Photochemical Sealing of Microsurgical Neurorrhaphy Improves Functional Recovery

Intraneural scarring adversely affects the clinical outcome following microsurgical repair of peripheral nerve injury. The aim of this study was to determine if isolation of the nerve repair site using photochemical tissue bonding (PTB) in combination with a sleeve of autologous vein or human amniotic membrane could exclude ingrowth of fibrotic tissue and improve functional recovery.

Effects of alleviated tension at the nerve repair site using biodegradable tubular conduits: Histological, electrophysiological and functional results in a rat model

BACKGROUND: The effect of mobilization on the functional regeneration of peripheral nerves remains controversial. Functional efficacy of alleviated tension at the nerve repair site in a full range of motion model in the rat was recently published elsewhere. This study sought to determine the effect of alleviated tension at the nerve repair site using biodegradable tubular conduits for segmental nerve splinting to block, thereby blocking variable tension. METHODS: In 60 rats, the right sciatic nerve was transected midthigh and coapted immediately microsurgically. The animals were divided into four groups. Group N, epineural nerve repair (control). For the groups listed below, segmental tubular nerve splinting with alleviated in situ tension at the nerve suture site was performed using tubular conduits of different biodegradable materials. Polyurethane group, biodegradable polyurethane tubular conduits. Neuragen group, collagen I tubular conduits. Neurolac group: DL-lactide-e-caprolactone tubular conduits. Full range of motion of lower limbs was ensured by passive motion of hind limbs once a week after functional testing. Histological and electrophysiological assessment and 12 postoperative weekly function tests (toe spread test and BBB Locomotor Rating Scale) were carried out. RESULTS: Functional results were significantly better in all groups using segmental biodegradable tubular nerve splinting for alleviated in situ tension at the nerve repair site, mainly because of less endoneural scar formation at the nerve suture segment. However, this effect was attenuated when polyurethane tubular conduits were used. Electrophysiologic results showed increased amplitude and compound nerve action potential area in the alleviated tension groups. Nerve conduction velocity was fastest in the Neuragen group. CONCLUSIONS: Complete alleviation of in situ tension at the nerve suture site with biodegradable tubular conduits seems to improve functional peripheral nerve regeneration by significant decrease of endoneural collagenization in the nerve suture segment. Additionally, our findings suggest that alleviated tension in the nerve suture segment using biodegradable conduits depends upon which material is used.

The effect of brain-derived neurotrophic factor on sensory and autonomic function after lingual nerve repair

Brain-derived neurotrophic factor (BDNF) is important in the response to peripheral nerve injury and may enhance regeneration. We have assessed its role in the functional recovery of sensory afferents and autonomic efferents after repair of the chorda tympani and lingual nerves in the cat. Six months after entubulation repair, with or without the incorporation of BDNF at the repair site, the recovery of secretomotor and vasomotor efferents was determined by recording salivary flow from the submandibular gland and temperature changes on the tongue surface, each evoked by stimulation of the repaired nerve. Electrophysiological recordings from the lingual and chorda tympani nerves proximal to the repair were undertaken to characterise mechanosensitive, thermosensitive, and gustatory afferents. When compared with data from uninjured control animals, both repair groups showed changes in receptor sensitivity and spontaneous discharge, and persistent reductions in conduction velocity, proportion of gustatory and thermosensitive units, rate of salivary secretion, and vasomotor responses. Comparisons between the outcome of repair with or without BDNF revealed few differences. In the BDNF group, fewer units in the chorda tympani responded to gustatory or thermal stimuli and the sensitivity of the gustatory units was lower. The conduction velocity of afferents in the lingual nerve was also lower, but the mechanoreceptive field size was higher. Thus, despite its known trophic role in the gustatory system, BDNF had not enhanced recovery of these or other fibre populations. We conclude that the application of BDNF to a site of lingual nerve repair has a negative effect on the long-term outcome.